Clinical Trial Results:
An Open Label Extension Study of the Efficacy of MORAb-003 in Subjects with Platinum-Sensitive Epithelial Ovarian Cancer in First Relapse
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Summary
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EudraCT number |
2009-015825-36 |
Trial protocol |
DE |
Global end of trial date |
05 Mar 2013
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Results information
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Results version number |
v2 |
This version publication date |
28 May 2016
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First version publication date |
15 Aug 2015
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Other versions |
v1 , v3 , v4 |
Version creation reason |
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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 |
MORAb-003-002A
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01018563 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Morphotek (subsidiary of Eisai)
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Sponsor organisation address |
210 Welsh Pool Road, Exton, United States, 19341
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Public contact |
Eisai Call Center, Eisai Inc., 888 422-4743,
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Scientific contact |
Eisai Call Center, Eisai Inc, 888 422-4743,
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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 |
05 Mar 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 |
05 Mar 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 |
To provide MORAb-003 to subjects who are enrolled in the protocol MORAb-003-002 and appear to be deriving benefit
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Protection of trial subjects |
This study was conducted in accordance with standard operating procedures (SOPs) of the Sponsor (or designee), which are designed to ensure adherence to Good Clinical Practice (GCP) guidelines as required by the following:
• Principles of the World Medical Association Declaration of Helsinki (World Medical Association, 2008)
• ICH E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, International Conference on Harmonisation of Pharmaceuticals for Human Use (2002)
• Title 21 of the United States (US) Code of Federal Regulations (US 21 CFR) regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and Institutional Review Board (IRB) regulations and applicable sections of US 21 CFR Part 312 (2013)
• European Clinical Trial Directive 2005/28/EC and European Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country. All suspected unexpected serious adverse reactions (SUSARs) were reported, as required, to the Competent Authorities of all involved EU member states.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Jan 2010
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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 |
United States: 2
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Country: Number of subjects enrolled |
Germany: 1
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Worldwide total number of subjects |
3
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EEA total number of subjects |
1
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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) |
2
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects must have participated in the MORAb-003-002 parent study, achieved normalization of cancer antigen 125 levels and/or tumor assessment of complete response, partial response, (or stable disease and an investigator’s assessment of a clinical benefit) after receiving farletuzumab in combination with standard chemotherapy to enter this study. | ||||||||||
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Pre-assignment
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Screening details |
- | ||||||||||
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Pre-assignment period milestones
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Number of subjects started |
3 | ||||||||||
Intermediate milestone: Number of subjects |
Eligible from MORAB-003-002: 3
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Number of subjects completed |
3 | ||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Farletuzumab | ||||||||||
Arm description |
Farletuzumab was initially administered by intravenous (IV) infusion once weekly at the same dose subjects were receiving in the MORAb-003-002 (NCT00318370) parent study (ie, 62.5 or 100 mg/m2). Dosage was changed per protocol amendment 12 May 2011 to 3 times the initial dosage (ie, 187.5 or 300 mg/m2) administered every 3 weeks (Q3W). | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Farletuzumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Farletuzumab was initially administered by IV infusion once weekly at the same dose subjects were receiving in the MORAb-003-002 parent study (ie, 62.5 or 100 mg/m2); dosage was changed per protocol amendment 12 May 2011 to 3 times the initial dosage (ie, 187.5 or 300 mg/m2) administered Q3W. Farletuzumab was continued as a single-agent maintenance therapy until relapse. If the second relapse was platinum-sensitive (platinum-free interval >6 months), the subject could receive carboplatin and taxane chemotherapy in combination with farletuzumab for an additional 6 cycles followed by single-agent farletuzumab maintenance therapy.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Farletuzumab
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Reporting group description |
Farletuzumab was initially administered by intravenous (IV) infusion once weekly at the same dose subjects were receiving in the MORAb-003-002 (NCT00318370) parent study (ie, 62.5 or 100 mg/m2). Dosage was changed per protocol amendment 12 May 2011 to 3 times the initial dosage (ie, 187.5 or 300 mg/m2) administered every 3 weeks (Q3W). | ||
Subject analysis set title |
Farletuzumab (per GCIG criteria)
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Maintenance infusions of farletuzumab in subjects with platinum-sensitive epithelial ovarian cancer in first relapse
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Subject analysis set title |
Farletuzumab (CA125 criteria)
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Maintenance infusions of farletuzumab in subjects with platinum-sensitive epithelial ovarian cancer in first relapse
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Subject analysis set title |
Farletuzumab (per RECIST)
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Maintenance infusions of farletuzumab in subjects with platinum-sensitive epithelial ovarian cancer in first relapse
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Subject analysis set title |
Farletuzumab (62.5 mg/m2)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Analysis set used for displaying duration of CA125 Response.
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Subject analysis set title |
Farletuzumab (100 mg/m2)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Analysis set used for displaying duration of CA125 Response.
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End point title |
Duration of ovarian tumor marker (CA125) response [1] | ||||||||||||||||||||||||||||
End point description |
The Duration of CA125 response, defined as the time from the date of the initial CA125 response (ie, prior to enrollment in the parent study) to the first documentation of progressive disease (PD) by either Gynecologic Cancer Inter Group (GCIG) criteria for CA125 level or Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 or by the date of death due to any cause, whichever occurred first. Disease progression as assessed by the investigator per RECIST v1.0 was defined as at least a 20% increase in sum of longest diameters (RECIST definition) compared to baseline (or lowest sum while on study if less than baseline), or any new lesions (measurable or nonmeasurable). Disease progression per CA125 was defined as the first of 2 consecutive CA125 values greater than twice the upper limit of normal. C= data censored at earlier non-PD assessment if PD did not occur.
