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
18 Years
65 Years
Female
Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer
Trial Information
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
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Time to progressive disease
Safety Issue:
No
Principal Investigator
Harald Sommer, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Ludwig-Maximilians - University of Munich
Authority:
Unspecified
Study ID:
CDR0000256532
NCT ID:
NCT00045461
Start Date:
June 2000
Completion Date:
Related Keywords:
- Fallopian Tube Cancer
- Ovarian Cancer
- Primary Peritoneal Cavity Cancer
- 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
- Fever
- Ovarian Neoplasms
- Peritoneal Neoplasms
- Fallopian Tube Neoplasms
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