Clinical Trial Results:
A Phase 1b/2 Randomized Study of MEDI-575 in Combination With Carboplatin Plus Paclitaxel Versus Carboplatin Plus Paclitaxel Alone in Adult Subjects With Previously Untreated, Advanced Non-Small Cell Lung Cancer
Summary
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EudraCT number |
2010-023854-35 |
Trial protocol |
DE HU BG |
Global end of trial date |
04 Sep 2013
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Results information
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Results version number |
v2(current) |
This version publication date |
20 Dec 2020
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First version publication date |
23 Jun 2016
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Other versions |
v1 |
Version creation reason |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CD-ON-MEDI-575-1031
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01268059 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
MedImmune, LLC
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Sponsor organisation address |
One MedImmune Way, Gaithersburg, United States, 20878
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Public contact |
Mohammed Dar, MD, Vice President & Head, Clinical Development, Oncology, MedImmune, LLC, +1 301-398-0000, information.center@astrazeneca.com
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Scientific contact |
Mohammed Dar, MD, Vice President & Head, Clinical Development, Oncology, MedImmune, LLC, +1 301-398-0000, information.center@astrazeneca.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
04 Sep 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Sep 2013
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
For phase 1b, main objective was evaluation of the safety profile of MEDI-575 when used in combination with carboplatin/paclitaxel in participants with previously untreated, advanced non-small cell lung cancer (NSCLC). For phase 2, main objective was evaluation of progression-free survival of subjects following treatment with MEDI-575 when used in combination with paclitaxel/carboplatin versus paclitaxel/carboplatin alone in participants with previously untreated, advanced NSCLC.
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Participating participant signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Dec 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 64
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Country: Number of subjects enrolled |
France: 3
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Country: Number of subjects enrolled |
Poland: 5
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Country: Number of subjects enrolled |
Canada: 12
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Country: Number of subjects enrolled |
Hungary: 1
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Country: Number of subjects enrolled |
Japan: 14
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Worldwide total number of subjects |
99
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EEA total number of subjects |
9
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
50
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From 65 to 84 years |
49
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Overall, 99 participants were enrolled in study, (4 participants, all from North America sites, were enrolled in Phase 1b and 95 participants in Phase 2 of study). Of 95 participants, 14 were from Japan, 81 were from North American and European Union (EU) sites. End of study is 14 months from last participant enrolled, or sponsor stopped study. | ||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Carboplatin/Paclitaxel (C/P): North America/EU Population | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Carboplatin/paclitaxel regimen (carboplatin area under the plasma concentration-time curve [AUC] of 6 milligram per milliliter into minute [mg/mL*min], and paclitaxel 200 milligram per square meter [mg/m^2]) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) or until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Carboplatin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Carboplatin 6 milligram per milliliter into minute [mg/mL*min] once every 21 days on Day 1, for a total of 6 doses (cycles).
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Investigational medicinal product name |
Paclitaxel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Paclitaxel 200 milligram per square meter [mg/m^2] once every 21 days on Day 1, for a total of 6 doses (cycles).
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Arm title
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C/P + MEDI-575 (C/P/M): North America/EU Population | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles. Participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575, MEDI-575 alone was continued until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MEDI-575
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intracavernous use
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Dosage and administration details |
MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) once every 21 days on Day 1 for a total of 6 cycles.
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Investigational medicinal product name |
Carboplatin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Carboplatin 6 milligram per milliliter into minute [mg/mL*min] once every 21 days on Day 1, for a total of 6 doses (cycles).
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Investigational medicinal product name |
Paclitaxel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Paclitaxel 200 milligram per square meter [mg/m^2] once every 21 days on Day 1, for a total of 6 doses (cycles).
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Arm title
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Carboplatin/Paclitaxel (C/P): Japan Population | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) administered as an IV infusion once every 21 days on Day 1, for a total of 6 doses (cycles) or until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Carboplatin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Carboplatin 6 milligram per milliliter into minute [mg/mL*min] once every 21 days on Day 1, for a total of 6 doses (cycles).
