Clinical Trial Results:
A Randomized, Phase II, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Onartuzumab (MetMAb) in Combination With Paclitaxel + Cisplatin or Carboplatin as First-Line Treatment for Patients With Stage IIIB (T4 Disease) or IV Squamous Non-Small Cell Lung Cancer (NSCLC)
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Summary
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EudraCT number |
2011-003720-12 |
Trial protocol |
DE GB LV ES IT |
Global end of trial date |
02 Sep 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Sep 2016
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First version publication date |
17 Sep 2016
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Other versions |
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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 |
GO27820
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01519804 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.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 |
02 Sep 2015
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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 |
02 Sep 2015
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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 |
This was a randomized, Phase II, multicenter, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of onartuzumab in combination with paclitaxel + platinum relative to treatment with placebo + paclitaxel + platinum in participants with incurable Stage IIIB (T4 disease) or Stage IV squamous non-small cell lung cancer (NSCLC) in the first-line setting.
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Protection of trial subjects |
The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice (GCP) standards and according to the all local laws and regulations concerning clinical study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Apr 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Spain: 11
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Country: Number of subjects enrolled |
United Kingdom: 3
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Country: Number of subjects enrolled |
France: 4
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Country: Number of subjects enrolled |
Germany: 13
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Country: Number of subjects enrolled |
Italy: 6
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Country: Number of subjects enrolled |
Latvia: 16
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Country: Number of subjects enrolled |
Argentina: 3
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Country: Number of subjects enrolled |
Israel: 4
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Country: Number of subjects enrolled |
United States: 49
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Worldwide total number of subjects |
109
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EEA total number of subjects |
53
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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) |
43
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From 65 to 84 years |
66
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Screening tests and evaluations were performed within 28 days prior to Day 1. | ||||||||||||||||||||||||
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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 |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Onartuzumab + Paclitaxel + Cisplatin/Carboplatin | ||||||||||||||||||||||||
Arm description |
Onartuzumab was administered in the clinic on Day 1 of each 21-day cycle, up to 4 cycles during induction treatment; if there was no disease progression, maintenance therapy continued until disease progression, unacceptable toxicity, or death, whichever event occurred first. The individual dose of onartuzumab for each participant was 15 milligrams per kilogram (mg/kg) in 250 cubic centimeter (cc) final 0.9 percent (%) normal saline solution (NSS). Paclitaxel was administered IV at a dose of 200 milligrams per meter square (mg/m^2) over 3 hours after the completion of the onartuzumab infusion followed by platinum (cisplatin or carboplatin) every 21 days up to 4 cycles. Cisplatin IV infusion was administered 30 minutes after completion of the paclitaxel infusion at a dose of 75 mg/m^2 over 1 − 2 hours every 21 days up to 4 cycles or per standard of care at the institution or carboplatin (area under the curve [AUC] 6 mg/mL/min IV) every 21 days up to 4 cycles. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Onartuzumab
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Investigational medicinal product code |
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Other name |
MetMAb
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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 |
Onartuzumab was administered in the clinic on Day 1 of each 21-day cycle. The individual dose of onartuzumab for each participant was 15 mg/kg in 250 cc final 0.9% NSS.
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Arm title
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Placebo + Paclitaxel + Cisplatin/Carboplatin | ||||||||||||||||||||||||
Arm description |
Placebo matched to onartuzumab was administered in the clinic on Day 1 of each 21-day cycle. Paclitaxel was administered IV at a dose of 200 mg/m^2 over 3 hours after the completion of the placebo infusion followed by platinum (cisplatin or carboplatin). Cisplatin IV infusion was administered 30 minutes after completion of the paclitaxel infusion at a dose of 75 mg/m^2 over 1 − 2 hours every 21 days up to 4 cycles or per standard of care at the institution or carboplatin (AUC 6 mg/mL/min IV) every 21 days up to 4 cycles. | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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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 |
Placebo matched to onartuzumab was administered in the clinic on Day 1 of each 21-day cycle.
