Combination Chemotherapy With or Without Whole-Body Hyperthermia in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Hyperthermia therapy kills tumor cells by heating them to several degrees above body temperature. Combining hyperthermia with chemotherapy may kill more tumor cells. It is not yet known if chemotherapy is more effective with or without whole-body hyperthermia therapy in treating gynecologic cancer. PURPOSE: Randomized phase II/III trial to compare the effectiveness of chemotherapy with or without whole-body hyperthermia in treating patients who have recurrent ovarian epithelial, fallopian tube, or peritoneal cancer.

Detailed Description
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OBJECTIVES: Compare the time to progressive disease in patients with recurrent ovarian epithelial, fallopian tube, or extraovarian peritoneal cancer treated with carboplatin and ifosfamide with or without whole body hyperthermia. Compare the response rate, duration of response, and survival time of patients treated with these regimens. Compare the effect on the presence of disseminated tumor cells in bone marrow in patients treated with these regimens. Compare the toxicity of these regimens in these patients. Assess quality of life of patients treated with these regimens. OUTLINE: This is a phase II safety and efficacy study followed by a phase III randomized, open-label, multicenter study. Phase II: Patients receive ifosfamide IV over 1 hour and carboplatin IV over 20 minutes on day 1. Patients also undergo whole body hyperthermia for at least 1 hour on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Phase III (after successful treatment of 15 patients in phase II): Patients are stratified according to disease-free interval (6-12 months vs more than 12 months), measurable disease (bidimensionally measurable vs measurable by other clinical means), and disease recurrence (first recurrence vs second or greater recurrence). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive ifosfamide, carboplatin, and whole body hyperthermia as in phase II. Arm II: Patients receive ifosfamide and carboplatin as in arm I. In both arms, treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed before each course, 4 weeks after the last course, and then every 3 months for 2 years. Patients are followed at 4 weeks and then every 3 months for 2 years. PROJECTED ACCRUAL: A total of 15 patients will be accrued for phase II of this study. A total of 226 patients (113 per treatment arm) will be accrued for phase III of this study within 2 years.

Official Title
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A Randomized Phase II/III Trial Comparing Carboplatin-Ifosfamide (IC)-Chemotherapy Vs. IC-Chemotherapy Combined With Extreme Whole Body Hyperthermia In Patients With Recurrence Of Epithelial Ovarian Carcinoma: DOLPHIN-1-STUDY

Conditions
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Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: ifosfamide
* Procedure: hyperthermia treatment


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed ovarian epithelial, fallopian tube, or extraovarian peritoneal cancer Recurrent disease (any FIGO stage) Not amenable to curative surgery or radiotherapy alone Failed prior primary platinum-based therapy at least 6 months after therapy discontinuation Measurable lesion by CT scan, MRI, chest x-ray, or sonography Physical examination allowed for documenting lymph node and skin metastases Physical gynecological examination allowed for well-defined palpable tumor lesions Increase in CA 125 without any measurable tumor is not acceptable as indication of recurrence No CNS metastases No tumor of borderline malignancy PATIENT CHARACTERISTICS: Age 18 to 65 Performance status ECOG 0-2 Life expectancy At least 24 weeks Hematopoietic Neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic Not specified Renal Creatinine clearance at least 60 mL/min No chronic or acute renal failure Cardiovascular Cardiovascular function sufficient for hyperthermia treatment by stress-ECG No cardiomyopathy with impaired ventricular function No New York Heart Association class III or IV heart disease No cardiac arrhythmias influencing LVEF and requiring medication No myocardial infarction or angina pectoris within the past 6 months No uncontrolled arterial hypertension Pulmonary Pulmonary function sufficient for hyperthermia treatment by pulmonary function tests Other No untreated endocrinological disease (e.g., hyperthyroidism or diabetes mellitus) No other primary malignancy except carcinoma in situ of the cervix or adequately treated basal cell skin cancer No contraindication against hyperthermia treatment (e.g., photodermatosis, history of malignant hyperthermia, or claustrophobia) No hypersensitivity to carboplatin, ifosfamide, or any other study medication Not pregnant or nursing PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics No concurrent cytotoxic or other antineoplastic therapy Endocrine therapy Concurrent hormone replacement therapy allowed Concurrent steroid antiemetics allowed Radiotherapy See Disease Characteristics At least 1 year since prior radiotherapy (tumoricidal dose) of the pelvis Concurrent palliative local radiotherapy for painful (nonprogressive) existing lesion is allowed if other measurable sites are present No concurrent radiotherapy to a second existing lesion Surgery See Disease Characteristics Other No prior form of hyperthermic therapy At least 3 weeks since other medications as part of another clinical study At least 3 weeks since prior investigational agents At least 6 weeks since prior betablockers No concurrent photosensitizing drugs No concurrent betablockers No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carboplatin|nan|
|Drug: ifosfamide|nan|
|Procedure: hyperthermia treatment|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progressive disease |  |  | 
| Response rate |  |  | 
| Duration of response |  |  | 
| Survival time |  |  | 
| Effects on the presence of disseminated tumor cells in bone marrow |  |  | 
| Toxicity |  |  | 
| Quality of life |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent ovarian epithelial cancer, recurrent fallopian tube cancer, stage IIIA fallopian tube cancer, stage IIIB fallopian tube cancer, stage IIIC fallopian tube cancer, stage IV fallopian tube cancer, recurrent primary peritoneal cavity cancer, stage IIIA primary peritoneal cavity cancer, stage IIIB primary peritoneal cavity cancer, stage IIIC primary peritoneal cavity cancer, stage IV primary peritoneal cavity cancer, stage IIIA ovarian epithelial cancer, stage IIIB ovarian epithelial cancer, stage IIIC ovarian epithelial cancer, stage IV ovarian epithelial cancer