A Study to Assess the Efficacy and Safety of Farletuzumab (MORAb 003) in Combination With Carboplatin Plus Paclitaxel or Carboplatin Plus Pegylated Liposomal Doxorubicin (PLD) in Participants With Low CA125 Platinum-sensitive Ovarian Cancer
Condition: Platinum-Sensitive Ovarian Cancer in First Relapse
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Hypersensitivity; Recurrence
Intervention: Farletuzumab; Placebo
Intervention description: Farletuzumab will be administered intravenously (IV) weekly; Placebo will be administered intravenously (IV) weekly
Intervention MeSH terms: Farletuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 332.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ovarian Cancer in in first relapse; Platinum-Sensitive

Summary:

      MORAb-003-011 is a global, multicenter, double-blind, randomized placebo-controlled study to
      assess the safety and efficacy of farletuzumab in combination with standard chemotherapy in
      subjects with low cancer antigen 125 (CA125) platinum-sensitive ovarian cancer in first
      relapse.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Female subjects who are at least 18 years of age at the time of informed consent

          2. CA125 less than or equal to 3 x upper limit of normal (ULN) [105 units per millilitre
             (U/mL)] confirmed within 2 weeks of randomization using a centralized laboratory assay

          3. A histologically confirmed diagnosis of high-grade serous epithelial ovarian cancer
             including primary peritoneal and fallopian tube malignancies; all other histologies,
             including mixed histology, are excluded

          4. Have been treated with debulking surgery and a first-line platinum-based chemotherapy
             regimen

          5. Maintenance therapy during the first platinum-free interval is allowed; however, the
             last dose must have been at least 21 days prior to Randomization.

          6. Must be in a first relapse and have evaluable disease by Computed Tomography (CT) or
             Magnetic Resonance Imaging (MRI) scan, according to RECIST 1.1 (subjects with
             measurable disease per RECIST 1.1 or radiographically visible and evaluable disease).
             Subjects with only ascites or pleural effusion are excluded.

          7. Must have relapsed radiographically between 6 months and 36 months of completion of
             first-line platinum chemotherapy

          8. Must be a candidate for treatment with either carboplatin plus paclitaxel or
             carboplatin plus PLD with no medical contraindications present as outlined in the
             product labels for the selected regimen to be used in this study

          9. Have a life expectancy of at least 6 months, as estimated by the investigator

         10. Other significant medical conditions must be well-controlled and stable in the opinion
             of the investigator for at least 30 days prior to Randomization

         11. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

         12. Subjects being enrolled to receive paclitaxel plus carboplatin treatment must have
             neuropathic function (sensory and motor less than or equal to Grade 2 according to the
             National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE)
             v4.03 (2010)

         13. Laboratory results within the 2 weeks prior to Randomization must be as follows:

               -  Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L

               -  Platelet count greater than or equal to 100 x 10^9/L

               -  Hemoglobin greater than or equal to 9 g/dL

               -  Creatinine less than 1.5 x ULN (CTCAE Grade 1)

               -  Bilirubin less than 1.5 x ULN (CTCAE Grade 1)

               -  Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) less than 3 x
                  ULN

               -  Alkaline Phosphatase less than 2.5 x ULN (CTCAE Grade 1)

               -  Baseline albumin greater than or equal to Lower Limit of Normal

         14. Subjects of childbearing potential must be surgically sterile or consent to use a
             medically acceptable method of contraception throughout the study period. All females
             will be considered to be of childbearing potential unless they are postmenopausal (eg,
             amenorrheic for at least 12 consecutive months, in the appropriate age group, and
             without other known or suspected cause) or have been sterilized surgically (ie,
             bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with
             surgery at least 1 month before dosing). If a patient of childbearing potential is
             neither surgically sterile nor postmenopausal, a highly-effective contraceptive method
             (ie, a method that can achieve a failure rate of less than 1 percent (%) per year when
             used consistently and correctly) must start either before or at Screening and continue
             throughout the entire study period and for 6 months after the last dose of Test
             Article is administered. Pregnant and/or lactating females are excluded

        Exclusion Criteria:

          1. Known central nervous system (CNS) tumor involvement

          2. Evidence of other active invasive malignancy requiring treatment other than surgery in
             the past 3 years

          3. Clinically significant heart disease (eg, congestive heart failure of New York Heart
             Association Class 3 or 4 angina, not well controlled by medication, or myocardial
             infarction within 6 months)

          4. Electrocardiogram (ECG) demonstrating clinically significant arrhythmias that are not
             adequately medically managed (Note: subjects with chronic atrial arrhythmia, ie,
             atrial fibrillation or paroxysmal supraventricular tachycardia [SVT], are eligible)

          5. Active serious systemic disease, including active bacterial or fungal infection

          6. Active viral hepatitis or active human immunodeficiency virus (HIV) infection.
             Asymptomatic positive serology is not exclusionary.

          7. Other concurrent immunotherapy (eg, immunosuppressants or chronic use of systemic
             corticosteroids, with the exception that low-dose corticosteroids [50 mg/day
             prednisone or equivalent corticosteroid] are allowed; these should be discussed with
             the Medical Monitor)

          8. Known allergic reaction to a prior monoclonal antibody therapy or have any documented
             Anti-Drug Antibody (ADA) response; additionally known allergic reaction to the
             concomitant chemotherapies selected by the investigator for planned treatment in this
             study unless desensitization is planned

          9. Previous treatment with farletuzumab or other folate receptor targeting agents

         10. Previous treatment with cancer vaccine therapy

         11. For subjects being enrolled to receive PLD plus carboplatin, prior treatment with
             anthracyclines or anthracenodiones

         12. Breast-feeding, pregnant, or likely to become pregnant during the study

         13. Any medical or other condition that, in the opinion of the investigator, would
             preclude the subject's participation in a clinical study including medical
             contraindications as outlined in the product labels for the chemotherapies selected by
             the investigator for planned treatment in this study

         14. Patients who have had secondary debulking surgery or any second line therapy

         15. Currently enrolled in another clinical study or used any investigational drug or
             device within 30 days (or 5 x half-life for investigational drugs where the half-life
             is known) preceding informed consent