Trastuzumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer

Study Overview
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Brief Summary
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Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Phase II trial to study the effectiveness of trastuzumab in treating patients who have stage III, stage IV, or recurrent endometrial cancer.

Detailed Description
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PRIMARY OOBJECTIVES: I. Determine the antitumor activity of trastuzumab (Herceptin), in terms of response, in patients with advanced, recurrent, or persistent endometrial adenocarcinoma that demonstrates HER2/neu gene amplification by fluorescent in situ hybridization. II. Determine the toxicity of this regimen in these patients. SECONDARY OBJECTIVES: I. Determine the progression-free and overall survival of patients treated with this regimen. II. Determine the effects of prognostic factors (i.e., initial performance status and histological grade) in patients treated with this regimen. OUTLINE: This is an open-label, multicenter study. Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 25-42 patients will be accrued for this study within 12 years.

Official Title
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A Phase II Evaluation of Trastuzumab (MoAb HER2) in Patients With Advanced, Recurrent or Persistent Endometrial Carcinoma With or Without Prior Chemotherapy

Conditions
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Endometrial Adenocarcinoma, ERBB2 Gene Amplification, Recurrent Uterine Corpus Carcinoma, Stage III Uterine Corpus Cancer AJCC v7, Stage IV Uterine Corpus Cancer AJCC v7

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Biological: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed endometrial adenocarcinoma Advanced, recurrent, or persistent disease Refractory to curative therapy HER2/neu gene amplification by fluorescent in situ hybridization Measurable disease Previously irradiated field as sole site of measurable disease allowed if evidence of progression since completion of radiotherapy Performance status - GOG 0-2 Absolute neutrophil count ? 1,500/mm^3 Platelet count ? 100,000/mm^3 Bilirubin ? 1.5 times upper limit of normal (ULN) Creatinine ? 1.5 times ULN LVEF ? 45% by echocardiogram or MUGA History of coronary artery disease and/or congestive heart failure allowed if medical management of condition has been stable within the past 6 months No active or unstable cardiac disease No active angina No myocardial infarction within the past 6 months No requirement for supplemental oxygen at rest or with ambulation Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection requiring antibiotics No uncontrolled infection No other invasive malignancy within the past 5 years except nonmelanoma skin cancer No other unstable medical condition that would preclude study participation At least 3 weeks since prior biologic and immunologic agents directed at the malignant tumor No prior anti-HER2 monoclonal antibody preparation No other concurrent immunotherapy Recovered from prior chemotherapy Multiple prior chemotherapy regimens allowed No more than 320 mg/m^2 total dose of prior doxorubicin allowed (including doxorubicin HCl liposome or other liposomally encapsulated doxorubicin preparations) No concurrent chemotherapy At least 1 week since prior hormonal therapy directed at the malignant tumor No concurrent hormonal therapy Continuation of hormone replacement therapy allowed See Disease Characteristics At least 3 weeks since prior radiotherapy for the malignant tumor and recovered No concurrent radiotherapy Recovered from prior recent surgery At least 3 weeks since any prior therapy directed at the malignant tumor No prior cancer treatment that would contraindicate study therapy

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (trastuzumab)<br>Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Biological: Trastuzumab<br>* Given IV<br>* Other names: Trazimera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and duration of objective response |  | Up to 5 years | 
| Frequency and severity of observed adverse effects assessed using Common Terminology Criteria (CTC) version 2.0 |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of progression-free survival | Will be evaluated with non-parametric statistics (such as the log-rank test) through comparisons with the historical controls. | From study entry until disease progression, death or date or last contact, assessed up to 5 years | 
| Duration of overall survival | Will be evaluated with non-parametric statistics (such as the log-rank test) through comparisons with the historical controls. | From study entry to death or date or last contact, assessed up to 5 years | 
| Prognostic factors (i.e., initial performance status and histological grade) | Comparisons will be made through a Cox model, which allows for adjustments with the prognostic variables. | Not Provided |