Radiation Therapy Plus Celecoxib, Fluorouracil, and Cisplatin in Patients With Locally Advanced Cervical Cancer

Study Overview
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Brief Summary
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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. Giving radiation therapy in different ways and combining it with chemotherapy may kill more tumor cells. Celecoxib may slow the growth of cervical cancer by stopping blood flow to the tumor. PURPOSE: Phase I/II trial to study the effectiveness of radiation therapy plus celecoxib, fluorouracil, and cisplatin in treating patients who have locally advanced cervical cancer.

Detailed Description
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OBJECTIVES: Determine treatment-related toxicity rates in patients with locally advanced cervical cancer treated with external beam radiotherapy and brachytherapy concurrently with celecoxib, fluorouracil, and cisplatin. Determine whether this regimen increases locoregional control rates, distant control, disease-free survival, and overall survival in these patients. Determine whether first-failure patterns in patients treated with this regimen are changed compared to historical controls. OUTLINE: This is a multicenter study. Patients undergo external beam pelvic radiotherapy once daily five days a weeks for 5 weeks beginning on day 1. Within 8 weeks, patients undergo low-dose or high-dose brachytherapy. Patients also receive concurrent chemotherapy comprising fluorouracil IV continuously over days 2-5, 23-26, and 44-47 and cisplatin IV over 4 hours on days 1, 22, and 43. Oral celecoxib is administered twice daily beginning on day 1 and continuing for 12 months. 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 83 patients will be accrued for this study within 1.5 years.

Official Title
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A Phase I/II Study Of COX-2 Inhibitor, CELEBREX (CELECOXIB), And Chemoradiation In Patients With Locally Advanced Cervical Cancer

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: celecoxib
* Drug: cisplatin
* Drug: fluorouracil
* Radiation: brachytherapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous, adenocarcinoma, or adenosquamous carcinoma of the cervix Stage IIB-IVA OR Stage IB-IIA with pelvic node metastases and/or tumor size at least 5 cm No small cell, carcinoid, glassy cell, clear cell, or adenoid cystic disease No metastatic disease outside of pelvis No para-aortic disease PATIENT CHARACTERISTICS: Age: 18 to 85 Performance status: Zubrod 0-2 Life expectancy: At least 6 months Hematopoietic: WBC at least 3,000/mm^3 Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL AST or ALT no greater than 2.5 times upper limit of normal (ULN) Renal: Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 50 mL/min Calcium no greater than 1.3 times ULN Cardiovascular: No severe heart disease Other: Not pregnant or nursing Negative pregnancy test HIV negative No prior allergy to sulfonamides or non-steroidal anti-inflammatory drugs (NSAIDs) No prior hypersensitivity to celecoxib or any component of its formulation No medical or psychiatric illness that would preclude study No active gastrointestinal (GI) ulcer, GI bleeding, or inflammatory bowel disease No other prior malignancy within the past 5 years except cutaneous basal cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy: No recent prior celecoxib or other cyclo-oxygenase-2 inhibitor Chemotherapy: No prior systemic chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to pelvis except transvaginal radiotherapy to control bleeding Surgery: No prior surgery for cervical cancer except biopsy Other: No concurrent phenytoin or lithium No other concurrent NSAIDs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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

| Intervention/Treatment |
| --- |
|Drug: celecoxib|nan|
|Drug: cisplatin|nan|
|Drug: fluorouracil|nan|
|Radiation: brachytherapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

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