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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Cervical Cancer; Ovarian Cancer; Endometrial Cancer; Vaginal Cancer
• Intervention / Treatment: Drug: capecitabine; Radiation: brachytherapy; Radiation: radiation therapy

Detailed 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.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Charles Kunos, MD, PhD, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

Study record dates

Study Major Dates

• Study Start: April 1, 2005

Study Registration Dates

• First Submitted: July 8, 2005
• First Submitted That Met QC Criteria: July 8, 2005
• First Posted (Estimate): July 11, 2005

Study Record Updates

• Last Update Posted (Estimate): July 8, 2011
• Last Update Submitted That Met QC Criteria: July 7, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: stage III ovarian epithelial cancer; recurrent ovarian epithelial cancer; stage IV endometrial carcinoma; recurrent endometrial carcinoma; stage IIB cervical cancer; stage III cervical cancer; stage IVA cervical cancer; stage IB cervical cancer; stage IIA cervical cancer; ovarian sarcoma; recurrent cervical cancer; ovarian stromal cancer; recurrent ovarian germ cell tumor; stage III ovarian germ cell tumor; stage III endometrial carcinoma; recurrent vaginal cancer; stage III vaginal cancer; stage IVA vaginal cancer; stage I vaginal cancer; stage II vaginal cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Vaginal Diseases; Uterine Cervical Neoplasms; Endometrial Neoplasms; Vaginal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: CASE9804; P30CA043703 (U.S. NIH Grant/Contract); CASE-9804 (Other Identifier: Case Comphrensive Cancer Center); CWRU-010514