Docetaxel and Radiation Therapy in Treating Patients With Stage II, Stage III, or Stage IV Cervical Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Docetaxel may make tumor cells more sensitive to radiation therapy. Giving docetaxel together with radiation therapy may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of docetaxel when given together with radiation therapy and to see how well they work in treating patients with stage II, stage III, or stage IV cervical cancer.

Detailed Description
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OBJECTIVES: Primary Determine the recommended phase II dose (RPTD) of docetaxel when administered with radiotherapy in patients with stage IIB-IVA cervical cancer. (Phase I) Assess the progression-free survival of patients treated with this regimen. (Phase II) Secondary Determine the safety, feasibility, and toxicity of this regimen in these patients. (Phase I) Assess the toxicity of this regimen at the RPTD in these patients. (Phase II) Determine the response in patients treated with this regimen. (Phase II) OUTLINE: This is a phase I, nonrandomized, prospective, dose-escalation study of docetaxel followed by an open-label phase II study. Phase I: Patients receive docetaxel IV over 30 minutes on day 1. Treatment repeats weekly for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo concurrent pelvic external-beam radiotherapy (EBRT) once daily 5 days a week for 5 weeks. Beginning 1-2 weeks after completion of EBRT, patients receive one or two applications of intracavitary low-dose-rate brachytherapy (LDR BT) comprising cesium-137. Cohorts of 3-6 patients receive escalating doses of docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The recommended phase II dose (RPTD) is the dose below the MTD. Phase II: Patients receive docetaxel at the RPTD, EBRT, and LDR BT as in phase I. After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 72 patients will be accrued for this study.

Official Title
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A Phase I/II Study of Docetaxel as a Radiosensitizer for Locally Advanced Cervical Cancer (GIA 13026)

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: docetaxel
* Radiation: cesium Cs 137
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed squamous cell carcinoma of the uterine cervix Locally advanced (stage IIB- IVA) disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 8.0 g/dL WBC ≥ 3,000/mm^3 Creatinine normal Bilirubin normal SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN) if alkaline phosphatase (AP) ≤ ULN OR AP ≤ 4 times ULN if SGOT and SGPT ≤ ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for up to 6 months after completion of study treatment No history of severe allergic reactions to agents containing polysorbate 80 No concurrent uncontrolled illness including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness or social situations that would preclude compliance with study requirements No peripheral neuropathy ≥ grade 2 No HIV positivity PRIOR CONCURRENT THERAPY: More than 4 weeks since prior unrelated therapy and recovered No prior chemotherapy or pelvic radiotherapy No other concurrent investigational agents or anticancer agents or therapies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: docetaxel|nan|
|Radiation: cesium Cs 137|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended phase II dose (Phase I) |  |  | 
| Progression-free survival (Phase II) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response (Phase II) |  |  | 
| Toxicity (Phase II) |  |  | 

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