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 radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining radiation therapy with chemotherapy in treating patients who have locally advanced cervical cancer.

Condition	Treatment or Intervention	Phase
cervical adenocarcinoma Cervical Cancer cervical squamous cell carcinoma	Drug: cisplatin  Drug: topotecan  Procedure: chemotherapy  Procedure: radiation therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the toxicity of pelvic or extended field radiotherapy, cisplatin, and topotecan in patients with locally advanced cervical cancer.
• Determine the maximum tolerated dose (MTD) of topotecan when administered in this regimen in this patient population.
• Determine the progression-free survival of patients treated at the MTD.
• Determine the overall survival of patients treated at the MTD.
• Determine the site of recurrence (local vs distant) in patients treated with this regimen.

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

Patients undergo radiotherapy to the pelvic or pelvic and para-aortic fields 5 days a week for 5-6 weeks. Patients receive cisplatin IV and oral topotecan once weekly for a total of 6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of topotecan 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. Once the MTD is determined, an additional cohort of 20 patients receives treatment as above at the MTD.

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

PROJECTED ACCRUAL: A total of 20-30 patients will be accrued for this study within 4-6 years.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary invasive carcinoma of the uterine cervix
• Stage IB-IVA disease
• Any cell type
• Histologically or cytologically confirmed metastasis to the para-aortic lymph nodes or candidates for pelvic and para-aortic field radiation (with a negative CT scan of the chest)
• No known metastasis to scalene nodes or organs outside the radiation field
• No known intraperitoneal metastases
• Must enroll within 8 weeks of diagnosis

PATIENT CHARACTERISTICS: Age

• Not specified

Performance status

• GOG 0-2

Life expectancy

• Not specified

Hematopoietic

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

Hepatic

• Bilirubin ≤ 1.5 times normal
• SGOT ≤ 3 times normal

Renal

• Creatinine < 2.0 mg/dL
• Prior ureteral obstruction allowed provided stent or nephrostomy tube has been placed
• No renal abnormalities, such as pelvic kidney, horseshoe kidney, or prior renal transplantation that would require modification of radiation fields

Other

• Not pregnant
• No other malignancy within the past 5 years except nonmelanoma skin cancer
• No septicemia or severe infection
• No other medical or psychiatric condition that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for any prior malignancy
• No prior cytotoxic chemotherapy for this malignancy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for any prior malignancy
• No prior pelvic or abdominal radiotherapy for this malignancy

Surgery

• See Patient Characteristics- Renal

Other

• No prior therapy for this malignancy

Study chairs or principal investigators

Peter Graham Rose, MD,  Study Chair,  Cleveland Clinic Cancer Center   

Study ID Numbers:  CDR0000270680; GOG-9913; NCT00054444
Record last reviewed:  December 2004
Last Updated:  January 6, 2005
Record first received:  February 5, 2003
ClinicalTrials.gov Identifier:  NCT00054444
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08