Radiation Therapy and Cisplatin With or Without Amifostine in Treating Patients With Stage IIIB or Stage IVA Cancer of the Cervix

Condition(s) targeted: Cervical Cancer; Radiation Toxicity

Intervention: amifostine trihydrate (Drug); cisplatin (Drug); brachytherapy (Procedure); radiation therapy (Procedure)

Phase: Phase 1/Phase 2

Status: Active, not recruiting

Sponsored by: Radiation Therapy Oncology Group

Official(s) and/or principal investigator(s):
William Small, MD, Study Chair, Affiliation: Robert H. Lurie Cancer Center

RATIONALE: Drugs used in chemotherapy, such as cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Drugs such as amifostine may protect normal cells from the side effects of radiation therapy.

PURPOSE: Phase I/II trial to study the effectiveness of combining cisplatin and radiation therapy with or without amifostine in treating patients who have stage IIIB or stage IVA cancer of the cervix.

Official title: A Two Part Phase I/II Study Of Extended Field External Irradiation And Intracavitary Brachytherapy Combined With Chemotherapy (Weekly Cisplatin-Arm1) And Amifostine (Arm 2) In Carcinoma Of The Cervix With Positive Para-Aortic Or High Common Iliac Lymph Nodes

Study design: Treatment, Open Label

Primary outcome:

Feasibility and tolerability

Toxicity

Secondary outcome:

Pelvic tumor control

Distant metastases

Detailed description: OBJECTIVES:

- Determine the feasibility and tolerability of external beam radiotherapy, brachytherapy,

and cisplatin in patients with para-aortic or high common iliac lymph node-positive carcinoma of the uterine cervix.

- Determine the feasibility and tolerability of this regimen with the addition of

amifostine in these patients.

- Determine the efficacy of these 2 regimens, in terms of improving pelvic and para-aortic

tumor control and distant metastases, in these patients.

OUTLINE:

- Phase I: Patients undergo external beam radiotherapy to the pelvis and para-aortic

region 5 days a week for 5 weeks. Patients also undergo either intracavitary low-dose rate (LDR) brachytherapy in 2 applications beginning within 2 weeks after completion of external beam radiotherapy at 2-3 week intervals or 6 fractions of high-dose rate intracavitary brachytherapy over 8 weeks beginning as early as week 2 of external beam radiotherapy. Patients also receive cisplatin IV over 1 hour weekly for 6 weeks concurrently with external beam radiotherapy and once with LDR brachytherapy. Phase II proceeds only if toxicity in phase I is within expected parameters.

- Phase II: Patients receive external beam radiotherapy, brachytherapy, and cisplatin as

in phase I. Patients also receive amifostine subcutaneously daily just before external beam radiotherapy and cisplatin. Treatment continues for up to 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40-66 patients (27 for phase I and 13-39 for phase II) will be accrued for this study within 12-30 months.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically proven, locally advanced carcinoma of the uterine cervix

- TNM classification stage IIIB or IVA

- Disease metastatic to para-aortic or high common iliac lymph nodes

- Prior complete surgical resection of involved lymph nodes or gross residual

tumor involvement of a lymph node allowed

- The following cellular types are eligible:

- Squamous cell carcinoma

- Adenocarcinoma

- Adenosquamous carcinoma

- The following cellular types are ineligible:

- Small cell carcinoma

- Carcinoid tumor

- Glassy cell carcinoma

- Clear cell carcinoma

- Cystadenocarcinoma

- No metastatic disease outside of the pelvis (except to the para-aortic nodes)

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Zubrod 0-1

Life expectancy

- At least 6 months

Hematopoietic

- WBC at least 3,000/mm^3

- Platelet count at least 100,000/mm^3

Hepatic

- Bilirubin no greater than 1. 5 mg/dL

- ALT no greater than 2 times normal

Renal

- Creatinine no greater than 1. 5 mg/dL (urinary diversion allowed)

- Corrected calcium normal

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No concurrent significant medical condition that would preclude study participation

- No insulin-dependent diabetes

- No other malignancy within the past 3 years except cutaneous basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- No prior systemic chemotherapy

Endocrine therapy

- Not specified

Radiotherapy

- No prior pelvic irradiation except transvaginal radiotherapy to control bleeding

Surgery

- See Disease Characteristics

- No prior tumor-directed surgery except lymph node biopsy/staging

Baptist Cancer Institute - Jacksonville, Jacksonville, Florida 32207, United States

Baptist Medical Center South, Jascksonville, Florida 32258, United States

Flagler Cancer Center, Saint Augustine, Florida 32086, United States

Florida Cancer Center - Palatka, Palatka, Florida 32177, United States

Florida Oncology Associates at Southside Cancer Center, Jacksonville, Florida 32207, United States

Florida Oncology Associates, Orange Park, Florida 32073, United States

Integrated Community Oncology Network, Jacksonville Beach, Florida 32250, United States

Borgess Medical Center, Kalamazooaa, Michigan 49001, United States

Bronson Methodist Hospital, Kalamazoo, Michigan 49007, United States

West Michigan Cancer Center, Kalamazoo, Michigan 49007-3731, United States

CCOP - Nevada Cancer Research Foundation, Las Vegas, Nevada 89106, United States

University Medical Center of Southern Nevada, Las Vegas, Nevada 89102, United States

Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton, Marlton, New Jersey 08053, United States

Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare, Vineland, New Jersey 08360, United States

Akron City Hospital, Akron, Ohio 44309-2090, United States

Cancer Treatment Center, Wooster, Ohio 44691, United States

Mercy Cancer Institute at Mercy Hospital, Pittsburgh, Pennsylvania 15219, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: August 2001
Last updated: May 23, 2008