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Baseline characteristics reporting groups
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Reporting group title |
Onartuzumab + Paclitaxel + Cisplatin/Carboplatin
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Reporting group description |
Onartuzumab was administered in the clinic on Day 1 of each 21-day cycle, up to 4 cycles during induction treatment; if there was no disease progression, maintenance therapy continued until disease progression, unacceptable toxicity, or death, whichever event occurred first. The individual dose of onartuzumab for each participant was 15 milligrams per kilogram (mg/kg) in 250 cubic centimeter (cc) final 0.9 percent (%) normal saline solution (NSS). Paclitaxel was administered IV at a dose of 200 milligrams per meter square (mg/m^2) over 3 hours after the completion of the onartuzumab infusion followed by platinum (cisplatin or carboplatin) every 21 days up to 4 cycles. Cisplatin IV infusion was administered 30 minutes after completion of the paclitaxel infusion at a dose of 75 mg/m^2 over 1 − 2 hours every 21 days up to 4 cycles or per standard of care at the institution or carboplatin (area under the curve [AUC] 6 mg/mL/min IV) every 21 days up to 4 cycles. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo + Paclitaxel + Cisplatin/Carboplatin
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Reporting group description |
Placebo matched to onartuzumab was administered in the clinic on Day 1 of each 21-day cycle. Paclitaxel was administered IV at a dose of 200 mg/m^2 over 3 hours after the completion of the placebo infusion followed by platinum (cisplatin or carboplatin). Cisplatin IV infusion was administered 30 minutes after completion of the paclitaxel infusion at a dose of 75 mg/m^2 over 1 − 2 hours every 21 days up to 4 cycles or per standard of care at the institution or carboplatin (AUC 6 mg/mL/min IV) every 21 days up to 4 cycles. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Onartuzumab + Paclitaxel + Cisplatin/Carboplatin
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Reporting group description |
Onartuzumab was administered in the clinic on Day 1 of each 21-day cycle, up to 4 cycles during induction treatment; if there was no disease progression, maintenance therapy continued until disease progression, unacceptable toxicity, or death, whichever event occurred first. The individual dose of onartuzumab for each participant was 15 milligrams per kilogram (mg/kg) in 250 cubic centimeter (cc) final 0.9 percent (%) normal saline solution (NSS). Paclitaxel was administered IV at a dose of 200 milligrams per meter square (mg/m^2) over 3 hours after the completion of the onartuzumab infusion followed by platinum (cisplatin or carboplatin) every 21 days up to 4 cycles. Cisplatin IV infusion was administered 30 minutes after completion of the paclitaxel infusion at a dose of 75 mg/m^2 over 1 − 2 hours every 21 days up to 4 cycles or per standard of care at the institution or carboplatin (area under the curve [AUC] 6 mg/mL/min IV) every 21 days up to 4 cycles. | ||
Reporting group title |
Placebo + Paclitaxel + Cisplatin/Carboplatin
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Reporting group description |
Placebo matched to onartuzumab was administered in the clinic on Day 1 of each 21-day cycle. Paclitaxel was administered IV at a dose of 200 mg/m^2 over 3 hours after the completion of the placebo infusion followed by platinum (cisplatin or carboplatin). Cisplatin IV infusion was administered 30 minutes after completion of the paclitaxel infusion at a dose of 75 mg/m^2 over 1 − 2 hours every 21 days up to 4 cycles or per standard of care at the institution or carboplatin (AUC 6 mg/mL/min IV) every 21 days up to 4 cycles. | ||
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End point title |
Progression-Free Survival (PFS) [1] | ||||||||||||
End point description |
PFS is defined as the time between date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment with use of Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. PFS was to be estimated using Kaplan-Meier method. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (the appearance of one or more new lesions is also considered progression).
