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

Sponsor

Ludwig-Maximilians - University of Munich (Other)

Overall Status

Unknown status

CT.gov ID

NCT00045461

Collaborator

(none)

241

Enrollment

Locations

34.4

Patients Per Site

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer Ovarian Cancer Primary Peritoneal Cavity Cancer	Drug: carboplatin Drug: ifosfamide Procedure: hyperthermia treatment	Phase 2/Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

241 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2000

Outcome Measures

Primary Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Charite University Hospital - Campus Virchow Klinikum	Berlin	Germany	D-13353
2	Krankenhaus Nordwest	Frankfurt	Germany	D-60488
3	University Medical Center Hamburg - Eppendorf	Hamburg	Germany	D-20246
4	Universitaets - Kinderklinik - Luebeck	Luebeck	Germany	D-23538
5	Kreiskrankenhaus Trostberg	Trostberg	Germany	D-83308
6	Peterfy Korhaz Szulo-Nobeteg Oztaly	Budapest	Hungary	1076
7	Academisch Medisch Centrum at University of Amsterdam	Amsterdam	Netherlands	1105 AZ