An Efficacy and Safety Study of MORAb-003 in Platinum-Resistant or Refractory Relapsed Ovarian Cancer (FAR-122)

A Randomized, Double Blind, Placebo-Controlled Study of the Efficacy and Safety oF MORAb-003(Farletuzumab) in Combination With Paclitaxel Therapy in Subjects With Platinum-Resistant or Refractory Relapsed Ovarian Cancer

The study is being conducted to find out if paclitaxel works better when given together with an experimental drug called MORAb-003 (farletuzumab) or alone in patients with platinum-resistant or refractory relapsed ovarian cancer

Study Overview

• Status: Terminated
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: MORAb-003 (farletuzumab); Drug: 0.9% Saline

Detailed Description

Safety was assessed by the monitoring and recording of all adverse events (AEs), including drug hypersensitivity adverse events (DHAE), and serious adverse events (SAEs); clinical laboratory test (serum chemistry, hematology, urinalysis); tolerability (discontinuations, treatment delays, dose reductions); physical examinations (including vital signs assessment); 12-lead electrocardiograms (ECG) obtained in triplicate and reviewed by independent blinded cardiologist, and Karnofsky's performance status.

• Study Type: Interventional
• Enrollment (Actual): 415
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane & Women's Hospital
  • South Australia
    • Toorak Gardens, South Australia, Australia, 5064
      • The Burnside War Memorial Hospital, Inc.
  • Victoria
    • East Bentleigh, Victoria, Australia, 3165
      • Monash Medical Centre
    • Heidelburg, Victoria, Australia, 3084
      • Mercy Hospital for Women
    • Parkville, Victoria, Australia, 3052
      • The Royal Women's Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
    • Subiaco, Western Australia, Australia, 6008
      • St. John of God Hospital
• Belgium
  • Kortrijk, Belgium
    • AZ Greninge Hospital
  • Leuven, Belgium
    • University Hospitals Leuven
  • Liege, Belgium
    • CHU de Liège
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y5L3
      • BC Cancer Agency
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
• Netherlands
  • Groningen, Netherlands, 9700 RB
    • UMCG
  • Maastricht, Netherlands, 6229 HX
    • University Hospital Maastricht
  • Utrecht, Netherlands, 3584 CX
    • UMC Utrecht
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 07014
      • Hospital Universitario Son Dureta
    • Palma de Mallorca, Baleares, Spain, 07198
      • Hospital de Son Llàtzer
  • Barcelona
    • Mataro, Barcelona, Spain, 08304
      • Hospital de Mataro
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Taulis
    • Terrassa, Barcelona, Spain, 08227
      • Consorci Sanitari de Terrassa
  • Madrid
    • Alcorcon, Madrid, Spain, 28922
      • Fundación Hospital Alcorcón
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Southern Cancer Center
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
  • California
    • Greenbrae, California, United States, 94904
      • California Cancer Care, Inc.
    • La Jolla, California, United States, 92093
      • Moores UC San Diego Cancer Center
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
    • Monterey, California, United States, 93940
      • Monterey Bay Oncology
  • Florida
    • Jupiter, Florida, United States, 33458
      • Jupiter Medical Center
    • Miami, Florida, United States, 33179
      • Innovative Medical Research of South Florida, Inc.
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
  • Georgia
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Illinois
    • Winfield, Illinois, United States, 60190
      • Central DuPage Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Gynecologic Oncology
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Hematology And Oncology Specialists, Llc
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21237
      • Weinberg Cancer Institute at Franklin Square
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Morristown Memorial Hospital
  • New York
    • Brightwaters, New York, United States, 11718
      • Schwartz Gynecologic Oncology, PLLC
    • Lake Success, New York, United States, 11042
      • Arena Oncology Associates, PC
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10019
      • St. Luke's Roosevelt Hospital Center
  • North Carolina
    • Winston Salem, North Carolina, United States, 27103
      • Piedmont Hematology Oncology Associates, PA
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Middletown, Ohio, United States, 45042
      • Signal Point Clinical Research Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Cancer Care Associates
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Women's Hospital of UPMC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Harlingen, Texas, United States, 78550
      • International Beneficence Clinical Research, LLC
    • San Antonio, Texas, United States, 78229
      • South Texas Oncology & Hematology PA
    • Temple, Texas, United States, 76508
      • Scott & White Memorial Hospital And Clinic
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Northern Virginia Pelvic Surgery Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Diagnosis of non-mucinous epithelial ovarian cancer, including primary peritoneal and fallopian tube malignancies, measurable by CT or MRI scan assessed within 4 weeks prior to study entry
• Must have evidence of relapse by CA-125 (2xUpper Limit of Normal) or radiographically within 6 months of most recent platinum-containing chemotherapy. At least one of the lines of chemotherapy must have included a taxane.
• Must have been treated with debulking surgery and at least one line platinum-based chemotherapy;
• Subjects may have received up to four additional lines of chemotherapy after they developed platinum-resistance.
• Subjects must be candidate for repeat paclitaxel treatment