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End point type |
Primary
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End point timeframe |
Baseline, every 6 weeks (±7 days) during the first 4 cycles (each cycle was 21 days) of treatment, then every 9 weeks (±7 days) during the maintenance treatment until disease progression or death (maximum up to approximately 32 months)
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| 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: Endpoint was not evaluated due to early study termination primarily because of limited efficacy. |
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| Notes [2] - Endpoint was not evaluated due to early study termination primarily because of limited efficacy. [3] - Endpoint was not evaluated due to early study termination primarily because of limited efficacy. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
PFS: Subgroup of Participants With Met Diagnostic-Positive Squamous NSCLC [4] | ||||||||||||
End point description |
PFS is defined as the time between date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment with use of RECIST v1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (the appearance of one or more new lesions is also considered progression). PFS was to be estimated using Kaplan-Meier method.
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End point type |
Primary
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End point timeframe |
Baseline, every 6 weeks (±7 days) during the first 4 cycles (each cycle was 21 days) of treatment, then every 9 weeks (±7 days) during the maintenance treatment until disease progression or death (maximum up to approximately 32 months).
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| Notes [4] - 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: Endpoint was not evaluated due to early study termination primarily because of limited efficacy. |
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| Notes [5] - Endpoint was not evaluated due to early study termination primarily because of limited efficacy. [6] - Endpoint was not evaluated due to early study termination primarily because of limited efficacy. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Overall Survival (OS) | ||||||||||||
End point description |
OS is defined as the time from randomization until death due to any cause.
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End point type |
Secondary
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End point timeframe |
From baseline until death (maximum up to approximately 32 months).
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| Notes [7] - Endpoint was not evaluated due to early study termination primarily because of limited efficacy. [8] - Endpoint was not evaluated due to early study termination primarily because of limited efficacy. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With Objective Response | ||||||||||||
End point description |
Objective response (OR) is defined as a complete response (CR) or partial response (PR). OR is measured using RECIST v1.1. Participants without a post-baseline tumor assessment were considered as non-responders.
CR: Disappearance of all target and non-target lesions and normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm);
PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
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End point type |
Secondary
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End point timeframe |
Baseline, every 6 weeks (±7 days) during the first 4 cycles (each cycle was 21 days) of treatment, then every 9 weeks (±7 days) during the maintenance treatment until disease progression or death (maximum up to approximately 32 months).
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| Notes [9] - Endpoint was not evaluated due to early study termination primarily because of limited efficacy. [10] - Endpoint was not evaluated due to early study termination primarily because of limited efficacy. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Duration of Objective Response (DOR) | ||||||||||||
End point description |
OR is defined as a CR or PR. OR is measured using RECIST v1.1. DOR: time from the first occurrence of a documented OR to disease progression (as determined by the investigator using RECIST v1.1) or death from any cause during the study. Participants without a postbaseline tumor assessment were considered as nonresponders. OR was not evaluated due to discontinuation of the clinical development of onartuzumab. CR: Disappearance of all target and non-target lesions and normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
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End point type |
Secondary
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End point timeframe |
Baseline, every 6 weeks (±7 days) during the first 4 cycles (each cycle was 21 days) of treatment, then every 9 weeks (±7 days) during the maintenance treatment until disease progression or death (maximum up to approximately 32 months)
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| Notes [11] - Endpoint was not evaluated due to early study termination primarily because of limited efficacy. [12] - Endpoint was not evaluated due to early study termination primarily because of limited efficacy. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With Disease Control | ||||||||||||
End point description |
Disease control rate was defined as the rate of participants with CR, PR, or stable disease (SD) maintained for ≥6 weeks. CR: Disappearance of all target and non-target lesions and normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (the appearance of one or more new lesions is also considered progression).
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End point type |
Secondary
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End point timeframe |
Baseline, every 6 weeks (±7 days) during the first 4 cycles (each cycle was 21 days) of treatment, then every 9 weeks (±7 days) during the maintenance treatment until disease progression or death (maximum up to approximately 32 months).
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| Notes [13] - Endpoint was not evaluated due to early study termination primarily because of limited efficacy. [14] - Endpoint was not evaluated due to early study termination primarily because of limited efficacy. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Maximum Serum Concentration for Onartuzumab [15] | ||||||||
End point description |
Maximum serum concentration is expressed in micrograms per milliliter (mcg/mL). Safety population included all participants who were randomized and had received at least one dose of study drug.
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End point type |
Secondary
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End point timeframe |
Predose (within 1 hour), 30 minutes postdose on Day 1 of Cycle 4 (each cycle was 21 days)
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| Notes [15] - 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: The endpoint does not apply to the arm group 2 (Placebo arm). |
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| No statistical analyses for this end point | |||||||||
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End point title |
Minimum Serum Concentration for Onartuzumab [16] | ||||||||
End point description |
Minimum serum concentration is expressed in micrograms per milliliter (mcg/mL). Safety population
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End point type |
Secondary
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End point timeframe |
Predose (within 1 hour) on Day 1 of Cycle 4 (each cycle was 21 days)
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| Notes [16] - 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: The endpoint does not apply to the arm group 2 (Placebo arm). |
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum Serum Concentrations for Paclitaxel | ||||||||||||
End point description |
For paclitaxel PK, only samples from 1 participant from the onartuzumab treatment arm were collected and analyzed. As these data are very limited, no PK parameters were calculated for Paclitaxel.
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End point type |
Secondary
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End point timeframe |
Prior to first chemotherapy drug infusion (within 1 hour), 0-10 minutes, 2 hour (±30 minutes), 5, and 6 hour after end of paclitaxel infusion on Day 1 of induction Cycles 1 and 4 (each cycle was 21 days). Paclitaxel infusion was administered over 3 hours.
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| Notes [17] - Endpoint was not evaluated due to insufficient number of participants (<50%) with data. [18] - Endpoint was not evaluated due to insufficient number of participants (<50%) with data. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Area Under Curve From Time 0 to t (AUC[0-t]) For Platinum and Ultrafilterable Platinum | ||||||||||||
End point description |
AUC(0-t) was to be expressed in micrograms times (*) hour per milliliter (mcg*hour/mL). For platinum PK, only samples from 1 participant from the onartuzumab treatment arm were collected and analyzed. As these data are very limited, no PK parameters were calculated for platinum.
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End point type |
Secondary
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End point timeframe |
Prior to first chemotherapy drug infusion (within 1 hour), 0–5 minute, 1 hour (±15 minute), 3, and 6 hour after end of cisplatin (1-2 hours) or carboplatin (30-60 minutes) infusion on Day 1 of induction Cycles 1 and 4 (each cycle was 21 days)
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| Notes [19] - Endpoint was not evaluated due to insufficient number of participants (<50%) with data. [20] - Endpoint was not evaluated due to insufficient number of participants (<50%) with data. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
AUC(0-t) For Paclitaxel | ||||||||||||
End point description |
For paclitaxel PK, only samples from 1 participant from the onartuzumab treatment arm were collected and analyzed. As these data are very limited, no PK parameters were calculated for Paclitaxel.
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End point type |
Secondary
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End point timeframe |
Prior to first chemotherapy drug infusion (within 1 hour), 0-10 minutes, 2 hour (±30 minutes), 5, and 6 hour after end of paclitaxel infusion on Day 1 of induction Cycles 1 and 4 (each cycle was 21 days). Paclitaxel infusion was administered over 3 hours.
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| Notes [21] - Endpoint was not evaluated due to insufficient number of participants (<50%) with data. [22] - Endpoint was not evaluated due to insufficient number of participants (<50%) with data. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Maximum Serum Concentration for Platinum and Ultrafilterable Platinum | ||||||||||||
End point description |
For platinum PK, only samples from 1 participant from the onartuzumab treatment arm were collected and analyzed. As these data are very limited, no PK parameters were calculated for platinum.
