Clinical Trial 18190

Cancer Type: Gynecological Tumor
Interventions:Doxil (doxorubicin liposome); Farletuzumab; Paraplatin (carboplatin); Placebo; Taxol (paclitaxel); carboplatin; doxorubicin liposome; paclitaxel

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Robert Wenham

Overview

Study Title

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Efficacy and Safety of Farletuzumab (MORAb-003) in Combination with Carboplatin plus Paclitaxel or Carboplatin plus Peglyated Liposomal Doxorubicin (PLD) in Subjects with Low CA125 Platinum-Sensitive Ovarian Cancer

Summary

This research is being done to find out if carboplatin plus paclitaxel or carboplatin plus Pegylated Liposomal Doxorubicin (PLD), chemotherapies (anticancer drugs) that are used to treat ovarian cancer, work better alone or when given with an investigational drug called farletuzumab.

Objective

Primary: The primary objective of the study is to demonstrate that farletuzumab has superior efficacy compared to placebo in improving progression-free survival (PFS) as determined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 when added to 1 of 2 standard chemotherapy regimens (carboplatin plus paclitaxel or carboplatin plus PLD) in subjects with platinum-sensitive ovarian cancer in first relapse who have a cancer antigen 125 (CA125) <= 3x the upper limit of normal (ULN) (105 U/mL) at study entry. Secondary: To assess the effect of farletuzumab on overall survival (OS) in this population. To assess the effect of farletuzumab in prolonging second platinum-free interval longer than first platinum-free interval. To assess the effect of farletuzumab on best objective response (OR) rate, time to response (TTR) and duration of response (DR) by RECIST 1.1 criteria. To assess the safety and tolerability of farletuzumab. To assess the pharmacokinetics and exposure-response relationships between farletuzumab and PFS and OS. Exploratory: To explore blood CA125 change pattern during study. To explore biomarkers that may correlate with the efficacy-related endpoints and farletuzumab mechanism of action. To explore expression of CA125 and folate receptor alpha in blood, urine, and tissue to correlate to disease characteristics, exposure, efficacy-related endpoints, farletuzumab mechanism of action, and other biomarkers.

Inclusion Criteria

  • Females who are at least 18 years of age at the time of informed consent.
  • CA125 less than or equal to 3 x upper limit of normal (ULN) (10^5 U/mL) confirmed within 2 weeks of randomization using a centralized laboratory assay.
  • 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.
  • Have been treated with debulking surgery and a first-line platinum-based chemotherapy regimen.
  • Maintenance therapy during the first platinum-free interval is allowed; however, the last dose must have been at least 21 days prior to Randomization. No cancer vaccine therapy is allowed.
  • Must have evaluable disease by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan, according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Potential participants with only ascites or pleural effusion are excluded.
  • Must have relapsed radiographically between 6 months and 36 months of completion of first-line platinum chemotherapy and should be randomized within 16 weeks of radiographic relapse.
  • Must be a candidate for treatment with either carboplatin plus paclitaxel or carboplatin plus PLD.
  • A life expectancy of at least 6 months, as estimated by the investigator.
  • Other significant medical conditions must be well-controlled and stable in the opinion of the investigator for at least 30 days prior to Randomization.
  • Have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
  • Potential participants 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).
  • Adequate laboratory results within the 2 weeks prior to Randomization.
  • Women of childbearing potential must be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period. Pregnant and/or lactating females are excluded.
  • Must provide written informed consent and be willing and able to comply with all aspects of the protocol.

  • Exclusion Criteria

  • Known central nervous system (CNS) tumor involvement.
  • Evidence of other active invasive malignancy requiring treatment other than surgery in the past 3 years.
  • Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class 3 or 4 angina, not well controlled by medication, or myocardial infarction within 6 months).
  • Electrocardiogram (ECG) demonstrating clinically significant arrhythmias that are not adequately medically managed (Note: potential participants 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 viral hepatitis or active human immunodeficiency virus (HIV) infection. Asymptomatic positive serology is not exclusionary.
  • Other concurrent immunotherapy (e.g., 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).
  • Known allergic reaction to a prior monoclonal antibody therapy or have any documented Anti-Drug Antibody (ADA) response.
  • Previous treatment with farletuzumab or other folate receptor targeting agents.
  • For potential participants being enrolled to receive PLD plus carboplatin, prior treatment with anthracyclines or anthracenodiones.
  • Breast-feeding, pregnant, or likely to become pregnant during the study.
  • Any medical or other condition that, in the opinion of the investigator, would preclude participation in a clinical study.
  • Have had secondary debulking surgery.
  • 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.