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Investigational medicinal product name |
Paclitaxel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Paclitaxel 200 milligram per square meter [mg/m^2] once every 21 days on Day 1, for a total of 6 doses (cycles).
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Arm title
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C/P + MEDI-575 (C/P/M): Japan Population | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles. Participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575, MEDI-575 alone was continued until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MEDI-575
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intracavernous use
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Dosage and administration details |
MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) once every 21 days on Day 1 for a total of 6 cycles.
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Investigational medicinal product name |
Carboplatin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Carboplatin 6 milligram per milliliter into minute [mg/mL*min] once every 21 days on Day 1, for a total of 6 doses (cycles).
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Investigational medicinal product name |
Paclitaxel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Paclitaxel 200 milligram per square meter [mg/m^2] once every 21 days on Day 1, for a total of 6 doses (cycles).
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Baseline characteristics reporting groups
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Reporting group title |
Carboplatin/Paclitaxel (C/P): North America/EU Population
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Reporting group description |
Carboplatin/paclitaxel regimen (carboplatin area under the plasma concentration-time curve [AUC] of 6 milligram per milliliter into minute [mg/mL*min], and paclitaxel 200 milligram per square meter [mg/m^2]) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) or until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
C/P + MEDI-575 (C/P/M): North America/EU Population
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Reporting group description |
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles. Participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575, MEDI-575 alone was continued until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Carboplatin/Paclitaxel (C/P): Japan Population
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Reporting group description |
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) administered as an IV infusion once every 21 days on Day 1, for a total of 6 doses (cycles) or until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
C/P + MEDI-575 (C/P/M): Japan Population
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Reporting group description |
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles. Participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575, MEDI-575 alone was continued until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Carboplatin/Paclitaxel (C/P): North America/EU Population
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Reporting group description |
Carboplatin/paclitaxel regimen (carboplatin area under the plasma concentration-time curve [AUC] of 6 milligram per milliliter into minute [mg/mL*min], and paclitaxel 200 milligram per square meter [mg/m^2]) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) or until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. | ||
Reporting group title |
C/P + MEDI-575 (C/P/M): North America/EU Population
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Reporting group description |
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles. Participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575, MEDI-575 alone was continued until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. | ||
Reporting group title |
Carboplatin/Paclitaxel (C/P): Japan Population
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Reporting group description |
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) administered as an IV infusion once every 21 days on Day 1, for a total of 6 doses (cycles) or until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. | ||
Reporting group title |
C/P + MEDI-575 (C/P/M): Japan Population
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Reporting group description |
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles. Participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575, MEDI-575 alone was continued until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. | ||
Subject analysis set title |
Carboplatin/Paclitaxel (Total)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Carboplatin/paclitaxel regimen (carboplatin area under the plasma concentration-time curve [AUC] of 6 milligram per milliliter into minute [mg/mL*min], and paclitaxel 200 milligram per square meter [mg/m^2]) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) or until unacceptable toxicity, disease progression, or other reasons for participant withdrawal.
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Subject analysis set title |
Carboplatin/Paclitaxel + MEDI-575 (Total)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles. Participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575, MEDI-575 alone was continued until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal.
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Subject analysis set title |
Carboplatin/Paclitaxel + MEDI-575 - Phase 1b
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles. Participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575, MEDI-575 alone was continued until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal.
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Subject analysis set title |
Carboplatin/Paclitaxel + MEDI-575 - Phase 2
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles. Participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575, MEDI-575 alone was continued until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal.
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Subject analysis set title |
Carboplatin/Paclitaxel - Phase 2
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Carboplatin/paclitaxel regimen (carboplatin area under the plasma concentration-time curve [AUC] of 6 milligram per milliliter into minute [mg/mL*min], and paclitaxel 200 milligram per square meter [mg/m^2]) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) or until unacceptable toxicity, disease progression, or other reasons for participant withdrawal.