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End point type |
Primary
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End point timeframe |
From Baseline (Day 1) up to study completion i.e. approximately 3.2 years
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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: No comparative analysis conducted. The study objective was to provide MORAb-003 to subjects who are enrolled in the protocol MORAb-003-002 and appear to be deriving benefit. A confidence interval cannot be calculated in this situation because the Dose Group 100 contains only 1 subject; no variability estimate can be derived and the pooled standard error of the treatment difference cannot be calculated. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Progression free survival (PFS) by Criteria Type | ||||||||||||||||||||||||||||
End point description |
PFS was defined as the time from the date of first dose of study medication during the parent study to the date of disease progression (either by GCIG for CA125 criteria or RECIST v.1.0, whichever ocured first) or by the date of death due to any cause. Disease progression as assessed by the investigator per RECIST v1.0 was defined as at least a 20% increase in sum of longest diameters (RECIST definition) compared to baseline (or lowest sum while on study if less than baseline), or any new lesions (measurable or nonmeasurable). Disease progression per CA125 was defined as the first of 2 consecutive CA125 values greater than twice the upper limit of normal. C= data censored at earlier non-PD assessment if PD did not occur.
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End point type |
Secondary
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End point timeframe |
From Baseline (Day 1) up to study completion i.e. approximately 3.2 years
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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 was defined from the date of first dose of study medication during the parent study to date of death due to any cause. Participants who were alive had their OS time censored at the date they were last known to be alive. C= censored data.
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End point type |
Secondary
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End point timeframe |
From Baseline (Day 1) until date of death from any cause or up to study completion i.e. approximately 3.2 years
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Duration of Second Remission | ||||||||||||||
End point description |
The prolongation of second and subsequent responses to chemotherapy plus farletuzumab relative to initial remission was assessed. Length of 1st remission in parent study was determined prior to entry in parent study. The 'length of 2nd remission (1st remission in this study)' was defined as the duration from the start of carboplatin/taxane therapy in parent study to the start date of carboplatin/taxane in this study. The length of 2nd remission is censored at date of study discontinuation if participant did not receive any carboplatin/taxane therapy during this study. C = censored data.
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End point type |
Secondary
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End point timeframe |
From Baseline (Day 1) until date of death from any cause or up to study completion i.e. approximately 3.2 years
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Duration of Third Remission | ||||||||||||
End point description |
The 'length of 3rd remission (2nd remission in this study)' is defined as the duration from the start of carboplatin/taxane therapy in this study to the start date of subsequent carboplatin/taxane in this study. The length of 3rd remission is censored at date of study discontinuation if participant did not receive subsequent carboplatin/taxane therapy during this study. C = censored data.
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End point type |
Secondary
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End point timeframe |
From Baseline (Day 1) until date of death from any cause or up to study completion i.e. approximately 3.2 years
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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 |
For each participant, from the first dose till 30 days after the last dose or up to study completion i.e. approximately 3.2 years
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Adverse event reporting additional description |
Treatment emergent adverse events (TEAEs), defined as an AE that started/increased in severity on/after the first dose of study drug up to 30 days after final dose of study drug. Per the study Statistical Analysis Plan (SAS), the TEAEs presented include serious and non-serious TEAEs.
Additionally, serious TEAEs are presented separately.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.1
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Reporting groups
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Reporting group title |
Farletuzumab
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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12 May 2011 |
Part A.
- Based on results of population pharmacokinetic (PK) studies, farletuzumab dosage was changed to Q3W intervals, using 3 times the weekly dose previously given. Due to this change, visits were changed to every 3 weeks, and all references to cycles were deleted. With the increased dose level, there was no need to dilute farletuzumab with normal saline. Instructions for preparation and administration of farletuzumab were updated accordingly
- Farletuzumab was added to the product name to reflect the United States Adopted Names designation for MORAb-003
- Collection of serum samples for farletuzumab concentration was changed to every other visit (every 6 weeks) pre- and postinfusion in order to obtain additional information on serum levels maintained in this population. In addition, pre- and postinfusion serum samples were to be collected during the final 2 weekly visits prior to switching to the Q3W schedule
- Collection of Human Anti-Human Antibody (HAHA) Results samples was changed to pre-infusion every other visit (every 6 weeks)
- Due to the long-term follow-up in this population, the interval between Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 (Therasse et al., 2000) evaluations was increased to every 6 visits (every 18 weeks) as long as subjects remained clinically stable and the CA125 remained within normal limits. For any subjects receiving chemotherapy, the RECIST evaluations were changed to every 9 weeks (every 3 visits). Also, all RECIST evaluations were to be based on local radiology readings. All references to a central reader were deleted |
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12 May 2011 |
Part B.
- A secondary objective was added to assess farletuzumab levels during Q3W dosing compared to drug levels during weekly dosing
- The expected number of subjects was revised from 4 to 3. One of the expected subjects experienced a relapse and discontinued from the main study prior to initiation of the extension
- Antibody-dependent cell cytotoxicity testing was removed from the protocol due to sample stability issues
- Criteria for removal and replacement of study subjects were updated to include:
> An AE deemed to be intolerable, including a farletuzumab-related allergic reaction
> A subject being lost to follow-up
> A subject experiencing progressive disease by RECIST or CA125 criteria that is determined to be platinum-resistant/-refractory
> A subject’s death |
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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. | |||
| Study was terminated by the sponsor following the futile results of the analysis of a phase 3 study in a similar patient population. | |||
