Radiation Therapy, Paclitaxel, and Cisplatin in Treating Patients With Cancer of the Cervix

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Paclitaxel and cisplatin may increase the effectiveness of radiation therapy by making the tumor cells more sensitive to the radiation. 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: This phase I/II trial is studying the side effects and best dose of paclitaxel when given with radiation therapy and cisplatin and to see how well they work in treating patients with cancer of the cervix that has spread to the lymph nodes in the pelvis and abdomen.

Detailed Description
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OBJECTIVES: Determine the toxicity of extended field radiotherapy with concurrent paclitaxel and cisplatin chemotherapy (as radiation sensitization) in patients with previously untreated carcinoma of the cervix metastatic to the para-aortic lymph nodes. Determine the maximum tolerated dose of paclitaxel when combined with cisplatin plus extended field radiotherapy in this patient population. Determine the effect of this treatment regimen on progression-free survival, overall survival, and site of recurrence (local vs distant) in these patients. OUTLINE: This is a multicenter, dose-escalation study of paclitaxel. Patients receive external beam radiotherapy (RT) to the para-aortic nodes and the pelvis daily for 5 weeks; RT must be completed within 8 weeks of its initiation. During or after external beam RT, intracavitary radiation is administered 1-5 times. Concurrently with external beam RT, patients receive paclitaxel IV over 1 hour followed immediately by cisplatin IV on days 1, 8, 15, 22, 29, and 36. Cohorts of 3-6 patients receive escalating doses of paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter or until the time of recurrence or death. PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 4 years.

Official Title
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A Phase I Study of Extended Field Radiation Therapy With Concomitant Paclitaxel and Cisplatin Chemotherapy in Patients Cervical Carcinoma Metastatic to the Para-Aortic Lymph Nodes

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: paclitaxel
* Radiation: brachytherapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven previously untreated invasive carcinoma of the uterine cervix Squamous cell carcinoma Adenosquamous carcinoma Adenocarcinoma TNM classification stage IIIB or IVA (FIGO classification stage IB, IIA, IIB, IIIA, IIIB, or IVA) Cytologically or histologically proven metastases to the para-aortic lymph nodes No more than 8 weeks since diagnosis No metastases to scalene nodes, intraperitoneal metastases, or metastases to other organs outside the radiation field at the time of original clinical and surgical staging Negative CT scan of the chest Patients with ureteral obstruction must be treated with stent or nephrostomy tube PATIENT CHARACTERISTICS: Age: 18 and over Performance status: GOG 0-2 Life expectancy: At least 6 months 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) requiring modification of radiation fields Other: Not pregnant No septicemia or severe infection No other invasive malignancy within the past 3 years except nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior cytotoxic chemotherapy for this or other malignancy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy for this or other malignancy No prior radiotherapy to pelvis or abdomen Surgery: Not specified Other: No other prior therapy for this malignancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Radiation therapy plus concurrent weekly chemotherapy<br> | Drug: cisplatin<br> <br> Drug: paclitaxel<br> <br> Radiation: brachytherapy<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment |  | up to 21 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival at 2 Years | Product-limit estimate of the probability of being alive and progression-free at 24 months based on those 20 patients who were treated at the study recommended dose level (RDL) is 0.65, 95% confidence interval (0.44-0.86). Progression is defined as a 50% or greater increase in the product from any lesion documented within eight weeks for study entry or the appearance of any new lesion within eight weeks of entry into study. | 2 years | 
| Overall Survival at 2 Years | Product-limit estimate of the probability of being alive at 24 months based on those 20 patients who were treated at the study recommended dose-level is 0.80, 95 % confidence interval (0.62-0.97) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III cervical cancer, stage IVA cervical cancer, cervical squamous cell carcinoma, cervical adenocarcinoma, cervical adenosquamous cell carcinoma