A Study to Evaluate the Effect of the Combination of Pertuzumab With Carboplatin-Based Standard Chemotherapy in Patients With Recurrent Ovarian Cancer

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of pertuzumab in combination with carboplatin-based standard chemotherapy in patients with platinum-sensitive recurrent ovarian cancer. The anticipated time on study treatment is 3-12 months.

Official Title
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A Randomized, Open-label Study of the Effect of Omnitarg in Combination With Carboplatin-based Chemotherapy Versus Carboplatin-based Therapy Alone on Treatment Response in Patients With Platinum-sensitive Recurrent Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: pertuzumab
* Drug: paclitaxel
* Drug: gemcitabine
* Drug: carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed ovarian, primary peritoneal, or fallopian tube cancer; only 1 previous regimen, which must be platinum-based; platinum-sensitive disease which is defined by a progression-free interval of greater than 6 months after completion of platinum-based chemotherapy. Exclusion Criteria: previous radiotherapy; previous treatment with an anti-cancer vaccine or any targeted therapy; major surgery or traumatic injury within 4 weeks of study; history or evidence of central nervous system metastases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy + Pertuzumab<br> | Drug: pertuzumab<br>* Loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks<br>Drug: paclitaxel<br>* 175 mg/m2 IV every 3 weeks for 6 cycles<br>Drug: gemcitabine<br>* 1000 mg/m2 IV Day 1 and 8 of each cycle for 6 cycles<br>Drug: carboplatin<br>* Target AUC of 5 following paclitaxel or AUC of 4 following gemcitabine IV every 3 weeks for 6 cycles<br>|
| Active Comparator: Chemotherapy<br> | Drug: paclitaxel<br>* 175 mg/m2 IV every 3 weeks for 6 cycles<br>Drug: gemcitabine<br>* 1000 mg/m2 IV Day 1 and 8 of each cycle for 6 cycles<br>Drug: carboplatin<br>* Target AUC of 5 following paclitaxel or AUC of 4 following gemcitabine IV every 3 weeks for 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disease Progression or Death | Disease progression was assessed according to RECIST (Response Evaluation Criteria In Solid Tumors), for participants with measurable disease, or by changes in CA 125 (Cancer Antigen 125) according to GCIG (Gynecologic Cancer Inter Group) for all participants. Participants who did not progress or died while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment. | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks | 
| Progression-Free Survival | Progression-free survival was defined as the time from first administration of study drug (Study Day 1) to documented disease progression or death, whichever occurred earlier. Disease progression was assessed according to RECIST, for participants with measurable disease, or by changes in CA 125 according to GCIG for all participants. Participants who did not progress or died while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment. | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks | 
| Kaplan-Meier Probability of No Disease or Progression at 1 Year | The probability of being event free (no disease progression or death events) at 1 year in participants remaining at risk. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Best Overall Confirmed Response Based on Combined CA 125 and RECIST Measurements | Response by tumor measurement occurred if there was documented and confirmed complete response (CR) or partial response (PR). For all participants, response was assessed by both the RECIST and by CA 125 levels, according to whether the participant had measurable or non-measurable disease at baseline. Response according to CA 125 levels was defined as at least a 50% reduction from baseline. The decrease had to be confirmed and maintained for at least 28 days. The confirmatory sample must have been less than or equal to the previous sample (within an assay variability of 10%). For overall response, the response categories were response, stable disease and progressive disease. Stable disease included 1) stable disease as defined by RECIST for solid tumors and 2) CA 125 levels that had not met the definition of response or progressive disease. | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks | 
| Duration of Response | For participants who achieved a response, the duration of response was defined as the interval between initial documentation of response to the first documentation of disease progression or death. Participants who responded and did not progress or die while on study or while being followed were censored at the last valid tumor or CA 125 measurement. | Day 15 of Cycles 2, 4, 6, and Day 15 of all Cycles from Cycle 7 to 17 until disease progression up to 104 weeks | 
| Kaplan-Meier Probability of Maintaining a Response to at Least 1 Year |  | 1 year | 
| Percentage of Participants With Disease Progression | Disease progression was assessed according to RECIST, for participants with measurable disease, or by changes in CA 125 according to GCIG for all participants. Participants who did not progress while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment. | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression | 
| Time to Progressive Disease | The time to progressive disease is the interval of time from date of first dose of study medication to date of first documentation of progressive disease by either RECIST or CA 125 criteria. Participants who never progressed while being followed were censored at the last valid tumor measurement or CA 125 measurement. | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression | 
| Kaplan-Meier Probability of Being Progression Free at 1 Year |  | 1 year | 
| Time To Response | Time to response was the date of first dose of study medication to the date of the first documentation of response, according to CA 125 criteria for all participants or response according to RECIST criteria for participants with measurable disease. If response was evaluable by both criteria, then the date of response was for the earlier of the two events. | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment | 
| Percentage of Participants Who Died |  | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment | 
| Overall Survival | Survival was the interval of time from date of first dose of study medication to date of death at any time. Participants who had not died were censored at the date of last contact when they were known to be alive. | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment | 
| Kaplan-Meier Probability of Being Alive at 1 Year |  | 1 year |