Efficacy and Safety of Farletuzumab (MORAb-003) in Combination With Carboplatin and Taxane in Participants With Platinum-sensitive Ovarian Cancer in First Relapse

Phase 3TerminatedNCT00849667

Morphotek1,100 enrolled

Overview

This research is being done to find out if Carboplatin and Taxane works better alone or when given with an experimental drug called MORAb-003(farletuzumab) in subjects with first platinum sensitive relapsed ovarian cancer.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

1,100

Conditions

Ovarian Cancer

Interventions

FarletuzumabDRUG

Farletuzumab IV infusion.

CarboplatinDRUG

Carboplatin IV infusion.

TaxaneDRUG

Taxane (Paclitaxel or Docetaxel) IV infusion.

Farletuzumab-matched placebo

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * A histologically or cytologically confirmed diagnosis of non-mucinous epithelial ovarian cancer including primary peritoneal or fallopian tube malignancies * Must have measurable disease by CT or MRI scan * Must have relapsed radiologically with a randomization date within ≥6 and \< 24 months of completion of first-line platinum chemotherapy * Have been treated with debulking surgery and first-line platinum and taxane based chemotherapy. * Prior bevacizumbab maintenance is allowed. The last dose of bevacizumab must have been at least 30 days before study Day 1. No cytotoxic maintenance therapy (e.g. taxane) or cancer vaccine therapy is allowed. * Must be a candidate for carboplatin and taxane therapy * Neurologic function: neuropathy (sensory and motor) ≤CTCAE Grade 1 Exclusion Criteria: * Subjects who never responded to first-line platinum-based therapy or whose first relapse occurs \<6 months or \>24 months from the last platinum therapy * Subjects who have received other therapy to treat their ovarian cancer since relapse * Known central nervous system (CNS) tumor involvement * Evidence of other active invasive malignancy requiring treatment in the past 5 years * Known allergic reaction to a prior monoclonal antibody therapy or have any documented HAHA * Previous treatment with MORAb-003 (farletuzumab) * Clinical contraindications to use of a taxane

Locations (375)

Outcomes

Primary Outcomes

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 based on the independent radiologic assessment (modified response evaluation criteria in solid tumors \[RECIST\]), or date of death, whatever the cause. As per RECIST, disease progression was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. If progression or death was not observed for a participant, 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).

Time frame: From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)

Secondary Outcomes

Overall Survival (OS)

OS was defined as the time (in months) from the date of randomization to the date of death, due to any 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.

Time frame: From the date of randomization until date of death from any cause, or study termination by sponsor, whichever came first (up to 48 months)

Cancer Antigen-125 (CA-125) Progression-Free Survival

CA-125 PFS was defined as the time (in months) from the date of randomization until the date of the first observation of progression based on the Rustin criteria, or date of death, whatever the cause. If progression or death was not observed for a participant, the CA-125 PFS time was censored at the date of the last CA-125 assessment without evidence of progression before the date of initiation of further antitumor treatment or the "primary analysis cut off" date, whichever was earlier. Based on Rustin criteria, progressive disease (PD) was a rise in CA125 since beginning of consolidation or previously normal CA125 that rises to greater than or equal to (\>=) 2 multiple (\*) ULN with either event documented on two occasions or CA-125 \>=2\*nadir value with either event documented on two occasions.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Farletuzumab-matched placebo IV infusion.

University Of Alabama At Birmingham

Birmingham, Alabama, United States

Oncology Specialties, PC

Huntsville, Alabama, United States

Arizona Hematology & Oncology Associates

Phoenix, Arizona, United States

St. Joseph's Hospital, Barrow Neurology Clinics

Phoenix, Arizona, United States

Arizona Oncology Associates

Tucson, Arizona, United States

Arizona Cancer Center

Tucson, Arizona, United States

Providence St. Joseph Medical Center

Burbank, California, United States

California Cancer Care, Inc.