Exclusion Criteria:

• Clinical contraindications to use of paclitaxel, which include:

  1. persistent Grade 2 or greater peripheral neuropathy
  2. prior hypersensitivity reaction that persisted despite rechallenge with or without desensitization or resulted in bronchospasm or hemodynamic instability or was at least Grade 2 and resulted in medication discontinuation
• Current diagnosis of epithelial ovarian tumor of low malignant potential (borderline carcinomas). Note: EOC with prior diagnosis of a low malignant potential tumor that has been surgically resected is acceptable provided the subject did
• Prior radiation therapy is excluded with the exception that it is allowable only if measurable disease for ovarian cancer is completely outside the radiation portal
• Known allergic reaction to a prior monoclonal antibody therapy or have any documented human anti-human antibody (HAHA).
• Previous treatment with MORAb-003 (farletuzumab).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; MORAb-003 (Farletuzumab) Plus Paclitaxel	Drug: Paclitaxel; Other Names: Paclitaxel (80 mg/m^2) was administered by IV infusion over 1 hour following administration of FAR.; Drug: MORAb-003 (farletuzumab); Farletuzumab (FAR) at 2.5 mg/kg was administered by intravenous (IV) infusion weekly on Day 1 of Weeks 1 to 12 (Cycle 1) and then in 4-week cycles with treatment administered on Day 1 of Weeks 1 to 3 for all subsequent cycles.
Placebo Comparator: 2; Placebo Plus Paclitaxel	Drug: Paclitaxel; Other Names: Paclitaxel (80 mg/m^2) was administered by IV infusion over 1 hour following administration of FAR.; Drug: 0.9% Saline; Placebo (0.9% normal saline) was administered by IV infusion weekly on Day 1 of Weeks 1 to 12 (Cycle 1) and then in 4-week cycles with treatment administered on Day 1 of Weeks 1 to 3 for all subsequent cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS was defined as the time (in months) from the date of randomization to the date of the first observation of progression as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST), or death regardless of cause. If progression or death was not observed, the PFS time was censored at the date of the last tumor assessment without evidence of progression before the date of initiation of further antitumor treatment, or the cutoff date (whichever was earlier).	Date of Randomization to date of disease progression or death (whichever came first), assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months
Overall Survival (OS)	OS was defined as the time (in months) from the date of randomization to the date of death, whatever the cause. If death was not observed for a participant, the survival time was censored on the last date the participant was known to be alive or the cutoff date, whichever was earlier.	Date of Randomization to date of death, assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response	BOR was defined as the percentage of participants having either a confirmed complete response (CR) or confirmed partial response (PR) using modified RECIST criteria by independent radiologist review. RECIST criteria was adjusted based on current medical practices and on possible differences between ovarian cancer and other solid tumors. Tumor assessments performed up to the initiation of further antitumor treatment were considered. Target lesions selected for response assessment were measured using computed tomography (CT) or magnetic resonance imaging (MRI) scans then graded according to the modified RECIST criteria, adjusted based on current medical practices and on possible differences between ovarian cancer and other solid tumors. Participants were assigned to one of the categories of change in disease state; CR, PR, progressive disease (PD), stable disease ( S)D, or not evaluable (NE).	Date of first study drug to disease progression/recurrence, assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months
Time to Tumor Response (TTR)	TTR was derived for those participants with objective evidence of CR or PR, and was defined as the time (in months) from the date of randomization to the first documentation of object tumor response (TR). Analysis was based on the Kaplan-Meier estimated percentage of responders. This statistical analysis method measures the effect of study drug on tumor response over a period of time.	Date of Randomization to the first documentation of objective TR, assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival Based on Gynecologic Cancer InterGroup (GCIG)	Due to termination of the study, data were not collected and the outcome measure for PFS based on GCIG was not analyzed.	Length of study
Serologic Response Rate	Due to termination of the study, data were not collected and the outcome measure for Serologic Response Rate was not analyzed.	Length of study

Collaborators and Investigators

• Sponsor: Morphotek

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: August 18, 2008
• First Submitted That Met QC Criteria: August 18, 2008
• First Posted (Estimate): August 20, 2008

Study Record Updates

• Last Update Posted (Actual): March 30, 2017
• Last Update Submitted That Met QC Criteria: February 10, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: ovarian cancer; refractory ovarian cancer; relapsed ovarian cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel; Farletuzumab
• Other Study ID Numbers: MORAb003-003PR