Whole-Abdominal Radiation Therapy and Cisplatin in Treating Patients With Stage III or Stage IV Endometrial Cancer That Has Been Removed by Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Radiation therapy may also make tumor cells more sensitive to cisplatin. Giving radiation therapy together with cisplatin after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase I trial is studying the side effects and best dose of whole-abdominal radiation therapy when given together with cisplatin in treating patients with stage III or stage IV endometrial cancer that has been removed by surgery.

Detailed Description
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OBJECTIVES: Determine a recommended phase II dose of adjuvant whole-abdominal radiotherapy when administered with cisplatin in patients with optimally debulked stage III or IV carcinoma of the endometrium. OUTLINE: This is a dose-escalation study of whole-abdominal radiotherapy (WAR). Patients receive 3 courses of standard chemotherapy comprising carboplatin IV and paclitaxel IV. Beginning within 6 weeks after completion of standard chemotherapy, patients receive cisplatin IV over 30-60 minutes and undergo a single fraction of WAR on day 1. Treatment with cisplatin and WAR repeats weekly for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo standard vaginal brachytherapy beginning no earlier than the last course of standard chemotherapy or no later than 1 week before the start of cisplatin and WAR. Cohorts of 3-6 patients receive escalating doses of WAR until the recommended phase II dose (RPTD) is determined. The RPTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the RPTD. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Official Title
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A Phase I Study Using Abdominal Radiotherapy as a Cisplatin Chemosensitizer for Optimally Debulked Stage III/IV Carcinoma of the Endometrium

Conditions
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Endometrial Cancer

Intervention / Treatment
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* Radiation: Vaginal Brachytherapy
* Drug: Cisplatin
* Radiation: Whole Abdominal Radiation [WAR] Therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of endometrial cancer, including any of the following cellular types: Papillary serous carcinoma Clear cell carcinoma Adenocarcinoma Stage III or IV disease No evidence of extra-abdominal extension of disease (e.g., groin nodes, lung, or supraclavicular nodes) Has undergone total-abdominal hysterectomy, surgical removal of any present fallopian tube and ovary, and resection of any palpable lymph nodes in the pelvis and para-aortic region (or surgical sampling of these nodal regions if no palpable nodes were present) within the past 6 weeks Peritoneal washings must have been collected for cytological evaluation Must have ≤ 1 cm residual disease after surgery PATIENT CHARACTERISTICS: Karnofsky performance status 60-100% Life expectancy ≥ 6 months WBC ≥ 3,000/mm^3 Granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Creatinine < 2.0 mg/dL Bilirubin < 1.5 times upper limit of normal (ULN) Lactate dehydrogenase < 3 times ULN Gamma glutamyl transferase < 3 times ULN SGPT and SGOT < 3 times ULN Alkaline phosphatase < 3 times ULN No other malignant tumor within the past 5 years PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior radiotherapy to the whole abdomen and/or pelvis/vagina No systemic chemotherapy within the past 5 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Whole-Abdominal Radiation Therapy and Chemotherapy<br> | Radiation: Vaginal Brachytherapy<br>* High-Dose Rate [HDR] or Low-Dose Rate [LDR], no earlier than during last cycle of Carboplatin/Taxol chemotherapy; or no later than 1 week before cisplation and WAR therapy<br>Drug: Cisplatin<br>* Weekly at 40 mg/m2 (maximum of 70 mg) for 6 weeks, start no later than 6 weeks from last cycle of standard of care carboplatin and taxol chemotherapy<br>Radiation: Whole Abdominal Radiation [WAR] Therapy<br>* Whole Abdominal Radiation Therapy, Dose Escalated [2-Levels]; 6 -8 hours after administration of Cisplatin chemotherapy<br>* Other names: WAR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as assessed by GOG Common Toxicity Criteria |  | Study duration | 
| Recommended phase II dose of whole-abdominal radiotherapy |  | Study duration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endometrial adenocarcinoma, endometrial clear cell carcinoma, endometrial papillary carcinoma, stage III endometrial carcinoma, stage IV endometrial carcinoma