Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Radiation Therapy and Either Capecitabine or Fluorouracil With or Without Oxaliplatin Before Surgery in Treating Patients With Resectable Rectal Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over NCI NSABP-R-04 NCT00058474, NSABP-R-04, CALGB-NSABP-R-04

Special Category: CTSU trial, NCI - CMS pilot project trial, NCI Web site featured trial

Objectives

Primary

1. Compare the rate of local-regional relapse in patients with resectable rectal cancer treated with chemoradiotherapy comprising radiation therapy and either capecitabine or fluorouracil with or without oxaliplatin.

Secondary

1. Compare the rate of clinical complete response in patients treated with these regimens.
2. Compare the rate of pathologic complete response in patients treated with these regimens.
3. Determine the increase in the number of patients who are able to undergo sphincter-saving surgery after treatment with these regimens.
4. Correlate genetic patterns and the presence or absence of specific tissue biomarkers with response and prognosis in patients treated with these regimens.
5. Compare preoperative quality of life (QOL) of patients treated with oral capecitabine versus continuous infusion with fluorouracil.
6. Determine the impact of oxaliplatin on neurotoxicity in patients treated with these regimens.
7. Compare the toxic effects of these regimens in these patients.
8. Compare the convenience of care in patients treated with these regimens.
9. Determine the impact of the type of surgical management on QOL at 1 year postoperatively in these patients.

Entry Criteria

Disease Characteristics:

• Diagnosis of adenocarcinoma of the rectum
  • Diagnosis obtained within the past 42 days by a biopsy technique which leaves the major portion of the tumor intact
  • Stage II (T_3-4, N₀ [N₀is defined as all imaged lymph nodes < 1.0 cm]) OR stage III (T_1-4, N_1-2 [with the definition of a clinically positive lymph node being any node ≥ 1.0 cm]
    • Stage of the primary tumor may be determined by ultrasound or MRI (CT scan is acceptable provided there is evidence of T₄ and/or N_1-2 disease



• Tumor palpable by digital rectal exam OR accessible by proctoscope or sigmoidoscope



• Distal border of the tumor must be located < 12 cm from the anal verge



• Tumor amenable to curative resection*

   [Note: *Curative resection can include pelvic exenteration]




• No history of invasive rectal malignancy, regardless of disease-free interval



• No other rectal cancers (i.e., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, or cloacogenic carcinoma)



• No synchronous colon cancer



• No clear indication of involvement of the pelvic side walls by imaging



• No evidence of metastatic disease

Prior/Concurrent Therapy:

Biologic therapy

• No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Radiotherapy

• No prior pelvic radiotherapy

Surgery

• See Disease Characteristics

Other

• No prior therapy for this cancer
• More than 4 weeks since prior participation in any investigational drug study
• No concurrent halogenated antiviral agents (e.g., sorivudine or brivudine)

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

  OR

• Zubrod 0-1

Life expectancy

• At least 5 years (excluding diagnosis of cancer)

Hematopoietic

• Absolute neutrophil count ≥ 1,200/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2 times ULN
• AST ≤ 2 times ULN*
• No hepatic disease that would preclude study treatment or follow-up
• No uncontrolled coagulopathy
• No history of viral hepatitis or other chronic liver disease

 [Note: *If AST is > ULN, serologic testing for Hepatitis B and C must be performed and results must be negative]

Renal

• Creatinine clearance > 50 mL/min
• No renal disease that would preclude study treatment or follow-up

Cardiovascular

• No cardiovascular disease that would preclude study treatment or follow-up
• No New York Heart Association class III or IV heart disease
• No active ischemic heart disease
• No myocardial infarction within the past 6 months
• No symptomatic arrhythmia
• No uncontrolled hypertension

Gastrointestinal

• Able to take oral medications
• No lack of upper gastrointestinal tract integrity or malabsorption syndrome
• No active inflammatory bowel disease (i.e., patients requiring current medical interventions or who are symptomatic)

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• Patients with prior malignancies, including invasive colon cancer, are eligible provided they have been disease-free for ≥ 5 years and are deemed by their physician to be at low risk for recurrence
• No other malignancy within the past 5 years except effectively treated squamous cell or basal cell skin cancer, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum
• No other nonmalignant systemic disease that would preclude study therapy or follow-up
• No known hypersensitivity to fluorouracil, capecitabine, or oxaliplatin
• No clinically significant peripheral neuropathy (i.e., neurosensory or neuromotor toxicity ≥ grade 2)
• No psychiatric or addictive disorders, or other conditions that, in the opinion of the investigator, would preclude study participation

Expected Enrollment

A total of 1,606 patients will be accrued for this study within 4 years.

