Clinical trial NCT00045461: Combination Chemotherapy With or Without Whole-Body Hyperthermia in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cancer
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cavity Cancer
Keywords: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 241
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Time to progressive disease
measure: Response rate
measure: Duration of response
measure: Survival time
measure: Effects on the presence of disseminated tumor cells in bone marrow
measure: Toxicity
measure: Quality of life
Secondary outcomes:
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite University Hospital - Campus Virchow Klinikum
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest
city: Hamburg
country: Germany
facility: University Medical Center Hamburg - Eppendorf
city: Luebeck
country: Germany
facility: Universitaets - Kinderklinik - Luebeck
city: Trostberg
country: Germany
facility: Kreiskrankenhaus Trostberg
city: Budapest
country: Hungary
facility: Peterfy Korhaz Szulo-Nobeteg Oztaly
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
Study officials:
affiliation: Ludwig-Maximilians - University of Munich
name: Harald Sommer, MD
role: STUDY_CHAIR
References: