Clinical trial NCT02289950: 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
Official 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 Pegylated Liposomal Doxorubicin (PLD) in Subjects With Low CA125 Platinum-Sensitive Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Platinum-Sensitive Ovarian Cancer in First Relapse
Keywords: Ovarian Cancer in in first relapse
Platinum-Sensitive
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2014-11-13
Enrollment: 332
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: Participants will be enrolled into 1 of 2 chemotherapy treatment arms at the investigator's discretion: carboplatin plus paclitaxel or carboplatin plus Pegylated Liposomal Doxorubicin (PLD), and then randomized in a 2:1 ratio to receive weekly farletuzumab 5 mg/kg or placebo (ie, Test Article). All participants will receive a loading dose for the first 2 weeks of 10 mg/kg Test Article (farletuzumab or placebo). Participants will be stratified at randomization by individual chemotherapy treatment regimen (targeted 1:1 ratio) and platinum-free interval following first-line therapy (6 to 12 months vs greater than 12 to 36 months).

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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From the date of randomization to the date of first documentation of PD, or date of death, whichever occurs first up to approximately 5 years 5 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From the date of randomization until the date of death (up to approximately 5 years 5 months)
measure: Number of Participants With Best Overall Response (BOR)
timeFrame: From first dose of study drug (Baseline) up to approximately 5 years 5 months
measure: Time to Tumor Response (TTR)
timeFrame: From the date of randomization until date of first observation of response (CR or PR) up to approximately 5 years 5 months
measure: Duration of Response (DOR)
timeFrame: From date of the first observation of CR or PR until the date of first observation of progression or date of death up to approximately 5 years 5 months
measure: Percentage of Participants Achieving Each Second Platinum-Free Interval Stratified by First Platinum-Free Interval
timeFrame: From the date of randomization to the date of first relapse (or first observation of progression/death) up to approximately 5 year 5 months
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Orange
country: United States
state: California
city: Roseville
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Miami
country: United States
state: Florida
city: Miramar
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Augusta
country: United States
state: Georgia
city: Savannah
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Grand Island
country: United States
state: Nebraska
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Centerville
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Chattanooga
country: United States
state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Annandale
country: United States
state: Virginia
city: Charlottesville
country: United States
state: Virginia
city: Edegem
country: Belgium
state: Antwerpen
city: Brussels
country: Belgium
state: Bruxelles
city: Hasselt
country: Belgium
state: Limburg
city: Gent
country: Belgium
state: Oost-Vlaanderen
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Ulm
country: Germany
state: Baden-Württemberg
city: Chemnitz
country: Germany
state: Sachsen
city: Berlin
country: Germany
city: Dresden
country: Germany
city: Essen
country: Germany
city: Napoli
country: Italy
state: Campania
city: Roma
country: Italy
state: Lazio
city: Bari
country: Italy
state: Puglia
city: Avellino
country: Italy
city: Bologna
country: Italy
city: Milano
country: Italy
city: Napoli
country: Italy
city: Perugia
country: Italy
city: Chuo-Ku
country: Japan
city: Hidaka-City
country: Japan
city: Kashiwa-City
country: Japan
city: Koto-Ku
country: Japan
city: Kurume-City
country: Japan
city: Matsuyama-City
country: Japan
city: Minato-Ku
country: Japan
city: SuntoGun
country: Japan
city: Palma de Mallorca
country: Spain
state: Baleares
city: Cordoba
country: Spain
state: Córdoba
city: Madrid
country: Spain
city: Sabadell
country: Spain
city: Plymouth
country: United Kingdom
state: Devon
city: London
country: United Kingdom
Study officials:
References: