Whole Body Hyperthermia Combined With Chemotherapy in Treating Patients With Metastatic Breast, Ovarian, Endometrial, or Cervical Cancer

Study Overview
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Brief Summary
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RATIONALE: Hyperthermia therapy kills tumor cells by heating them to several degrees above body temperature. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with hyperthermia may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving fluorouracil and liposomal doxorubicin together with systemic hyperthermia works in treating patients with metastatic breast, ovarian, endometrial, or cervical cancer.

Detailed Description
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OBJECTIVES: Evaluate tumor response and toxicity induced by fluorouracil and doxorubicin HCl liposome combined with mild systemic hyperthermia in patients with metastatic breast, ovarian, endometrial, or cervical cancer. OUTLINE: This is a time-escalation study of systemic hyperthermia. Patients receive fluorouracil IV continuously over 24 hours on days 1-5 and doxorubicin HCl liposome IV over 30 minutes on day 6. Beginning on day 7, patients receive heat applied for 6-24 hours (in 6-hour sequential treatments) using a mild hyperthermia-induction device. Treatment repeats every 4-5 weeks for a total of 4 courses. Patients who achieve less than a complete response but have no disease progression may receive additional courses of chemotherapy alone. Cohorts of 5 patients receive escalating durations of hyperthermia until the recommended phase II duration is determined. The recommended phase II duration of hyperthermia is defined as the level preceding that at which 1 of 5 patients experiences measurable toxicity. (Phase I closed as of 9/28/01) Patients are followed at 4 weeks and then every 6 months for 1 year. PROJECTED ACCRUAL: A maximum of 34 patients will be accrued for this study within 48 months.

Official Title
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A Phase I-II Trial of Mild Whole-Body Hyperthermia Combined With Liposomal Doxorubicin/5-Fluorouracil in Patients With Advanced Malignancy

Conditions
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Breast Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer

Intervention / Treatment
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* Drug: fluorouracil
* Drug: pegylated liposomal doxorubicin hydrochloride
* Procedure: hyperthermia treatment


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed metastatic breast, ovarian, endometrial, or cervical carcinoma Measurable and evaluable disease No brain metastases No hepatic involvement greater than 80% No lung involvement greater than 30% Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: 18 and over Sex: Not specified Menopausal status: Not specified Performance status: Zubrod 0-2 Life expectancy: At least 12 weeks Hematopoietic: Absolute granulocyte count greater than 1,500/mm^3 Platelet count greater than 90,000/mm^3 Normal bone marrow cellularity on bone marrow biopsy Thrombin time less than 17 sec Fibrinogen greater than 200 mg/dL FSP less than 40 No coagulopathy Hepatic: Bilirubin less than 2.0 mg/dL SGPT less than 2 times normal PT less than 14 sec PTT less than 35 sec Renal: BUN less than 25 mg/dL Creatinine clearance at least 45 mL/min Cardiovascular: Normal cardiovascular system Resting ventricular ejection fraction greater than 40% No prior myocardial infarction No symptomatic coronary artery disease No unstable blood pressure No thromboembolic disease Neurologic: No seizures or other CNS disorders Negative computerized tomographic scan of brain Pulmonary: FEV_1 greater than 70% of predicted Arterial pressure of oxygen greater than 60 mmHg on room air with appropriate pressure of carbon dioxide and pH values No history of cardiopulmonary or respiratory disease Other: No other serious concurrent medical illness No diabetes mellitus PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Prior chemotherapy allowed Endocrine therapy: No adrenal corticosteroids Radiotherapy: Not specified Surgery: Not specified Other: No concurrent cardiac glycosides, antianginal therapy, or antiarrhythmics No concurrent vasodilators, anticoagulants, thrombolytic agents, or aspirin

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fluorouracil|nan|
|Drug: pegylated liposomal doxorubicin hydrochloride|nan|
|Procedure: hyperthermia treatment|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response |  |  | 
| Toxicity |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV breast cancer, recurrent breast cancer, recurrent cervical cancer, stage IVB cervical cancer, stage IVA cervical cancer, stage IV ovarian epithelial cancer, recurrent ovarian epithelial cancer, stage IV endometrial carcinoma, recurrent endometrial carcinoma, stage IV ovarian germ cell tumor, recurrent ovarian germ cell tumor, male breast cancer