Greenbrae, California, United States

University of California San Diego

La Jolla, California, United States

University of California Los Angeles Medical Center

Los Angeles, California, United States

...and 365 more locations

Time frame: From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)

Progression-Free Survival Based on Gynecologic Cancer InterGroup (GCIG) Criteria

PFS using GCIG criteria was defined as time (in months) from date of randomization until date of first observation of progression based on GCIG criteria, or date of death, whatever the cause. If progression or death was not observed for a participant, GCIG PFS time was censored at later date of last tumor assessment or CA-125 assessment without evidence of progression before date of initiation of further antitumor treatment or the "primary analysis cut off" date, whichever was earlier. Disease progression per GCIG: Participants with elevated CA-125 pretreatment and normalisation of CA-125 must show evidence of CA-125 \>=two times ULN on two occasions at least one week apart or participants with elevated CA-125 pretreatment, which never normalises must show evidence of CA-125 \>=two times nadir value on two occasions at least one week apart or participants with CA-125 in normal range pretreatment must show evidence of CA-125 \>=two times ULN on two occasions at least one week apart.

Time frame: From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)

Percentage of Participants With Length of Second Remission Greater Than First Remission

Length of first remission was defined as a.) the period of time (in months) from the date of completion of previous platinum-based chemotherapy until date of first relapse (that is, first observation of progression). It was assumed that the date of first relapse was the earlier of progression by CA-125 or progression by radiologic assessment, as judged by the investigator using GCIG criteria. b.) the period of time (in months) from the date of completion of previous platinum-based chemotherapy (used prior to study entry) until date of randomization. The length of the second remission was defined as the period of time (in months) from the date of completion of platinum-based chemotherapy until the first observation of progression based on GCIG criteria. Based on GCIG criteria, disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.

Time frame: From the date of last dose of platinum-based chemotherapy to date of relapse and date of last dose of platinum-based chemotherapy to first observation of progression (up to 48 months)

Percentage of Participants With Objective Response

Objective response was defined as either a confirmed complete response (CR) or confirmed partial response (PR) as assessed by investigator based on response evaluation criteria in solid tumors version 1.1 (RECIST version 1.1). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.

Time frame: From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 48 months)

Duration of Tumor Response

Duration of response was defined as the time (in months) from first documentation of objective response (confirmed CR or PR) to the first documentation of objective tumor progression or death due to any cause. Duration of response was derived only for those participants with objective evidence of confirmed CR or PR.

Time frame: From the first date of confirmed objective response (CR or PR) to first date of progression or death due to any cause (up to 48 months)

Time to Tumor Response (TTR)

Time to tumor response was defined as the time (in months) from the date of randomization to first documentation of objective tumor response. Time to tumor response was derived for those participants with objective evidence of CR or PR.

Time frame: From the date of randomization to first documentation of objective response (up to 48 months)

Percentage of Participants With Serologic Response (SR)

SR was defined as either normalization, 75% response, or 50% response using the Rustin criteria. Percentage of participants with 50% SR, 75% SR and SR leading to normalization were reported. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of four CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level). A 75% response was established if there had a serial decrease in serum CA-125 levels of 75% over three samples. In both the 50% and 75% response definitions, the final sample was analyzed at least 28 days after the previous sample.

Time frame: Up to 48 months

Duration of 50% Serologic Response

Duration of SR was defined as the time (in months) from first documentation of response to the first documentation of 50% serologic progression or death due to any cause. For responding participants who did not have serologic progression or did not die and who 1) were either still on study at the time of an analysis, 2) were given antitumor treatment other than study treatment, or 3) were withdrawn from study follow-up before documentation of serologic progression, the duration of SR was censored at the last date the participant was known to be without serologic progression. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of three CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level).

Time frame: From the first date of documentation of response to first documentation of serologic progression or death due to any cause (up to 48 months)

Time to 50% Serologic Response (TSR)

TSR was defined as the time (in months) from the date of randomization to first documentation of 50% SR. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of three CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level).

Time frame: From the date of randomization to first documentation of 50% SR (up to 48 months)

Percentage of Participants With Clinical Benefit

Clinical benefit was defined as a confirmed CR or a confirmed PR, or stable disease (SD) using RECIST 1.0 criteria. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non target lesions.

Time frame: Up to 48 months

Cmax: Maximum Observed Plasma Concentration of Total Carboplatin and Total Paclitaxel