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

Cervical Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00023660
• Other study ID #: RTOG-C-0128
• Secondary ID: CDR0000068849
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 13, 2001
• Last updated: November 18, 2013
• Start date: August 2001

Study information

• Verified date: November 2013
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 85 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Drug:
• celecoxib

• cisplatin

• fluorouracil

Radiation:
• brachytherapy

• radiation therapy

Locations

Country	Name	City	State
United States	Akron City Hospital - Summa Health System	Akron	Ohio
United States	Akron General Medical Center	Akron	Ohio
United States	New York Methodist Hospital	Brooklyn	New York
United States	State University of New York Health Science Center at Brooklyn	Brooklyn	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Mills-Peninsula Health Services	Burlingame	California
United States	Memorial Hospital Cancer Center	Colorado Springs	Colorado
United States	Mercy Fitzgerald Hospital	Darby	Pennsylvania
United States	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	Sutter Health Western Division Cancer Research Group	Greenbrae	California
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	Baptist Hospital of Miami	Miami	Florida
United States	South Jersey Regional Cancer Center	Millville	New Jersey
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital	Mount Holly	New Jersey
United States	Ball Memorial Hospital Cancer Center	Muncie	Indiana
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha	Omaha	Nebraska
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Foundation for Cancer Research and Education	Phoenix	Arizona
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Regional Radiation Oncology Center at Rome	Rome	Georgia
United States	Dixie Regional Medical Center	Saint George	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Community Medical Center	Toms River	New Jersey
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (9)

Gaffney DK, Winter K, Dicker A, et al.: A phase I-II study of COX-2 inhibitor, celebrex (celecoxib) and chemoradiation in patients with locally advanced cervical cancer: primary endpoint analysis of RTOG 0128. [Abstract] Int J Radiat Oncol Biol Phys 63 (2

Gaffney DK, Winter K, Dicker AP, et al.: Celebrex™ (celecoxib) and chemoradiation in patients with locally advanced cervical cancer. an efficacy report of RTOG 0128. [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-70, S41, 2006.

Gaffney DK, Winter K, Dicker AP, Miller B, Eifel PJ, Ryu J, Avizonis V, Fromm M, Greven K. A Phase II study of acute toxicity for Celebrex (celecoxib) and chemoradiation in patients with locally advanced cervical cancer: primary endpoint analysis of RTOG — View Citation

Gaffney DK, Winter K, Dicker AP, Miller B, Eifel PJ, Ryu J, Avizonis V, Fromm M, Small W, Greven K. Efficacy and patterns of failure for locally advanced cancer of the cervix treated with celebrex (celecoxib) and chemoradiotherapy in RTOG 0128. Int J Radi — View Citation

Gaffney DK, Winter K, Fuhrman C, Flinner R, Greven K, Ryu J, Forbes A, Kerlin K, Nichols RC, Zempolich K. Feasibility of RNA collection for micro-array gene expression analysis in the treatment of cervical carcinoma: a scientific correlate of RTOG C-0128. — View Citation

Viswanathan AN, Moughan J, Small W Jr, Levenback C, Iyer R, Hymes S, Dicker AP, Miller B, Erickson B, Gaffney DK. The quality of cervical cancer brachytherapy implantation and the impact on local recurrence and disease-free survival in radiation therapy oncology group prospective trials 0116 and 0128. Int J Gynecol Cancer. 2012 Jan;22(1):123-31. doi: 10.1097/IGC.0b013e31823ae3c9. — View Citation

Weidhaas JB, Li SX, Winter K, Ryu J, Jhingran A, Miller B, Dicker AP, Gaffney D. Changes in gene expression predicting local control in cervical cancer: results from Radiation Therapy Oncology Group 0128. Clin Cancer Res. 2009 Jun 15;15(12):4199-206. doi: — View Citation

Zempolich K, Fuhrman C, Milash B, Flinner R, Greven K, Ryu J, Forbes A, Kerlin K, Nichols RC, Gaffney DK. Changes in gene expression induced by chemoradiation in advanced cervical carcinoma: a microarray study of RTOG C-0128. Gynecol Oncol. 2008 May;109(2 — View Citation

Zempolich K, Milash B, Fuhrman C, et al.: Changes in gene expression induced by chemoradiation in advanced cervical carcinoma: a microarray study of RTOG C-0128. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A-159, S96, 2005.