Effectiveness of MORAb-003 in Women With Ovarian Cancer Who Have Relapsed After Platinum-Based Chemotherapy

Study Overview
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Brief Summary
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The purpose of this study is to determine if an investigational drug called MORAb-003 is useful by itself or when used with other approved cancer drugs in treating women with ovarian cancer. MORAb-003 is a monoclonal antibody directed against an antigen on most ovarian cancers.

Detailed Description
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MORAb-003 is a monoclonal antibody that has the potential to be an effective agent against epithelial ovarian cancer (including primary fallopian tube and peritoneal adenocarcinoma) either alone or in combination with other drugs. MORAb-003 works by a different mechanism from other cancer therapeutics and has been shown to be well tolerated. This study allows the opportunity to determine if MORAb-003 can work either as a single agent to treat a CA125-only relapse, or in combination with standard platinum and taxane chemotherapy to treat a symptomatic relapse, and to prolong a second response to chemotherapy.

Official Title
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A Study of the Efficacy of MORAb-003 in Subjects With Platinum-Sensitive Epithelial Ovarian Cancer in First Relapse

Conditions
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Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Neoplasms

Intervention / Treatment
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* Drug: Farletuzumab
* Drug: Chemo Plus Far


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects at least 18 years of age, with a histologically confirmed diagnosis of non-mucinous epithelial ovarian cancer (including fallopian tube and primary peritoneal cancer) in first relapse after a first remission of 6 to 18 months duration. Subjects must have undergone surgery. Subjects must have received primary chemotherapy, including at least one platinum agent. Subject is eligible for retreatment with the same chemotherapy regimen that was used to induce remission (Exception: may reduce the dose of or discontinue taxane if contraindicated due to neurotoxicity.) CA125 must have been elevated prior to original chemotherapy. CA125 must be elevated at the time of relapse. Life expectancy greater than or equal to 6 months, as estimated by the investigator. Eastern Cooperative Oncology Group performance status of 0, 1 or 2 Subjects must consent to use a medically acceptable method of contraception throughout the study period and for 28 days after final MORAb-003 administration, unless surgically sterile. Any significant concomitant medical conditions must be well controlled and stable in the opinion of the investigator for at least 30 days prior to Study Day 1. Laboratory and clinical results within the 2 weeks prior to Study Day 1 as follows: Absolute neutrophil count (ANC) ≥ 1.2 x 10e9/L Platelet count ≥ 100 x 10e9/L Hemoglobin ≥ 8 g/dL Subject must be willing and able to provide written informed consent. Translations of informed consent information may be provided, subject to the local institutional review board's (IRB's) policy. Exclusion Criteria: Known central nervous system (CNS) tumor involvement. Evidence of other active malignancy requiring treatment. Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class III or IV, angina not well controlled by medication, or myocardial infarction within 6 months). Electrocardiogram (ECG) demonstrating clinically significant arrhythmias (Exception: Subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia [SVT], are eligible). Active serious systemic disease, including active bacterial or fungal infection. Active hepatitis or HIV infection. Treatment within three months with immunomodulatory therapy (e.g. interferons, immunoglobulin therapy, interleukin 1 receptor antagonist [IL-1RA] or systemic corticosteroids). Short term systemic corticosteroids or topical or intra-articular steroids are acceptable, subject to the judgment of the investigator. Treatment with a monoclonal antibody therapy AND have evidence of an immune or allergic reaction or documented HAHA. Maintenance of first remission by taxane or other chemotherapeutic agent(s). Initiation or planned initiation of cancer therapy not given to induce primary remission. Substitutions of agents materially similar to those used in the original regimen are permissible. Breast-feeding, pregnant, or likely to become pregnant during the study.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Far Only<br>Farletuzumab only (Far Only): farletuzumab, 100 milligrams (mg)/square meter (m2). | Drug: Farletuzumab<br>* Weekly Farletuzumab infusions Dose dependent on dosing group<br>* Other names: Far Only;|
| Experimental: Chemo Plus Far<br>Chemo+Far: paclitaxel 175 mg/m2 (or docetaxel, 75 mg/m2) plus carboplatin area under the concentration-time curve (AUC) 5-6 intravenously (IV) on Day 1 of a 21-day cycle plus farletuzumab, 100 mg/m2. | Drug: Chemo Plus Far<br>* Chemo+Far: paclitaxel 175 mg/m2 (or docetaxel, 75 mg/m2) plus carboplatin area under the concentration-time curve (AUC) 5-6 intravenously (IV) on Day 1 of a 21-day cycle plus farletuzumab, 100 mg/m2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serologic Response (Change in CA125 Level) | Defined using modified Gynecologic Cancer Intergroup (GCIG) criteria: Number of participants who achieved a 50% response = >50% decrease from baseline CA-125 (higher of 2 pretreatment CA-125 assessments and the level must be at least 52.5 kU/L). | Baseline to response (up to 30 weeks) | 
| Serologic Response (Change in Cancer Antigen [CA-125] Level) | Defined using modified Gynecologic Cancer Intergroup (GCIG) criteria: Number of participants who had a 50% response = >50% decrease from baseline CA-125 (higher of 2 pretreatment CA-125 assessments and the level must be at least 52.5 kU/L). | Baseline to response (up to 27 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Serologic Response (Change in CA-125 Level) | Time to Serologic Response is defined as the time (weeks) from the date of first farletuzumab infusion to first documentation of 50% decrease from baseline CA-125 (higher of 2 pretreatment CA-125 assessments and at least twice the upper limit of normal) and then confirmed after 21 days. | Baseline to response (up to 27 weeks) | 
| Duration of Serologic Response (CA-125) | Calculated as the time from the first documentation of 50% or greater reduction in CA-125 to the first documentation of serologic progression or death due to any cause. Serologic progression was defined as the first date of the CA-125 level being >2 X ULN on two occasions. | Baseline to response (up to 44 months) | 
| Overall Response Rate | The Overall Response Rate (ORR) will be determined by applying standard RECIST criteria to objective measures of disease, such as CT or MRI scans. Participants will be assigned to one of the categories of change in disease status, namely, complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). ORR is defined as the percentage of participants with objective evidence of CR or PR. | Baseline to response (up to 44 months) | 
| Progression-free Survival (PFS) | PFS is defined for participants treated in Chemo Plus Far as the time (in months) from date of first dose in Chemo Plus Far until date of the first observation of progression based on first date of the CA-125 >2 X ULN on two occasions, or date of death, whatever the cause. If progression or death is not observed for a participant, the PFS time is censored at the later date of last tumor assessment or CA125 assessment without evidence of progression prior to the date of initiation of further anti-tumor treatment. | Baseline to response (up to 44 months) | 
| Percentage of Participants Who Had a Prolongation of Remission | Percentage of participants whose second remission was longer than their first remission. The length of remission will be determined for participants who attain CR or PR (or SD and investigator's assessment of clinical benefit). Prolongation of remission will be defined as a length of remission occurring on this study that is ≥ 1 day longer than the length of remission to the original therapy. The length of remission on this study (second remission) will be defined as the amount of time from the date of first CR or PR to the end of this remission. | Baseline to response (up to 44 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian Cancer, Primary Fallopian Tube Cancer, Peritoneal Cancer