Capecitabine and Radiation Therapy in Treating Patients With Locally Advanced Cervical Cancer or Other Pelvic Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as capecitabine, 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. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Giving chemotherapy together with radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of capecitabine when given together with radiation therapy in treating patients with locally advanced cervical cancer or other pelvic cancer.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose and dose-limiting toxicity of capecitabine when given in combination with pelvic external beam radiotherapy and intracavitary brachytherapy in patients with primary or recurrent locally advanced cervical cancer or other pelvic malignancy. Secondary Determine the clinical anti-tumor response in patients treated with this regimen. Determine adverse clinical sequelae in patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of capecitabine. Patients undergo external beam radiotherapy to the whole pelvis once daily 5 days a week in weeks 1-5 and receive 1 or 2 applications of low-dose rate intracavitary brachytherapy in weeks 7-8 OR 5 applications of high-dose rate (HDR)* intracavitary brachytherapy once weekly in weeks 4-8. Patients also receive oral capecitabine twice daily 7 days a week in weeks 1-5 and 7-8. Courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. NOTE: *No external beam radiotherapy is administered on the day of HDR brachytherapy. If the majority of external beam radiotherapy has been administered, HDR brachytherapy may be administered in 2 applications per week (separated by at least 72 hours) in order to complete all treatment by week 8. Cohorts of 3-6 patients receive escalating doses of capecitabine 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. A minimum of 6 patients are treated at the MTD. After completion of study treatment, patients are followed at 1 month, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years. PROJECTED ACCRUAL: Approximately 4-24 patients will be accrued for this study within 2-12 months.

Official Title
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Phase I Study of Capecitabine (Xeloda) and Radiation Therapy in Patients With Locally Advanced Cervical and Pelvic Malignancies

Conditions
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Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Vaginal Cancer

Intervention / Treatment
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* Drug: capecitabine
* Radiation: brachytherapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed cervical cancer or other pelvic malignancy, including vaginal, endometrial, or ovarian cancer Primary or recurrent disease Locally advanced disease, defined as the following: Stage IB2-IVA (for cervical or vaginal cancer) Any non-extra pelvic metastatic stage (for endometrial or ovarian cancer) Not amenable to curative surgical resection alone Bidimensionally measurable or clinically evaluable disease Refused or ineligible for weekly IV cisplatin chemotherapy due to renal insufficiency, prior platinum adverse sensitivity, pre-existing neuropathy, or concurrent co-morbid illness No histologically confirmed or clinically suspicious (≥ 1 cm) para-aortic lymphadenopathy No brain metastases or primary brain tumors PATIENT CHARACTERISTICS: Age 18 and over (80 and under for second and third dose-escalation levels) Performance status GOG 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Absolute granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10.0 g/dL Hepatic Bilirubin ≤ 1.5 mg/dL AST and ALT < 2 times upper limit of normal Renal See Disease Characteristics Creatinine normal OR Creatinine clearance ≥ 30 mL/min* No proteinuria or clinically significant impaired renal function NOTE: *Creatine clearance testing required in patients > 60 years of age Cardiovascular No symptomatic New York Heart Association class III or IV congestive heart failure No unstable angina pectoris No cardiac arrhythmia No uncontrolled hypertension Gastrointestinal Able to swallow oral medication No bowel obstruction No malabsorption illness Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known hypersensitivity to capecitabine or fluorouracil No ongoing or active infection No other uncontrolled illness No psychiatric illness or social situation that would preclude study compliance No other active invasive malignancy Prior malignancy in remission for ≥ 6 months that is not currently being treated allowed PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Recovered from prior chemotherapy At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) Prior chemotherapy for a non-gynecologic malignancy or in the adjuvant setting allowed No prior capecitabine Endocrine therapy Prior adjuvant hormonal therapy allowed Radiotherapy Recovered from prior radiotherapy At least 4 weeks since prior radiotherapy Prior radiotherapy for a non-gynecologic malignancy allowed No prior low abdominal or pelvic radiotherapy Surgery Not specified Other At least 3 weeks since prior investigational anticancer agents and recovered No prior anticancer treatment that contraindicates study therapy

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

| Intervention/Treatment |
| --- |
|Drug: capecitabine|Patients also receive oral capecitabine twice daily 7 days a week in weeks 1-5 and 7-8. Courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.|
|Radiation: brachytherapy|1 or 2 applications of low-dose rate intracavitary brachytherapy in weeks 7-8 OR 5 applications of high-dose rate (HDR)* intracavitary brachytherapy once weekly in weeks 4-8.|
|Radiation: radiation therapy|Patients undergo external beam radiotherapy to the whole pelvis once daily 5 days a week in weeks 1-5.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  | weekly | 
| Disease response measured prior to brachytherapy and at 1 month after completion of study treatment |  | 1 month after completion of study treatment | 
| Toxicity as measured by CTC v 3.0 weekly |  | weekly | 

 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, recurrent cervical cancer, stage III endometrial carcinoma, recurrent endometrial carcinoma, stage III ovarian epithelial cancer, recurrent ovarian epithelial cancer, stage III ovarian germ cell tumor, recurrent ovarian germ cell tumor, stage III vaginal cancer, stage IVA vaginal cancer, recurrent vaginal cancer, ovarian sarcoma, ovarian stromal cancer, stage IV endometrial carcinoma, stage IB cervical cancer, stage IIA cervical cancer, stage IIB cervical cancer, stage II vaginal cancer, stage I vaginal cancer