Efficacy and Safety of Farletuzumab (MORAb-003) in Combination With Carboplatin and Taxane in Participants With Platinum-sensitive Ovarian Cancer in First Relapse

Phase 3

Terminated

Conditions: Ovarian Cancer

Interventions: Drug: Farletuzumab
Drug: Carboplatin
Drug: Farletuzumab-matched placebo
Drug: Taxane

Registration Number: NCT00849667

Lead Sponsor: Morphotek

Brief Summary: This research is being done to find out if Carboplatin and Taxane works better alone or when given with an experimental drug called MORAb-003(farletuzumab) in subjects with first platinum sensitive relapsed ovarian cancer.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 1100

Inclusion Criteria

A histologically or cytologically confirmed diagnosis of non-mucinous epithelial ovarian cancer including primary peritoneal or fallopian tube malignancies
Must have measurable disease by CT or MRI scan
Must have relapsed radiologically with a randomization date within ≥6 and < 24 months of completion of first-line platinum chemotherapy
Have been treated with debulking surgery and first-line platinum and taxane based chemotherapy.
Prior bevacizumbab maintenance is allowed. The last dose of bevacizumab must have been at least 30 days before study Day 1. No cytotoxic maintenance therapy (e.g. taxane) or cancer vaccine therapy is allowed.
Must be a candidate for carboplatin and taxane therapy
Neurologic function: neuropathy (sensory and motor) ≤CTCAE Grade 1

Exclusion Criteria

Subjects who never responded to first-line platinum-based therapy or whose first relapse occurs <6 months or >24 months from the last platinum therapy
Subjects who have received other therapy to treat their ovarian cancer since relapse
Known central nervous system (CNS) tumor involvement
Evidence of other active invasive malignancy requiring treatment in the past 5 years
Known allergic reaction to a prior monoclonal antibody therapy or have any documented HAHA
Previous treatment with MORAb-003 (farletuzumab)
Clinical contraindications to use of a taxane