Outcomes

Loco-regional disease control as assessed by evidence of tumor at 3 years

Clinical complete response as assessed by digital rectal exam and sigmoidoscopy or proctoscopy at time of definitive analysis
Pathologic complete response as assessed by gross and microscopic exam of surgical specimens at time of definitive analysis
Sphincter-saving surgery at time of definitive analysis
Survival as measured by deaths from any cause at time of definitive analysis
Disease-free survival as assessed by recurrence, second primary cancer, or death from any cause at time of definitive analysis
Tissue biomarkers as assessed by analysis of tumor tissue using current biotechnology after definitive analysis
Quality of life as assessed by FACT-C trial outcome index and EORTC CR38 after definitive analysis
Neurotoxicity as assessed by FACT-NTX scale after definitive analysis
Symptoms as assessed by fluoropyrimidine symptom scale adapted from SWOG after definitive analysis
Vitality as assessed by SF-36 vitality scale after definitive analysis
Convenience of care as assessed by NSABP C-06 convenience of care scale adapted from ECOG after definitive analysis

Outline

This is a randomized, multicenter study. Patients are stratified according to participating center, gender, clinical tumor stage (stage II vs stage III), and surgical intent (sphincter saving vs non-sphincter saving). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive fluorouracil IV continuously and undergo radiotherapy once daily 5 days a week for 5-6 weeks.



• Arm II: Patients receive fluorouracil and undergo radiotherapy as in arm I. Patients also receive oxaliplatin IV over 1 hour once weekly for 5 weeks.



• Arm III: Patients receive oral capecitabine twice daily and undergo radiotherapy once daily 5 days a week for 5-6 weeks.



• Arm IV: Patients receive capecitabine and undergo radiotherapy as in arm III. Patients also receive oxaliplatin as in arm II.

Within 6-8 weeks after the completion of chemoradiotherapy, patients with responding or stable disease undergo surgery. Patients with progressive disease are treated at the discretion of the investigator and continue to be followed.

Quality of life is assessed at baseline, at completion of chemoradiotherapy, and at 1 year after surgery.

After completion of study treatment, patients are followed every 6 months for 5 years.

Trial Contact Information

Trial Lead Organizations

National Surgical Adjuvant Breast and Bowel Project

Robert Beart, MD, Protocol chair		Ph: 323-865-3690; 800-865-0102 Email: rbeart@usc.edu

