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

Case Comprehensive Cancer Center (Case CCC)

Status and phase

Withdrawn

Phase 1

Conditions

Endometrial Cancer

Vaginal Cancer

Ovarian Cancer

Cervical Cancer

Treatments

Radiation: brachytherapy

Drug: capecitabine

Radiation: radiation therapy

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00118300

CASE-9804 (Other Identifier)

CWRU-010514

P30CA043703 (U.S. NIH Grant/Contract)

CASE9804

Details and patient eligibility

About

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.

Full description

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.

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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