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

Sponsor:	Ludwig-Maximilians - University of Munich
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00045461

Purpose

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	Intervention	Phase
Fallopian Tube Cancer Ovarian Cancer Peritoneal Cavity Cancer	Drug: carboplatin Drug: ifosfamide Procedure: hyperthermia treatment	Phase II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Fever Ovarian Cancer

Drug Information available for: Carboplatin Ifosfamide

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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 ]

Estimated Enrollment:	241
Study Start Date:	June 2000

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

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00045461

Locations

Germany
Charite University Hospital - Campus Virchow Klinikum	Recruiting
Berlin, Germany, D-13353
Contact: B. Hildebrandt, MD 49-30-450-553-636 bert.hildebrandt@chu-ite.de
Krankenhaus Nordwest	Recruiting
Frankfurt, Germany, D-60488
Contact: Elke Jaeger, MD 49-69-7601-3380
Kreiskrankenhaus Trostberg	Recruiting
Trostberg, Germany, D-83308
Contact: A. Biedermann, MD 0862-11-87-5020
Universitaets - Kinderklinik - Luebeck	Recruiting
Luebeck, Germany, D-23538
Contact: A Bakhshandeh-Bath, MD 0049-451-500-2316 bakhshan@medinf.mu_luebeck.de
University Medical Center Hamburg - Eppendorf	Recruiting
Hamburg, Germany, D-20246
Contact: S. Hegewisch-Becker, MD 49-40-428-033-971 hegewisch@uke.uni-hamburg.de
Hungary
Peterfy Korhaz Szulo-Nobeteg Oztaly	Recruiting
Budapest, Hungary, 1076
Contact: L. Kornya, MD 36-1-322-3450
Netherlands
Academisch Medisch Centrum at University of Amsterdam	Recruiting
Amsterdam, Netherlands, 1105 AZ
Contact: Anneke M. Westermann, MD, PhD 31-20-566-5955 a.m.westermann@amc.uva.nl

Sponsors and Collaborators

Ludwig-Maximilians - University of Munich

Investigators

Study Chair:

Harald Sommer, MD

Ludwig-Maximilians - University of Munich

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000256532, LMU-DOLPHIN-1, EU-20220
Study First Received:	September 6, 2002
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00045461 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

fallopian tube cancer
peritoneal cavity cancer
recurrent ovarian epithelial cancer

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gonadal Disorders
Urogenital Neoplasms
Ovarian Diseases
Genital Diseases, Female
Neoplasms by Site
Therapeutic Uses
Peritoneal Diseases
Alkylating Agents
Endocrine Gland Neoplasms
Ovarian Neoplasms
Digestive System Neoplasms
Genital Neoplasms, Female

Endocrine System Diseases
Carboplatin
Abdominal Neoplasms
Fallopian Tube Neoplasms
Pharmacologic Actions
Adnexal Diseases
Fallopian Tube Diseases
Neoplasms
Ifosfamide
Digestive System Diseases
Peritoneal Neoplasms
Antineoplastic Agents, Alkylating
Isophosphamide mustard

ClinicalTrials.gov processed this record on November 05, 2009