Cancer and Leukemia Group B

David Ryan, MD, Protocol chair		Ph: 617-724-0234; 877-726-5130

U.S.A.
Alabama
	Mobile
	Providence Cancer Center at Providence Hospital
		Paul Schwarzenberger, MD	Ph:  251-435-5892
Arizona
	Scottsdale
	Mayo Clinic Scottsdale
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
Arkansas
	Jonesboro
	Ben E. Owens Cancer Treatment Center at St. Bernard's Medical Center
		Clinical Trials Office - Ben E. Owens Cancer Treatment Center at St. Bernard's Medical Center	Ph:  870-972-4100
California
	Burbank
	Providence Saint Joseph Medical Center - Burbank
		Clinical Trials Office - Providence Saint Joseph Medical Center - Burbank	Ph:  818-847-3220
	Castro Valley
	East Bay Radiation Oncology Center
		James Feusner, MD	Ph:  510-428-3689
	Valley Medical Oncology Consultants - Castro Valley
		James Feusner, MD	Ph:  510-428-3689
	Concord
	Cancer Care Center at John Muir Health - Concord Campus
		Clinical Trials Office - Cancer Care Center at John Muir Health - Concord Campus	Ph:  925-674-2580
	Duarte
	City of Hope Comprehensive Cancer Center
		Clinical Trials Office - City of Hope Comprehensive Cancer Center	Ph:  800-826-4673
			Email: becomingapatient@coh.org
	Fairfield
	North Bay Cancer Center
		Clinical Trials Office - North Bay Cancer Center	Ph:  707-429-6976
	Fremont
	Kaiser Permanente - Fremont
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Valley Medical Oncology
		James Feusner, MD	Ph:  510-428-3689
	Fresno
	Cancer Care Associates
		Charles Kuzma	Ph:  559-326-1222 877-490-4222
	Fullerton
	Virginia K. Crosson Cancer Center at St. Jude Medical Center
		Clinical Trials Office - Virginia K. Crosson Cancer Center	Ph:  714-446-5642
	Glendale
	Glendale Memorial Hospital Comprehensive Cancer Center
		Clinical Trials Office - Glendale Memorial Hospital Comprehensive Cancer Center	Ph:  818-409-7653
	Greenbrae
	California Cancer Care, Incorporated - Greenbrae
		Peter Eisenberg, MD	Ph:  415-925-5000
	Hayward
	Kaiser Permanente Medical Center - Hayward
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	La Jolla
	Rebecca and John Moores UCSD Cancer Center
		Clinical Trials Office - Rebecca and John Moores UCSD Cancer Center	Ph:  858-822-5354
			Email: cancercto@ucsd.edu
	Scripps Cancer Center - San Diego
		William Miller, MD	Ph:  858-554-8832
	Loma Linda
	Loma Linda University Cancer Institute at Loma Linda University Medical Center
		Clinical Trials Office - Loma Linda University Cancer Institute	Ph:  909-558-3375
	Los Angeles
	Cecilia Gonzalez De La Hoya Cancer Center at White Memorial Medical Center
		Lawrence Wagman, MD	Ph:  323-260-5768
	Jonsson Comprehensive Cancer Center at UCLA
		Clinical Trials Office - Jonsson Comprehensive Cancer Center at UCLA	Ph:  888-798-0719
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	Mission Hills
	Providence Holy Cross Cancer Center
		Bahareh Bahadini	Ph:  818-898-4410
	Oakland
	Alta Bates Summit Medical Center - Summit Campus
		Clinical Trials Office - Alta Bates Summit Medical Center - Summit Campus	Ph:  510-204-1414
	Bay Area Breast Surgeons, Incorporated
		James Feusner, MD	Ph:  510-428-3689
	CCOP - Bay Area Tumor Institute
		James Feusner, MD	Ph:  510-428-3689
	Highland General Hospital
		James Feusner, MD	Ph:  510-428-3689
	Kaiser Permanente Medical Center - Oakland
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Larry G Strieff MD Medical Corporation
		James Feusner, MD	Ph:  510-428-3689
	Tom K Lee, Incorporated
		James Feusner, MD	Ph:  510-428-3689
	Pleasanton
	Valley Care Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Valley Medical Oncology Consultants - Pleasanton
		James Feusner, MD	Ph:  510-428-3689
	Pomona
	Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
		Clinical Trials Office - Robert and Beverly Lewis Family Cancer Care Center	Ph:  909-865-9555
	Redding
	North Valley Breast Clinic
		Lawrence Wagman, MD	Ph:  530-243-5551
	Redwood City
	Kaiser Permanente Medical Center - Redwood City
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Richmond
	Kaiser Permanente Medical Center - Richmond
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Roseville
	Kaiser Permanente Medical Center - Roseville
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sacramento
	Kaiser Permanente Medical Center - Sacramento
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South Sacramento Kaiser-Permanente Medical Center
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Salinas
	Salinas Valley Memorial Hospital
		Shehzad Aziz, MD	Ph:  831-755-1701
	San Diego
