Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III, Phase II	Treatment	Active	18 to 65	Other	LMU-DOLPHIN-1 EU-20220, NCT00045461

Objectives

1. 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.
2. Compare the response rate, duration of response, and survival time of patients treated with these regimens.
3. Compare the effect on the presence of disseminated tumor cells in bone marrow in patients treated with these regimens.
4. Compare the toxicity of these regimens in these patients.
5. Assess quality of life of patients treated with these regimens.

Entry 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

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

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

Expected Enrollment

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.

Outcomes

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

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.

Trial Contact Information

Trial Lead Organizations

I. Frauenklinik und Hebammenschule der Ludwig-Maximillians Universitaet Muenchen

Harald Sommer, MD, Protocol chair		Ph: 49-89-5160-4313 Email: harald.sommer@med.uni-muenchen.de

Germany
	Berlin
	Charite University Hospital - Campus Virchow Klinikum
		B. Hildebrandt, MD	Ph:  49-30-450-553-636
			Email: bert.hildebrandt@chu-ite.de
	Frankfurt
	Krankenhaus Nordwest
		Elke Jaeger, MD	Ph:  49-69-7601-3380
	Hamburg
	University Medical Center Hamburg - Eppendorf
		S. Hegewisch-Becker, MD	Ph:  49-40-428-033-971
			Email: hegewisch@uke.uni-hamburg.de
	Luebeck
	Universitaets - Kinderklinik - Luebeck
		A Bakhshandeh-Bath, MD	Ph:  0049-451-500-2316
			Email: bakhshan@medinf.mu_luebeck.de
	Trostberg
	Kreiskrankenhaus Trostberg
		A. Biedermann, MD	Ph:  0862-11-87-5020
Hungary
	Budapest
	Peterfy Korhaz Szulo-Nobeteg Oztaly
		L. Kornya, MD	Ph:  36-1-322-3450
Netherlands
	Amsterdam
	Academisch Medisch Centrum at University of Amsterdam
		Anneke Westermann, MD, PhD	Ph:  31-20-566-5955
			Email: a.m.westermann@amc.uva.nl

Registry Information
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
Trial Start Date		2000-06-01
Registered in ClinicalTrials.gov		NCT00045461
Date Submitted to PDQ		2002-07-16
Information Last Verified		2002-10-15

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