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

Phase 2

Completed

Conditions: Ovarian Cancer
Peritoneal Neoplasms
Fallopian Tube Cancer

Interventions: Drug: Chemo Plus Far
Drug: Farletuzumab

Registration Number: NCT00318370

Lead Sponsor: Morphotek

Brief Summary: 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: 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

1. to treat a CA125-only relapse, or

2. in combination with standard platinum and taxane chemotherapy to treat a symptomatic relapse, and

3. to prolong a second response to chemotherapy.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 58

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemo Plus Far	Chemo Plus Far	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.
Far Only	Farletuzumab	Farletuzumab only (Far Only): farletuzumab, 100 milligrams (mg)/square meter (m2).

Primary Outcome Measures

Name	Time	Method
Serologic Response (Change in CA125 Level)	Baseline to response (up to 30 weeks)	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).
Serologic Response (Change in Cancer Antigen [CA-125] Level)	Baseline to response (up to 27 weeks)	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).

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate	Baseline to response (up to 44 months)	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.
Progression-free Survival (PFS)	Baseline to response (up to 44 months)	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.
Time to Serologic Response (Change in CA-125 Level)	Baseline to response (up to 27 weeks)	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.
Percentage of Participants Who Had a Prolongation of Remission	Baseline to response (up to 44 months)	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.
Duration of Serologic Response (CA-125)	Baseline to response (up to 44 months)	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.

Trial Locations

Locations (19): The Cancer Institute of New Jersey
🇺🇸
New Brunswick, New Jersey, United States
Hematology and Oncology Specialists, LLC
🇺🇸
Metarie, Louisiana, United States
The Center for Cancer and Hematologic Disease
🇺🇸
Cherry Hill, New Jersey, United States
Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
Cooper University Hospital
🇺🇸
Voorhees, New Jersey, United States
Gynecology Oncology Research & Development
🇺🇸
Greenville, South Carolina, United States
Nationales Centrum fur Tumorerkrankungen
🇩🇪
Heidelberg, Germany
Gabrail Cancer Center
🇺🇸
Canton, Ohio, United States
St. Vincent Gynecologic Oncology
🇺🇸
Indianapolis, Indiana, United States
Peninsula Cancer Center
🇺🇸
Newport News, Virginia, United States
Tyler Cancer Center
🇺🇸
Tyler, Texas, United States
Mary Crowley Medical Research Center
🇺🇸
Dallas, Texas, United States
Krankenhaus Nordwest
🇩🇪
Frankfurt, Germany
Jayne Gurtler, M.D.
🇺🇸
Metairie, Louisiana, United States
New York Oncology Hematology
🇺🇸
Albany, New York, United States
Lehigh Valley Women's Cancer Center
🇺🇸
Allentown, Pennsylvania, United States
South Texas Oncology & Hematology
🇺🇸
San Antonio, Texas, United States
Northern Virginia Pelvic Surgery Associates
🇺🇸
Annandale, Virginia, United States
Sharp HealthCare
🇺🇸
San Diego, California, United States