	Kaiser Permanente Medical Office -Vandever Medical Office
		Jonathan Polikoff, MD	Ph:  619-528-2596
	San Francisco
	Kaiser Permanente Medical Center - San Francisco Geary Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Jose
	Kaiser Permanente Medical Center - Santa Teresa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Pablo
	Doctors Medical Center - San Pablo Campus
		James Feusner, MD	Ph:  510-428-3689
	San Rafael
	Kaiser Foundation Hospital - San Rafael
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sana Rosa
	CCOP - Santa Rosa Memorial Hospital
		Ian Anderson, MD	Ph:  707-521-3830
	Santa Clara
	Kaiser Permanente Medical Center - Santa Clara Kiely Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Santa Rosa
	Kaiser Permanente Medical Center - Santa Rosa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South San Francisco
	Kaiser Permanente Medical Center - South San Francisco
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Stockton
	Kaiser Permanente Medical Facility - Stockton
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Vallejo
	Kaiser Permanente Medical Center - Vallejo
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Walnut Creek
	John Muir/Mt. Diablo Comprehensive Cancer Center
		Clinical Trials Office - John Muir/Mt. Diablo Comprehensive Cancer Center	Ph:  925-941-4246
	Kaiser Permanente Medical Center - Walnut Creek
		Louis Fehrenbacher, MD	Ph:  707-651-2577
Colorado
	Aurora
	Aurora Presbyterian Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	University of Colorado Cancer Center at UC Health Sciences Center
		Clinical Trials Office - University of Colorado Cancer Center	Ph:  720-848-0650
	Boulder
	Boulder Community Hospital
		Clinical Trials Office - Boulder Community Hospital	Ph:  303-938-5253
	Colorado Springs
	Penrose Cancer Center at Penrose Hospital
		Clinical Trials Office - Penrose Cancer Center	Ph:  719-776-5275
	Denver
	CCOP - Colorado Cancer Research Program
		Eduardo Pajon, MD	Ph:  303-777-2663
	Porter Adventist Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	Presbyterian - St. Luke's Medical Center
		Clinical Trials Office - Presbyterian - St. Luke's Medical Center	Ph:  303-839-6000
	Rose Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	St. Anthony Central Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	St. Joseph Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	Englewood
	Swedish Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Fort Collins
	Front Range Cancer Specialists
		Diana Medgyesy, MD	Ph:  970-212-7600
	Poudre Valley Hospital
		Clinical Trials Office - Poudre Valley Hospital	Ph:  970-495-8226
	Grand Junction
	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Greeley
	North Colorado Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Lone Tree
	Sky Ridge Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Longmont
	Hope Cancer Care Center at Longmont United Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	Loveland
	McKee Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Pueblo
	St. Mary - Corwin Regional Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Thornton
	North Suburban Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Wheat Ridge
	Exempla Lutheran Medical Center
		Clinical Trials Office - Exempla Lutheran Medical Center	Ph:  303-403-3605
Connecticut
	Greenwich
	Bendheim Cancer Center at Greenwich Hospital
		Clinical Trials Office - Bendheim Cancer Center	Ph:  203-863-3698
	Norwich
	Eastern Connecticut Hematology and Oncology Associates
		Anca Bulgaru	Ph:  860-886-8362
Delaware
	Lewes
	Tunnell Cancer Center at Beebe Medical Center
		Clinical Trials Office - Tunnell Cancer Center	Ph:  302-645-3171
	Newark
	CCOP - Christiana Care Health Services
		Clinical Trial Office - CCOP - Christiana Care Health Services	Ph:  302-733-6227
District of Columbia
	Washington
	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
		Clinical Trials Office - Lombardi Comprehensive Cancer Center	Ph:  202-444-0381
	Sibley Memorial Hospital
		Frederick Smith, MD	Ph:  301-657-4588
Florida
	Boca Raton
	Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
		Clinical Trials Office - Eugene M. and Christine E. Lynn Cancer Institute	Ph:  561-955-4800
	Fort Lauderdale
	Broward General Medical Center Cancer Center
		Clinical Trials Office - Broward General Medical Center Cancer Center	Ph:  954-355-5346
	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
		Clinical Trials Office - Michael and Dianne Bienes Comprehensive Cancer Center	Ph:  954-776-3239