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

Radiation Therapy Oncology Group

Status and phase: Completed; Phase 2; Phase 1

Conditions: Cervical Cancer

Treatments: Radiation: brachytherapy; Drug: celecoxib; Radiation: radiation therapy; Drug: cisplatin; Drug: fluorouracil

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00023660

CDR0000068849

RTOG-C-0128

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 84 patients

Sex: Female

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)