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End point title |
Number of Participants With Dose Limiting Toxicities (DLT): Phase 1b [1] | ||||||
End point description |
A DLT was defined as: 1. Any treatment-related Grade 3 or higher non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions: a. Grade 3 fever (in the absence of neutropenia) defined as more than (>) 40.0 degree Celcius (> 104.0 degree Fahrenheit) that resolved to normal or baseline within 24 hours of treatment and was not considered a serious adverse event (SAE); or b. Grade 3 rigors/chills that responded to optimal therapy. 2. Any treatment-related Grade 3 or higher hematologic toxicity. The evaluable population for dose determination included all participants who were in Phase 1b, received at least 1 full cycle of MEDI-575 and completed the safety follow-up through the DLT evaluation period or participants who experienced any DLT.
|
||||||
End point type |
Primary
|
||||||
End point timeframe |
From Day 1 to Day 21 of first cycle
|
||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point. As listed in the table, there were 4 subjects dosed and analyzed and 0 experienced a DLT. |
|||||||
|
|||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Progression Free-Survival (PFS) [2] | ||||||||||||
End point description |
Progression-free survival defined as the time from randomization (randomization referred to the date of treatment assignment) to disease progression (defined according to Response Evaluation Criteria for Solid Tumors [RECIST] guidelines) or death due to any cause, whichever occurs first. Participants without progression or death at the time of analysis were censored at their last date of tumor evaluation. PFS was assessed only in North America/European Union (EU) participants. The Intent-to-Treat (ITT) North America/EU population included all North America/EU participants who were randomized into Phase 2 portion of the study.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
From randomization until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
|
||||||||||||
Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only those baseline period arms for which analysis was planned were reported in the end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
PFS | ||||||||||||
Statistical analysis description |
Progression-free Survival (ITT Phase 2 North America/EU Population) for Carboplatin/Paclitaxel + MEDI-575 versus Carboplatin/Paclitaxel
|
||||||||||||
Comparison groups |
Carboplatin/Paclitaxel (C/P): North America/EU Population v C/P + MEDI-575 (C/P/M): North America/EU Population
|
||||||||||||
Number of subjects included in analysis |
46
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [3] | ||||||||||||
P-value |
= 0.027 [4] | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
2.205
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.1 | ||||||||||||
upper limit |
4.5 | ||||||||||||
Notes [3] - Hazard ratio and its 95 percent (%) confidence interval ( CIs) were calculated using the Cox proportional hazard model stratified by histology, disease stage, and Eastern Cooperative Oncology Group (ECOG) performance status. [4] - The 2-sided p-value was calculated using the log-rank test stratified by histology, disease stage, and ECOG performance status. |
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Best Overall Response | ||||||||||||||||||||||||||||||||||||||||
End point description |
Best overall response of a participant was defined as the best tumor response [Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)] observed during the trial period assessed according to the RECIST version 1.1 criteria. The participant’s best overall response assignment depended on the findings of both target and non-target disease and also on the appearance of new lesions. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30 percent (%) in the sum of diameters of target lesion, SD was defined as steady state of disease, and PD was defined as an increase of at least 20% in the sum of diameters of target lesions. The ITT North America/EU population included all North America/EU participants who were randomized into Phase 2 portion of the study. The ITT Japanese population included all Japanese participants who were randomized into the Phase 2 portion of the study.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Objective Response Rate (ORR) | ||||||||||||||||||||
End point description |
The ORR defined as the percentage of participants with confirmed CR or confirmed PR according to RECIST guidelines. Confirmed responses were those that persist on repeat imaging or assessment greater than or equal to (>=) 4 weeks after the initial documentation of response. The ITT North America/EU population included all North America/EU participants who were randomized into Phase 2 portion of the study. The ITT Japanese population included all Japanese participants who were randomized into the Phase 2 portion of the study.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
ORR (North America/EU) | ||||||||||||||||||||
Statistical analysis description |
Objective Response Rate Comparision for Carboplatin/Paclitaxel + MEDI-575 versus Carboplatin/Paclitaxel.
