An Efficacy and Safety Study of MORAb-003 in Platinum-Resistant or Refractory Relapsed Ovarian Cancer

Study Overview
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Brief Summary
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The study is being conducted to find out if paclitaxel works better when given together with an experimental drug called MORAb-003 (farletuzumab) or alone in patients with platinum-resistant or refractory relapsed ovarian cancer

Detailed Description
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Safety was assessed by the monitoring and recording of all adverse events (AEs), including drug hypersensitivity adverse events (DHAE), and serious adverse events (SAEs); clinical laboratory test (serum chemistry, hematology, urinalysis); tolerability (discontinuations, treatment delays, dose reductions); physical examinations (including vital signs assessment); 12-lead electrocardiograms (ECG) obtained in triplicate and reviewed by independent blinded cardiologist, and Karnofsky's performance status.

Official Title
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A Randomized, Double Blind, Placebo-Controlled Study of the Efficacy and Safety oF MORAb-003(Farletuzumab) in Combination With Paclitaxel Therapy in Subjects With Platinum-Resistant or Refractory Relapsed Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: MORAb-003 (farletuzumab)
* Drug: 0.9% Saline
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of non-mucinous epithelial ovarian cancer, including primary peritoneal and fallopian tube malignancies, measurable by CT or MRI scan assessed within 4 weeks prior to study entry Must have evidence of relapse by CA-125 (2xUpper Limit of Normal) or radiographically within 6 months of most recent platinum-containing chemotherapy. At least one of the lines of chemotherapy must have included a taxane. Must have been treated with debulking surgery and at least one line platinum-based chemotherapy; Subjects may have received up to four additional lines of chemotherapy after they developed platinum-resistance. Subjects must be candidate for repeat paclitaxel treatment Exclusion Criteria: Clinical contraindications to use of paclitaxel, which include: persistent Grade 2 or greater peripheral neuropathy prior hypersensitivity reaction that persisted despite rechallenge with or without desensitization or resulted in bronchospasm or hemodynamic instability or was at least Grade 2 and resulted in medication discontinuation Current diagnosis of epithelial ovarian tumor of low malignant potential (borderline carcinomas). Note: EOC with prior diagnosis of a low malignant potential tumor that has been surgically resected is acceptable provided the subject did Prior radiation therapy is excluded with the exception that it is allowable only if measurable disease for ovarian cancer is completely outside the radiation portal Known allergic reaction to a prior monoclonal antibody therapy or have any documented human anti-human antibody (HAHA). Previous treatment with MORAb-003 (farletuzumab).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>MORAb-003 (Farletuzumab) Plus Paclitaxel | Drug: MORAb-003 (farletuzumab)<br>* Farletuzumab (FAR) at 2.5 mg/kg was administered by intravenous (IV) infusion weekly on Day 1 of Weeks 1 to 12 (Cycle 1) and then in 4-week cycles with treatment administered on Day 1 of Weeks 1 to 3 for all subsequent cycles.<br>Drug: Paclitaxel<br> <br> * Other names: Paclitaxel (80 mg/m^2) was administered by IV infusion over 1 hour following administration of FAR.;|
| Placebo Comparator: 2<br>Placebo Plus Paclitaxel | Drug: 0.9% Saline<br>* Placebo (0.9% normal saline) was administered by IV infusion weekly on Day 1 of Weeks 1 to 12 (Cycle 1) and then in 4-week cycles with treatment administered on Day 1 of Weeks 1 to 3 for all subsequent cycles.<br>Drug: Paclitaxel<br> <br> * Other names: Paclitaxel (80 mg/m^2) was administered by IV infusion over 1 hour following administration of FAR.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS was defined as the time (in months) from the date of randomization to the date of the first observation of progression as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST), or death regardless of cause. If progression or death was not observed, 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). | Date of Randomization to date of disease progression or death (whichever came first), assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months | 
| Overall Survival (OS) | OS was defined as the time (in months) from the date of randomization to the date of death, whatever the 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. | Date of Randomization to date of death, assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response | BOR was defined as the percentage of participants having either a confirmed complete response (CR) or confirmed partial response (PR) using modified RECIST criteria by independent radiologist review. RECIST criteria was adjusted based on current medical practices and on possible differences between ovarian cancer and other solid tumors. Tumor assessments performed up to the initiation of further antitumor treatment were considered. Target lesions selected for response assessment were measured using computed tomography (CT) or magnetic resonance imaging (MRI) scans then graded according to the modified RECIST criteria, adjusted based on current medical practices and on possible differences between ovarian cancer and other solid tumors. Participants were assigned to one of the categories of change in disease state; CR, PR, progressive disease (PD), stable disease ( S)D, or not evaluable (NE). | Date of first study drug to disease progression/recurrence, assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months | 
| Time to Tumor Response (TTR) | TTR was derived for those participants with objective evidence of CR or PR, and was defined as the time (in months) from the date of randomization to the first documentation of object tumor response (TR). Analysis was based on the Kaplan-Meier estimated percentage of responders. This statistical analysis method measures the effect of study drug on tumor response over a period of time. | Date of Randomization to the first documentation of objective TR, assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian cancer, relapsed ovarian cancer, refractory ovarian cancer