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

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

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.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: fluorouracil; Radiation: radiation therapy; Drug: cisplatin; Radiation: brachytherapy; Drug: celecoxib

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36652-2144
      • Mobile Infirmary Medical Center
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Foundation for Cancer Research and Education
  • California
    • Burlingame, California, United States, 94010
      • Mills-Peninsula Health Services
    • Greenbrae, California, United States, 94904
      • Sutter Health Western Division Cancer Research Group
    • San Francisco, California, United States, 94143-0128
      • UCSF Comprehensive Cancer Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Memorial Hospital Cancer Center
  • Florida
    • Miami, Florida, United States, 33256-2110
      • Baptist Hospital of Miami
  • Georgia
    • Rome, Georgia, United States, 30165
      • Regional Radiation Oncology Center at Rome
  • Illinois
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
  • Indiana
    • Muncie, Indiana, United States, 47303-3499
      • Ball Memorial Hospital Cancer Center
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
  • Nebraska
    • Omaha, Nebraska, United States, 68114-4199
      • Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Southern Nevada Cancer Research Foundation
  • New Jersey
    • Long Branch, New Jersey, United States, 07740-6395
      • Monmouth Medical Center
    • Millville, New Jersey, United States, 08332
      • South Jersey Regional Cancer Center
    • Mount Holly, New Jersey, United States, 08060
      • Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
    • Toms River, New Jersey, United States, 08755
      • Community Medical Center
  • New York
    • Brooklyn, New York, United States, 11203
      • State University of New York Health Science Center at Brooklyn
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-1065
      • Comprehensive Cancer Center at Wake Forest University
  • Ohio
    • Akron, Ohio, United States, 44302
      • Akron General Medical Center
    • Akron, Ohio, United States, 44304
      • Akron City Hospital - Summa Health System
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Darby, Pennsylvania, United States, 19023
      • Mercy Fitzgerald Hospital
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Memorial Hospital
    • Paoli, Pennsylvania, United States, 19301-1792
      • Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19107-5097
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Western Pennsylvania Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Cancer Center at Lankenau Hospital
  • Texas
    • Houston, Texas, United States, 77030-4009
      • University of Texas - MD Anderson Cancer Center
  • Utah
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • CCOP - Marshfield Clinic Research Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

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

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: David K. Gaffney, MD, PhD, University of Utah

Publications and helpful links

General Publications

• 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.
• 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: 10.1158/1078-0432.CCR-08-2257. Epub 2009 Jun 9.
• 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):275-9. doi: 10.1016/j.ygyno.2008.01.027. Epub 2008 Mar 4.
• 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 0128. Int J Radiat Oncol Biol Phys. 2007 Jan 1;67(1):104-9. doi: 10.1016/j.ijrobp.2006.08.002. Epub 2006 Nov 2.
• 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 Radiat Oncol Biol Phys. 2007 Sep 1;69(1):111-7. doi: 10.1016/j.ijrobp.2007.02.050. Epub 2007 May 4.
• 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. Gynecol Oncol. 2005 May;97(2):607-11. doi: 10.1016/j.ygyno.2005.01.014.

Study record dates

Study Major Dates

• Study Start: August 1, 2001
• Primary Completion (Actual): January 1, 2005

Study Registration Dates

• First Submitted: September 13, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): November 19, 2013
• Last Update Submitted That Met QC Criteria: November 18, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: cervical squamous cell carcinoma; stage IIB cervical cancer; stage III cervical cancer; stage IVA cervical cancer; stage IB cervical cancer; stage IIA cervical cancer; cervical adenocarcinoma; cervical adenosquamous cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cyclooxygenase 2 Inhibitors; Fluorouracil; Celecoxib
• Other Study ID Numbers: RTOG-C-0128; CDR0000068849