|
||||||||||||||||||||
Comparison groups |
Carboplatin/Paclitaxel (C/P): North America/EU Population v C/P + MEDI-575 (C/P/M): North America/EU Population
|
||||||||||||||||||||
Number of subjects included in analysis |
81
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.487 [5] | ||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [5] - The 2-sided p-value was calculated by adjusting for the stratification factors histology, disease stage, and Eastern Cooperative Oncology Group (ECOG) performance status. |
|||||||||||||||||||||
Statistical analysis title |
ORR (Japan) | ||||||||||||||||||||
Statistical analysis description |
Treatment effect Carboplatin/Paclitaxel + MEDI-575 versus Carboplatin/Paclitaxel.
|
||||||||||||||||||||
Comparison groups |
Carboplatin/Paclitaxel (C/P): Japan Population v C/P + MEDI-575 (C/P/M): Japan Population
|
||||||||||||||||||||
Number of subjects included in analysis |
14
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||
P-value |
= 0.386 [6] | ||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [6] - The 2-sided p-value was calculated by adjusting for the stratification factors histology, disease stage, and ECOG performance status. |
|
|||||||||||||||||||||
End point title |
Time to Response (TTR) | ||||||||||||||||||||
End point description |
TTR was measured from randomization to the first documentation of objective response and assessed only in participants who achieved objective response. The ORR defined as the percentage of participants with confirmed CR or confirmed PR according to RECIST guidelines. Confirmed responses were those that persist on repeat imaging or assessment >=4 weeks after the initial documentation of response. The ITT North America/EU population included all North America/EU participants who were randomized into Phase 2 portion of the study. The ITT Japanese population included all Japanese participants who were randomized into the Phase 2 portion of the study. Participants who achieved OR were analyzed for this outcome measure. In the below table 0.9999 and 99999 indicates that the 95% confidence interval was not estimated because only 1 participant had OR in the specified arm.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Duration of Response (DR) | ||||||||||||||||||||
End point description |
The DR defined as the duration from the first documentation of objective response to the first documented disease progression. Participants without progression at the time of analysis were censored at their last date of tumor evaluation. The ITT North America/EU population included all North America/EU participants who were randomized into Phase 2 portion of the study. The ITT Japanese population included all Japanese participants who were randomized into the Phase 2 portion of the study. Participants who achieved OR were analyzed for this outcome measure. In the below table 0.9999 and 99999 indicates the 95% confidence interval was not estimated because only 1 participants had OR in the specified arm.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Time to Progression (TTP) | ||||||||||||||||||||
End point description |
The TTP was measured from randomization until the documentation of disease progression. Disease progression defined according to RECIST v 1.1 guidelines. Participants without progression at the time of analysis were censored at their last date of tumor evaluation. The ITT North America/EU population included all North America/EU participants who were randomized into Phase 2 portion of the study. The ITT Japanese population included all Japanese participants who were randomized into the Phase 2 portion of the study. The TTP was analyzed for only those participants who had disease progression.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
TTP (North America/EU) | ||||||||||||||||||||
Comparison groups |
Carboplatin/Paclitaxel (C/P): North America/EU Population v C/P + MEDI-575 (C/P/M): North America/EU Population
|
||||||||||||||||||||
Number of subjects included in analysis |
36
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||||||
Point estimate |
3.017
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
1.2 | ||||||||||||||||||||
upper limit |
7.4 | ||||||||||||||||||||
Statistical analysis title |
TTP (Japan) | ||||||||||||||||||||
Comparison groups |
Carboplatin/Paclitaxel (C/P): Japan Population v C/P + MEDI-575 (C/P/M): Japan Population
|
||||||||||||||||||||
Number of subjects included in analysis |
11
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||||||
Point estimate |
1.134
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.3 | ||||||||||||||||||||
upper limit |
4.3 |
|
|||||||||||||||||||||
End point title |
Overall Survival (OS) | ||||||||||||||||||||
End point description |
Overall survival defined as the time from randomization until death due to any cause. Participants who were still alive at the time of analysis were censored at their last date of last contact. In the below table 99999 indicates that median and confidence interval were not determined as an insufficient number of participants had the event. The ITT North America/EU population included all North America/EU participants who were randomized into Phase 2 portion of the study. The ITT Japanese population included all Japanese participants who were randomized into the Phase 2 portion of the study.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
