Evaluation of Carboplatin/Paclitaxel With and Without Trastuzumab (Herceptin) in Uterine Serous Cancer

Study Overview
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Brief Summary
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The primary objective of this study is to estimate whether the addition of trastuzumab to paclitaxel and carboplatin chemotherapy improves progression free survival when compared to paclitaxel and carboplatin alone in Uterine Serous Papillary Carcinoma (USPC) patients overexpressing Her2/neu at 3+ level by immunohistochemistry (IHC)or positive by fluorescence in situ hybridization (FISH).

Detailed Description
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The purpose of this study is to perform a randomized Phase II evaluation of Carboplatin/Paclitaxel with or without Trastuzumab (Herceptin) in patients with HER2/neu+ advanced stage/recurrent disease with an emphasis on determining the progression free survival in USPC patients and assessing immunologic markers predictive of trastuzumab response.

Official Title
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Randomized Phase II Evaluation of Carboplatin/Paclitaxel With and Without Trastuzumab (Herceptin) in HER2/Neu+ Patients With Advance/Recurrent Uterine Serous Papillary Carcinoma

Conditions
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Endometrial Cancer

Intervention / Treatment
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* Drug: Carboplatin/Paclitaxel
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have advanced (stage III-IV) or recurrent histologically confirmed USPC with measurable disease. Patients must harbor a tumor HER2/neu+ based upon IHC staining score of 3+ or 2+ with confirmed gene amplification by FISH Exclusion Criteria: Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancers, significant history of cardiac disease, uncontrolled hypertension, unstable medical issue, brain leptomeningeal, prior therapy with trastuzumab, uncontrolled seizure disorder, seropositive for HIV, active hepatitis, hemorrhagic diathesis or requiring supplemental oxygen.
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 |
| --- | --- |
| Active Comparator: Carboplatin/Paclitaxel<br>Chemotherapy | Drug: Carboplatin/Paclitaxel<br>* Paclitaxel 175 mg/m2 will administered intravenously every 21 days for 6 cycles. Carboplatin AUC 5 will be administered intravenously every 21 days for 6 cycles. 100% of patients will receive Carboplatin/Paclitaxel.<br>* Other names: cis-Diammine;|
| Experimental: Trastuzumab<br>Monoclonal antibody | Drug: Trastuzumab<br>* Paclitaxel 175 mg/m2 will be administered intravenously every 21 days for 6 cycles. Carboplatin AUC 5 will be administered intravenously every 21 days for 6 cycles. On day 1, an 8 mg/kg loading dose of trastuzumab will be administered over a 90 minute period. Beginning on day 21, patients will receive 6mg/kg of trastuzumab, administered intravenously every 21 days and continued indefinitely every 21 days after 6 cycles of cytotoxic therapy are completed and until progression of the disease or prohibitive toxicities occur. 50% of patients will receive Carboplatin/Paclitaxel with the addition of Trastuzumab.<br>* Other names: Herceptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival Differences Between Treatment Arms. | Progression free survival differences between treatment arms. | 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Assess the Safety Profile of Trastuzumab in USPC Patients by CTCAE v4.0 | To assess the safety profile of trastuzumab in USPC patients by CTCAE v4.0. Presented are counts of those that experience any Serious Adverse Events or All Other Adverse Events. | 6 years | 
| To Assess Objective Response Rate (ORR) | To assess objective response rate (ORR) | 6 years | 
| To Assess Overall Survival (OS) | To assess overall survival (OS), presented are the number of participants that survived through the duration of the study period. | 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uterine serous papillary carcinoma, Type II endometrial cancer, HER2/neu, Paclitaxel, Carboplatin, Trastuzumab