Clinical trial NCT00023660: Radiation Therapy Plus Celecoxib, Fluorouracil, and Cisplatin in Patients With Locally Advanced Cervical Cancer
Official title: A Phase I/II Study Of COX-2 Inhibitor, CELEBREX (CELECOXIB), And Chemoradiation In Patients With Locally Advanced Cervical Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cervical Cancer
Keywords: stage III cervical cancer
stage IB cervical cancer
stage IIB cervical cancer
stage IIA cervical cancer
stage IVA cervical cancer
cervical squamous cell carcinoma
cervical adenocarcinoma
cervical adenosquamous cell carcinoma
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 84
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Phoenix
country: United States
facility: Foundation for Cancer Research and Education
state: Arizona
city: Burlingame
country: United States
facility: Mills-Peninsula Health Services
state: California
city: Greenbrae
country: United States
facility: Sutter Health Western Division Cancer Research Group
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: Colorado Springs
country: United States
facility: Memorial Hospital Cancer Center
state: Colorado
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Rome
country: United States
facility: Regional Radiation Oncology Center at Rome
state: Georgia
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Muncie
country: United States
facility: Ball Memorial Hospital Cancer Center
state: Indiana
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Omaha
country: United States
facility: Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Millville
country: United States
facility: South Jersey Regional Cancer Center
state: New Jersey
city: Mount Holly
country: United States
facility: Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Toms River
country: United States
facility: Community Medical Center
state: New Jersey
city: Brooklyn
country: United States
facility: State University of New York Health Science Center at Brooklyn
state: New York
city: Brooklyn
country: United States
facility: New York Methodist Hospital
state: New York
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Akron
country: United States
facility: Akron General Medical Center
state: Ohio
city: Akron
country: United States
facility: Akron City Hospital - Summa Health System
state: Ohio
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Darby
country: United States
facility: Mercy Fitzgerald Hospital
state: Pennsylvania
city: Drexel Hill
country: United States
facility: Delaware County Memorial Hospital
state: Pennsylvania
city: Paoli
country: United States
facility: Paoli Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Saint George
country: United States
facility: Dixie Regional Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Marshfield
country: United States
facility: CCOP - Marshfield Clinic Research Foundation
state: Wisconsin
Study officials:
affiliation: University of Utah
name: David K. Gaffney, MD, PhD
role: STUDY_CHAIR
References:
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.
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: 10.1158/1078-0432.CCR-08-2257. Epub 2009 Jun 9.
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):275-9. doi: 10.1016/j.ygyno.2008.01.027. Epub 2008 Mar 4.
citation: 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.
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 Radiat Oncol Biol Phys. 2007 Sep 1;69(1):111-7. doi: 10.1016/j.ijrobp.2007.02.050. Epub 2007 May 4.
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. Gynecol Oncol. 2005 May;97(2):607-11. doi: 10.1016/j.ygyno.2005.01.014.