OS (North America/EU) | ||||||||||||||||||||
Comparison groups |
Carboplatin/Paclitaxel (C/P): North America/EU Population v C/P + MEDI-575 (C/P/M): North America/EU Population
|
||||||||||||||||||||
Number of subjects included in analysis |
47
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||||||
Point estimate |
1.315
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.7 | ||||||||||||||||||||
upper limit |
2.4 | ||||||||||||||||||||
Statistical analysis title |
OS (Japan) | ||||||||||||||||||||
Comparison groups |
Carboplatin/Paclitaxel (C/P): Japan Population v C/P + MEDI-575 (C/P/M): Japan Population
|
||||||||||||||||||||
Number of subjects included in analysis |
8
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||||||
Point estimate |
2.083
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.4 | ||||||||||||||||||||
upper limit |
10.8 |
|
||||||||||||||||
End point title |
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | |||||||||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The safety population included all participants who received at least one dose of study drug.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants With Abnormalities in Laboratory Investigations Reported as Adverse Events (AEs) or Serious Adverse Events (SAEs) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Laboratory investigations included hematology, coagulation, serum chemistry and urinalysis parameters. Participants with abnormalities in these laboratory investigations recorded as AEs or SAEs were reported. The safety population included all participants who received at least one dose of study drug.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs | ||||||||||||||||||||||||
End point description |
The 12-lead ECG data were performed and obtained in triplicate that is 3 ECGs obtained within a 5 minute time period. Number of participants with ECG abnormalities were reported and recorded as AEs. The safety population included all participants who received at least one dose of study drug.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Maximum Observed Serum Concentration (Cmax) for MEDI-575 After First Dose | ||||||||||||
End point description |
The Cmax refers to the highest measured drug concentration after a single dose which is obtained by collecting a series of blood samples and average of measuring the concentrations of drug in each sample. Participants who were treated with MEDI-575 and for whom serum concentrations were available for PK data analyses.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time of Maximal Observed Concentration (Tmax) for MEDI-575 After First Dose | ||||||||||||
End point description |
The tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and average of measuring them for drug content. Participants who were treated with MEDI-575 and for whom serum concentrations were available for PK data analyses.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau) for MEDI-575 After First Dose | ||||||||||||
End point description |
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and average of measuring the concentrations of drug in each sample. AUCtau defined as area under the plasma concentration time profile from time zero to the end of the dosing interval (tau). Participants who were treated with MEDI-575 and for whom serum concentrations were available for PK data analyses.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Maximum Serum Concentration at Steady State (Cmax,ss) for MEDI-575 After First Dose | ||||||||||||
End point description |
Maximum serum concentration at steady state for MEDI-575 after first dose was calculated. Participants who were treated with MEDI-575 and for whom serum concentrations were available for PK data analyses.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time to Maximum Serum Concentration at Steady State (Tmax,ss) for MEDI-575 After First Dose | ||||||||||||
End point description |
Time to maximum serum concentration at steady state for MEDI-575 after first dose was calculated. Participants who were treated with MEDI-575 and for whom serum concentrations were available for PK data analyses.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Trough Serum Concentration at Steady State (Ctrough,ss) for MEDI-575 After First Dose | ||||||||||||
End point description |
Trough serum concentration at steady state for MEDI-575 after first dose was calculated. Participants who were treated with MEDI-575 and for whom serum concentrations were available for PK data analyses.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With Positive Anti-MEDI-575 Antibodies | ||||||||||||
End point description |