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End point type |
Secondary
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End point timeframe |
Prior to first chemotherapy drug infusion (within 1 hour), 0–5 minute, 1 hour (±15 minute), 3, and 6 hour after end of cisplatin (12 hours) or carboplatin (3060 minutes) infusion on Day 1 of induction Cycles 1 and 4 (each cycle was 21 days)
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| Notes [23] - Endpoint was not evaluated due to insufficient number of participants (<50%) with data. [24] - Endpoint was not evaluated due to insufficient number of participants (<50%) with data. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants with anti-therapeutic antibody against onartuzumab | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Onartuzumab pre-dose (within 1 hour) on Day 1 of induction Cycles 1 and 4 (each cycle was 21 days), and on study drug discontinuation visit (maximum up to approximately 32 months)
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| Notes [25] - Endpoint was not evaluated due to insufficient number of participants (<50%) with data. [26] - Endpoint was not evaluated due to insufficient number of participants (<50%) with data. |
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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 |
Basline up to 32 months
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
Onartuzumab + Paclitaxel + Platinum Arm
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Reporting group description |
Onartuzumab was administered in the clinic on Day 1 of each 21-day cycle. The individual dose of onartuzumab for each participant was 15 mg/kg in 250 cc final 0.9% NSS. Paclitaxel was administered IV at a dose of 200 mg/m^2 over 3 hours after the completion of the onartuzumab infusion followed by platinum (cisplatin or carboplatin). Cisplatin IV infusion was administered 30 minutes after completion of the paclitaxel infusion at a dose of 75 mg/m^2 over 1 − 2 hours every 21 days up to 4 cycles or per standard of care at the institution or carboplatin (AUC 6 IV) every 21 days up to 4 cycles. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo + Paclitaxel + Platinum Arm
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Reporting group description |
Placebo was administered in the clinic on Day 1 of each 21-day cycle. The individual dose of placebo for each participant was 15 mg/kg in 250 cc final 0.9% NSS. Paclitaxel was administered IV at a dose of 200 mg/m^2 over 3 hours after the completion of the placebo infusion followed by platinum (cisplatin or carboplatin). Cisplatin IV infusion was administered 30 minutes after completion of the paclitaxel infusion at a dose of 75 mg/m^2 over 1 − 2 hours every 21 days up to 4 cycles or per standard of care at the institution or carboplatin (AUC 6 IV) every 21 days up to 4 cycles. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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15 Nov 2011 |
Protocol was amended for the following reasons:
The infusion time for onartuzumab/placebo and carboplatin was clarified. The correction for the Cockcroft-Gault method for calculation of creatinine clearance in females (for carboplatin dose calculation), was provided. For participants who consented to additional pharmacokinetic (PK) sampling, the timepoint for plasma paclitaxel PK at Cycle 1 Day 1 and Cycle 4 Day 1 was changed from 8 hours to 6 hours after the end of the paclitaxel infusion. |
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13 Apr 2012 |
Protocol has been amended for the following reasons:
The study exclusion criterion regarding participants with EGFR-activating mutations who are suitable for anti-EGFR therapy has been modified to allow for cases where treatment is unavailable to or refused by the patient.
It has been clarified that baseline weight (rather than screening weight) will be used to calculate onartuzumab/placebo dosage.
The timing of carboplatin treatment after paclitaxel infusion has been clarified.
The maximum allowed onartuzumab/placebo dose delay has been extended from 7 days to one treatment cycle.
Several chemotherapy dose modification tables have been modified for consistency with the accompanying text.
To more fully comply with updated regulations, serious adverse events (SAEs) and pregnancies should be reported within 24 hours rather than 1 working day; this change has been reflected throughout.
The number of patients and study sites has been corrected.
Baseline hematology and chemistry laboratory assessments will not have to be repeated at Cycle 1 Day 1 if the assessments were performed within 3 days before Cycle 1 Day 1.
During survival follow-up, the requirement for the reporting of non-serious adverse events has been removed; only SAEs considered related to study treatments need to be reported. |
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26 Jun 2013 |
Protocol was amended for the following reasons:
For the Sponsor’s internal decision-making process, a third data review by the Internal Monitoring Committee (IMC) has been added to assess the treatment effect in participants with Met diagnostic positive tumors at an earlier time point than the planned final analysis.
No crossover from placebo to onartuzumab treatment was allowed in this study. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
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. | |||
| Sponsor made a decision to discontinue further clinical development of onartuzumab due to the limited efficacy observed in the conduct of this study and was not based on safety-related issues. | |||
