• Time to progressive disease [ Designated as safety issue: No ]
  
• Response rate [ Designated as safety issue: No ]
  
• Duration of response [ Designated as safety issue: No ]
  
• Survival time [ Designated as safety issue: No ]
  
• Effects on the presence of disseminated tumor cells in bone marrow [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  
• Quality of life [ Designated as safety issue: No ]
  

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.

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