Immunogenicity assessment included determination of anti-drug (MEDI-575) antibodies in serum samples. The evaluable population included all participants who were treated with MEDI-575 and for whom at least one serum sample for immunogenicity testing was available.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 1 (prior to infusion) of Cycles 1 to 7 (21-day cycle), end of treatment, 30 and 60 days after the last dose (approximately 3 years)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The immunohistochemical expression of PDGFRα in tumor cells in archived formalin-fixed paraffin-embedded tissue samples collected at baseline are reported. The transmembrane receptor tyrosine kinase PDGFRα plays an important role in human carcinogenesis, both as a direct target on tumor cells and also as a mediator of stromal support for cancer cell growth. The data of positive-staining tumor cells are reported in 3 categories: intensity (1+ [weak expression, staining in <5 % of tumor cells]; 2+ [moderate expression, staining in >= 5 % of tumor cells]; and 3+ [strong expression, staining in >5 % of the tumor cells]), localization (membranous, cytoplasmic, or nuclear), and frequency (rare, occasional, or frequent). Evaluable populations for PDGFRα expression included all randomized participants who had formalin-fixed paraffin-embedded samples available at baseline and had positive-staining for tumor cells.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Screening [Days -28 to -1])
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The immunohistochemical expression of PDGFRα in stromal cells in archived formalin-fixed paraffin-embedded tissue samples collected at baseline are reported. The transmembrane receptor tyrosine kinase PDGFRα plays an important role in human carcinogenesis, both as a direct target on tumor cells and also as a mediator of stromal support for cancer cell growth. The data of positive-staining stromal cells are reported in 3 categories: intensity (1+ [weak expression, staining in <5 % of tumor cells]; 2+ [moderate expression, staining in >= 5 % of tumor cells]; and 3+ [strong expression, staining in >5 % of the tumor cells]), localization (membranous, cytoplasmic, or nuclear), and frequency (rare, occasional, or frequent). Evaluable populations for PDGFRα expression included all randomized participants who had formalin-fixed paraffin-embedded samples available at baseline and had positive-staining for tumor cells.
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End point type |
Secondary
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End point timeframe |
Baseline (Screening [Days -28 to -1])
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Carboplatin/Paclitaxel (Total)
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Reporting group description |
Carboplatin/paclitaxel regimen (carboplatin area under the plasma concentration-time curve [AUC] of 6 milligram per milliliter into minute [mg/mL*min], and paclitaxel 200 milligram per square meter [mg/m^2]) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) or until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Carboplatin/Paclitaxel + MEDI-575 (Total)
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Reporting group description |
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles. Participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575, MEDI-575 alone was continued until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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16 Dec 2010 |
The protocol was amended for the modification of sample size and defining cohorts, participating sites were increased in Japanese sites, randomization criteria in North America/EU cohort and Japanese cohort were defined, clarification was provided for a cap on squamous cell histology and if subject experiences dose-limiting toxicity (DLT) due to MEDI-575 in the first 21-day cycle were provided, safety reporting procedures in Japan were added, inclusion and exclusion criteria were revised, information regarding the potential for a drug-drug interaction with CYP2C8 and CYP3A4 inhibitors and inducers (per the approved labeling for paclitaxel) was added, , updated population analysis definitions, clarifications for the administration of carboplatin/paclitaxel and MEDI-575 and analyses methods for objective response rate (ORR) and change in tumor size were included and confirmed that primary endpoint of progression-free survival (PFS) would only be in the North America/EU cohort. |
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10 Feb 2012 |
The protocol was amended for the modification of inclusion and withdrawal criteria, treatment administration, storage, and handling details were added, Preparation of Investigational Product at the site was updated (once prepared, MEDI-575 had to be used within 6 hours or discarded as it does not contain a preservative), Safety follow-up post last dose was increased from 60 to 90 days, and Data Safety Monitoring Board was added. |
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09 May 2012 |
The protocol was amended to remove primary endpoint of progression-free survival (PFS) as reference to a blinded central review of imaging data, NSCLC histology was removed as a stratification factor, MEDI-575 serum concentration and ADA assessments were removed from the 3-month post last treatment visit, Subgroup analysis for each NSCLC histology type was changed to be performed for each of the antitumor activity endpoints (PFS, ORR, DR, TTP, TTR, and OS) and Inclusion Criterion was revised. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
In conjunction with the overall risk-benefit assessment, study was terminated prematurely due to safety concerns. Change in tumor size outcome measure was not analyzed as per changed planned analysis due to premature termination of the study. |