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Farletuzumab-matched placebo	Participants will receive farletuzumab-matched placebo (0.9 percent \[%\] saline) administer as an IV infusion weekly, followed by taxane (paclitaxel \[175 mg/m\^2\] or docetaxel \[75 mg/m\^2\]), administer as IV infusion and followed by carboplatin (to maintain AUC 5-6 mg/mL/minute), administer as IV infusion, every three weeks on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab-matched placebo (0.9% saline), administer as IV infusion, weekly is given until disease progression.
Farletuzumab (1.25 mg/kg)	Taxane	Participants will receive farletuzumab 1.25 milligram per kilogram (mg/kg) administer as an intravenous (IV) infusion weekly, followed by taxane (paclitaxel \[175 milligram per meter square {mg/m\^2}\] or docetaxel \[75 mg/m\^2\]), administer as IV infusion and followed by carboplatin (to maintain area under curve \[AUC\] 5-6 milligram per milliliter per minute \[mg/mL/minute\]), administer as IV infusion, every three weeks, on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab 1.25 mg/kg, administer as IV infusion, weekly is given until disease progression.
Placebo	Taxane	Participants will receive farletuzumab-matched placebo (0.9 percent \[%\] saline) administer as an IV infusion weekly, followed by taxane (paclitaxel \[175 mg/m\^2\] or docetaxel \[75 mg/m\^2\]), administer as IV infusion and followed by carboplatin (to maintain AUC 5-6 mg/mL/minute), administer as IV infusion, every three weeks on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab-matched placebo (0.9% saline), administer as IV infusion, weekly is given until disease progression.
Farletuzumab (2.5 mg/kg)	Taxane	Participants will receive farletuzumab 2.5 mg/kg administer as an IV infusion weekly, followed by taxane (paclitaxel \[175 mg/m\^2\] or docetaxel \[75 mg/m\^2\]), administer as IV infusion and followed by carboplatin (to maintain AUC 5-6 mg/mL/minute), administer as IV infusion, every three weeks on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab 2.5 mg/kg, administer as IV infusion, weekly is given until disease progression.
Farletuzumab (1.25 mg/kg)	Carboplatin	Participants will receive farletuzumab 1.25 milligram per kilogram (mg/kg) administer as an intravenous (IV) infusion weekly, followed by taxane (paclitaxel \[175 milligram per meter square {mg/m\^2}\] or docetaxel \[75 mg/m\^2\]), administer as IV infusion and followed by carboplatin (to maintain area under curve \[AUC\] 5-6 milligram per milliliter per minute \[mg/mL/minute\]), administer as IV infusion, every three weeks, on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab 1.25 mg/kg, administer as IV infusion, weekly is given until disease progression.
Farletuzumab (2.5 mg/kg)	Carboplatin	Participants will receive farletuzumab 2.5 mg/kg administer as an IV infusion weekly, followed by taxane (paclitaxel \[175 mg/m\^2\] or docetaxel \[75 mg/m\^2\]), administer as IV infusion and followed by carboplatin (to maintain AUC 5-6 mg/mL/minute), administer as IV infusion, every three weeks on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab 2.5 mg/kg, administer as IV infusion, weekly is given until disease progression.
Placebo	Carboplatin	Participants will receive farletuzumab-matched placebo (0.9 percent \[%\] saline) administer as an IV infusion weekly, followed by taxane (paclitaxel \[175 mg/m\^2\] or docetaxel \[75 mg/m\^2\]), administer as IV infusion and followed by carboplatin (to maintain AUC 5-6 mg/mL/minute), administer as IV infusion, every three weeks on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab-matched placebo (0.9% saline), administer as IV infusion, weekly is given until disease progression.
Farletuzumab (2.5 mg/kg)	Farletuzumab	Participants will receive farletuzumab 2.5 mg/kg administer as an IV infusion weekly, followed by taxane (paclitaxel \[175 mg/m\^2\] or docetaxel \[75 mg/m\^2\]), administer as IV infusion and followed by carboplatin (to maintain AUC 5-6 mg/mL/minute), administer as IV infusion, every three weeks on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab 2.5 mg/kg, administer as IV infusion, weekly is given until disease progression.
Farletuzumab (1.25 mg/kg)	Farletuzumab	Participants will receive farletuzumab 1.25 milligram per kilogram (mg/kg) administer as an intravenous (IV) infusion weekly, followed by taxane (paclitaxel \[175 milligram per meter square {mg/m\^2}\] or docetaxel \[75 mg/m\^2\]), administer as IV infusion and followed by carboplatin (to maintain area under curve \[AUC\] 5-6 milligram per milliliter per minute \[mg/mL/minute\]), administer as IV infusion, every three weeks, on Day 1 of each 21-day cycle for 6 cycles (combination therapy). Following completion of combination therapy, maintenance treatment with farletuzumab 1.25 mg/kg, administer as IV infusion, weekly is given until disease progression.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)	PFS was defined as the time (in months) from the date of randomization to the date of the first observation of progression based on the independent radiologic assessment (modified response evaluation criteria in solid tumors \[RECIST\]), or date of death, whatever the cause. As per RECIST, disease progression was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. If progression or death was not observed for a participant, the PFS time was censored at the date of the last tumor assessment without evidence of progression before the date of initiation of further antitumor treatment, or the cutoff date (whichever was earlier).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Length of Second Remission Greater Than First Remission	From the date of last dose of platinum-based chemotherapy to date of relapse and date of last dose of platinum-based chemotherapy to first observation of progression (up to 48 months)	Length of first remission was defined as a.) the period of time (in months) from the date of completion of previous platinum-based chemotherapy until date of first relapse (that is, first observation of progression). It was assumed that the date of first relapse was the earlier of progression by CA-125 or progression by radiologic assessment, as judged by the investigator using GCIG criteria. b.) the period of time (in months) from the date of completion of previous platinum-based chemotherapy (used prior to study entry) until date of randomization. The length of the second remission was defined as the period of time (in months) from the date of completion of platinum-based chemotherapy until the first observation of progression based on GCIG criteria. Based on GCIG criteria, disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.
Duration of Tumor Response	From the first date of confirmed objective response (CR or PR) to first date of progression or death due to any cause (up to 48 months)	Duration of response was defined as the time (in months) from first documentation of objective response (confirmed CR or PR) to the first documentation of objective tumor progression or death due to any cause. Duration of response was derived only for those participants with objective evidence of confirmed CR or PR.
Overall Survival (OS)	From the date of randomization until date of death from any cause, or study termination by sponsor, whichever came first (up to 48 months)	OS was defined as the time (in months) from the date of randomization to the date of death, due to any cause. If death was not observed for a participant, the survival time was censored on the last date the participant was known to be alive or the cutoff date, whichever was earlier.
