RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining cisplatin with gemcitabine may make the tumor cells more sensitive to radiation therapy and may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining radiation therapy with cisplatin and gemcitabine in treating patients who have cervical cancer that has not spread beyond the pelvis.

Condition	Treatment or Intervention	Phase
Cervical Cancer	Drug: cisplatin  Drug: gemcitabine  Procedure: brachytherapy  Procedure: chemotherapy  Procedure: radiation therapy  Procedure: radiosensitization	Phase I

Further Study Details: 

OBJECTIVES: Primary

• Determine the toxicity of pelvic radiotherapy and concurrent cisplatin and gemcitabine in patients with cervical carcinoma limited to the pelvis.
• Determine the maximum tolerated dose (MTD) of gemcitabine in combination with cisplatin and pelvic radiotherapy in these patients.

Secondary

• Determine the progression-free and overall survival of patients treated with gemcitabine at the MTD in this regimen.
• Determine the site of recurrence, local versus distant, in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of gemcitabine.

Patients receive gemcitabine IV over 30 minutes and cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36 in the absence of disease progression or unacceptable toxicity. Patients also undergo external whole pelvis radiotherapy once daily on days 1-5, 8-13, 15-20, 22-27, and 29-34. After completion of external beam radiotherapy, patients undergo intracavitary radiotherapy and parametrial radiotherapy. The total elapsed time for completion of all radiotherapy is not more than 8 weeks.

Cohorts of 3-6 patients receive escalating doses of gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 1 of 6 patients experiences dose-limiting toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 1-24 months.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary invasive carcinoma of the uterine cervix
• Previously untreated disease
• Any cell type
• Stage IB_2, IIA, IIB, IIIA, IIIB, or IVA
• Para-aortic lymph nodes negative by radiologic evaluation or by biopsy if CT scan is suspicious for adenopathy
• No known metastases to scalene nodes or other organs outside the radiotherapy field
• Study enrollment within 8 weeks of diagnosis

PATIENT CHARACTERISTICS: Age

• Not specified

Performance status

• GOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times normal
• SGOT no greater than 3 times normal

Renal

• Creatinine less than 2.0 mg/dL
• No renal abnormalities (e.g., pelvic kidney, horseshoe kidney, or renal transplantation) that would require modification of radiotherapy fields
• No ureteral obstruction allowed unless treated with stent or nephrostomy tube

Other

• Not pregnant
• Fertile patients must use effective contraception
• No septicemia or severe infection
• No circumstance that would preclude study completion or follow-up
• No other malignancy within the past 5 years except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior cytotoxic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior pelvic or abdominal radiotherapy

Surgery

• Not specified

Other

• No prior therapy for this malignancy

Arizona
      CCOP - Western Regional, Arizona, Phoenix,  Arizona,  85006-2726,  United States; Recruiting
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States; Recruiting
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States; Recruiting
      CCOP - Central Illinois, Decatur,  Illinois,  62794-9640,  United States; Recruiting
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States; Recruiting
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States; Recruiting
Indiana
      Saint Joseph Regional Medical Center, South Bend,  Indiana,  46617,  United States; Recruiting
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1002,  United States; Recruiting
Michigan
      CCOP - Grand Rapids, Grand Rapids,  Michigan,  49503,  United States; Recruiting
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States; Recruiting
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States; Recruiting
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States; Recruiting
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States; Recruiting
Oregon
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States; Recruiting
Pennsylvania
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States; Recruiting
      UPMC Cancer Center at Magee-Womens Hospital, Pittsburgh,  Pennsylvania,  15213-3180,  United States; Recruiting
Tennessee
      Southeast Gynecologic Oncology Associates, Knoxville,  Tennessee,  37917,  United States; Recruiting
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-2516,  United States; Recruiting
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States; Recruiting

Study chairs or principal investigators

Peter Graham Rose, MD,  Study Chair,  MetroHealth's Cancer Care Center at MetroHealth Medical Center   

Study ID Numbers:  CDR0000327715; GOG-9912; NCT00068549
Record last reviewed:  December 2004
Last Updated:  March 10, 2005
Record first received:  September 10, 2003
ClinicalTrials.gov Identifier:  NCT00068549
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08