Cancer Antigen-125 (CA-125) Progression-Free Survival	From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)	CA-125 PFS was defined as the time (in months) from the date of randomization until the date of the first observation of progression based on the Rustin criteria, or date of death, whatever the cause. If progression or death was not observed for a participant, the CA-125 PFS time was censored at the date of the last CA-125 assessment without evidence of progression before the date of initiation of further antitumor treatment or the "primary analysis cut off" date, whichever was earlier. Based on Rustin criteria, progressive disease (PD) was a rise in CA125 since beginning of consolidation or previously normal CA125 that rises to greater than or equal to (\>=) 2 multiple (\) ULN with either event documented on two occasions or CA-125 \>=2\nadir value with either event documented on two occasions.
Progression-Free Survival Based on Gynecologic Cancer InterGroup (GCIG) Criteria	From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)	PFS using GCIG criteria was defined as time (in months) from date of randomization until date of first observation of progression based on GCIG criteria, or date of death, whatever the cause. If progression or death was not observed for a participant, GCIG PFS time was censored at later date of last tumor assessment or CA-125 assessment without evidence of progression before date of initiation of further antitumor treatment or the "primary analysis cut off" date, whichever was earlier. Disease progression per GCIG: Participants with elevated CA-125 pretreatment and normalisation of CA-125 must show evidence of CA-125 \>=two times ULN on two occasions at least one week apart or participants with elevated CA-125 pretreatment, which never normalises must show evidence of CA-125 \>=two times nadir value on two occasions at least one week apart or participants with CA-125 in normal range pretreatment must show evidence of CA-125 \>=two times ULN on two occasions at least one week apart.
Time to Tumor Response (TTR)	From the date of randomization to first documentation of objective response (up to 48 months)	Time to tumor response was defined as the time (in months) from the date of randomization to first documentation of objective tumor response. Time to tumor response was derived for those participants with objective evidence of CR or PR.
Percentage of Participants With Serologic Response (SR)	Up to 48 months	SR was defined as either normalization, 75% response, or 50% response using the Rustin criteria. Percentage of participants with 50% SR, 75% SR and SR leading to normalization were reported. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of four CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level). A 75% response was established if there had a serial decrease in serum CA-125 levels of 75% over three samples. In both the 50% and 75% response definitions, the final sample was analyzed at least 28 days after the previous sample.
Time to 50% Serologic Response (TSR)	From the date of randomization to first documentation of 50% SR (up to 48 months)	TSR was defined as the time (in months) from the date of randomization to first documentation of 50% SR. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of three CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level).
Vd: Volume of Distribution of Total Carboplatin and Total Paclitaxel	Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)
Mean Functional Assessment of Cancer Therapy-Ovarian Treatment Outcome Index (FACT-O TOI) Scores	Cycle 3, Cycle 6, Cycle 12 (each cycle length=21 days)	Participant-reported Quality of Life (QoL) was measured using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O), version 4 and reported in the Treatment Outcome Index (TOI) format. TOI is a 26-item subset of the FACT-O questionnaire composed of the raw sum of the physical well-being subscale (7 items), the functional well-being subscale (7 items), and the ovarian cancer subscale (12 items). Each item was scored on a scale of 0 (not at all) to 4 (very much). Some items were reversed scored. Scores from each subsection were summed into one composite score, termed the FACT-O TOI score which ranged from 0 to 104 and a higher score reflected better QoL. As per planned analysis, farletuzumab treatment groups 1.25 mg/kg and 2.5 mg/kg were pooled for the QoL assessment.
Percentage of Participants With Objective Response	From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 48 months)	Objective response was defined as either a confirmed complete response (CR) or confirmed partial response (PR) as assessed by investigator based on response evaluation criteria in solid tumors version 1.1 (RECIST version 1.1). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.
Duration of 50% Serologic Response	From the first date of documentation of response to first documentation of serologic progression or death due to any cause (up to 48 months)	Duration of SR was defined as the time (in months) from first documentation of response to the first documentation of 50% serologic progression or death due to any cause. For responding participants who did not have serologic progression or did not die and who 1) were either still on study at the time of an analysis, 2) were given antitumor treatment other than study treatment, or 3) were withdrawn from study follow-up before documentation of serologic progression, the duration of SR was censored at the last date the participant was known to be without serologic progression. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of three CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level).
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Total Carboplatin and Total Paclitaxel	Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)
AUC (0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Total Carboplatin and Total Paclitaxel	Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)
Percentage of Participants With Clinical Benefit	Up to 48 months	Clinical benefit was defined as a confirmed CR or a confirmed PR, or stable disease (SD) using RECIST 1.0 criteria. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non target lesions.
Cmax: Maximum Observed Plasma Concentration of Total Carboplatin and Total Paclitaxel	Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)
T1/2: Terminal Half-life of Total Carboplatin and Total Paclitaxel	Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)
CL: Clearance of Total Carboplatin and Total Paclitaxel	Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)

Trial Locations

Locations (342): University Of Alabama At Birmingham
🇺🇸
Birmingham, Alabama, United States
Oncology Specialties, PC
🇺🇸
Huntsville, Alabama, United States
Arizona Hematology & Oncology Associates
🇺🇸
Phoenix, Arizona, United States
St. Joseph's Hospital, Barrow Neurology Clinics
🇺🇸
Phoenix, Arizona, United States
Arizona Oncology Associates
🇺🇸
Tucson, Arizona, United States
Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
Providence St. Joseph Medical Center
🇺🇸
Burbank, California, United States
California Cancer Care, Inc.
🇺🇸
Greenbrae, California, United States
University of California San Diego
🇺🇸
La Jolla, California, United States
University of California Los Angeles Medical Center
🇺🇸
Los Angeles, California, United States
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University Of Alabama At Birmingham
🇺🇸Birmingham, Alabama, United States