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

Alternate Title

Oxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over NCI ECOG-E5202 E5202, NCT00217737

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

Objectives

Primary

1. Compare the 3-year disease-free survival of patients with resected stage II colon cancer at high risk for recurrence treated with oxaliplatin, leucovorin calcium, and fluorouracil with vs without bevacizumab.

Secondary

1. Compare the overall survival of patients treated with these regimens.
2. Compare the toxicity profiles of these regimens in these patients.
3. Correlate tumor biologic characteristics with survival of patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the colon
  • Stage II disease (T3-4, N0, M0)
    • At least 8 lymph nodes must have been evaluated



• Meets 1 of the following criteria:
  • High risk for microsatellite instability (MSI) and loss of heterozygosity (LOH) at chromosome 18q
    • Microsatellite stable (MSS) with 18q LOH
    • MSI-low grade (MSI-L) with 18q LOH
  • Low risk for MSI and 18q LOH
    • MSS with retention of 18q alleles
    • MSI-L with retention of 18q alleles
    • MSI-high grade (MSI-H) with retention of 18q alleles
    • MSI-H without retention of 18q alleles
    • MSI-H with 18q status uninformative



• Distal extent of tumor must be ≥ 12 cm from the anal verge by endoscopy or surgical examination
  • If tumor is located beyond sigmoid colon and centimeter distance is unavailable, include anatomic region of the colon (e.g., right colon, transverse colon, hepatic flexure, descending colon, or cecum)



• Has undergone surgical resection of the tumor between the past 28-60 days
  • Must have had a complete resection (R0 resection)



• No history of isolated, distant, or noncontiguous intra-abdominal metastases



• Patients with synchronous tumors or appendiceal tumors are ineligible



• Hereditary non-polyposis colorectal cancer allowed



• Paraffin-embedded tumor specimen (one with normal mucosa and one from the resection tumor) available

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for this cancer

Surgery

• See Disease Characteristics
• More than 28 days since prior major surgery or open biopsy*
• More than 7 days since prior core biopsy or other minor procedure except placement of a vascular access device*

 [Note: *For patients with high-risk disease only]

Other

• No prior systemic therapy for this cancer

 [Note: *For patients with high-risk disease only]

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm³*
• Platelet count ≥ 100,000/mm³*
• No significant bleeding unrelated to tumor within the past 6 months*

 [Note: *For patients with high-risk disease only]

Hepatic

• Bilirubin normal (unless due to Gilbert's disease or similar syndrome)*
• Alkaline phosphatase (AP) < 2.5 times upper limit of normal (ULN)*
• AST < 1.5 times ULN*
• PT INR > 1.5* allowed provided the following criteria are met:
  • Patient is on full-dose anticoagulants
  • INR in range (usually 2-3) on a stable dose of warfarin or low molecular weight heparin
  • No active bleeding or pathological condition associated with a high risk of bleeding unrelated to primary colon tumor
• No systemic hepatic disease*

 [Note: *For patients with high-risk disease only]

Renal

• Creatinine ≤ 1.5 times ULN*
• Urine protein:creatinine ratio < 1.0*

  OR

• Urine protein < 1 gm on 24-hour urine collection*
• No systemic renal disease*

 [Note: *For patients with high-risk disease only]

Cardiovascular

• History of hypertension allowed provided blood pressure < 150/90 mm Hg while on a stable regimen of anti-hypertensive therapy*
• No New York Heart Association class III or IV cardiac disease*
• No symptomatic arrhythmia*
• No history of transient ischemic attack*
• No history of cerebrovascular accident*
• No symptomatic peripheral vascular disease*
• No arterial thromboembolic events within the past 12 months*
• No unstable angina within the past 12 months*
• No myocardial infarction within the past 12 months*
• No other systemic cardiovascular disease*

 [Note: *For patients with high-risk disease only]

Other

• Not pregnant or nursing*
• Negative pregnancy test*
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment*
• No active gastroduodenal ulcer by endoscopy*
• No complete obstruction or perforation of the bowel
• No history of inflammatory bowel disease
• No prior or concurrent malignancy except for nonmelanoma skin cancer, carcinoma in situ of the cervix, breast cancer in situ, treated non-pelvic cancer from which the patient has been disease-free for > 5 years, or history of breast cancer (without evidence of disease) and remain on hormonal therapy for > 5 years
• No other nonmalignant systemic disease that would preclude study compliance*
• No psychiatric or addictive disorder or other condition that would preclude study participation*
• No serious or non-healing wound, skin ulcer, or bone fracture*
• No peripheral neuropathy ≥ grade 2*
• No significant traumatic injury within the past 4 weeks*
• No known allergy to platinum compounds

 [Note: *For patients with high-risk disease only]

Expected Enrollment

A total of 3,610 patients will be accrued for this study within 5.8 years.

Outcomes

Disease-free survival at 3 years

Overall survival
Toxicity
Correlation of tumor biologic characteristics with survival

Outline

This is a randomized study. Patients are stratified according to disease stage (IIA vs IIB) and microsatellite stability (MSS) (stable vs low-grade instability [MSI-L]). Patients with disease that is at high risk for microsatellite instability (MSI) and loss of heterozygosity (LOH) at chromosome 18q are randomized to 1 of 2 treatment arms (arms I and II). Patients with disease that is at low risk for MSI and 18q LOH are assigned to arm III.

• Arm I: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV bolus followed by fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.



• Arm II: Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone for 12 additional courses in the absence of disease progression or unacceptable toxicity.



• Arm III: Patients undergo observation only.

Patients are followed every 3 months for 1-2 years, every 6 months for 3 years, and then annually for up to 10 years from study entry.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Al Benson, MD, FACP, Protocol chair		Ph: 312-695-6180
Peter O'Dwyer, MD, BCh, Protocol co-chair		Ph: 215-662-7606 Email: peter.odwyer@uphs.upenn.edu

U.S.A.
Alabama
	Anniston
	Regional Medical Center
		Stephanie Fussell	Ph:  256-235-5877
	Birmingham
	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
		Clinical Trials Office - Lurleen Wallace Comprehensive Cancer	Ph:  205-934-0309
	Huntsville
	Clearview Cancer Institute
		Clinical Trials Office - Clearview Cancer Institute	Ph:  256-705-4224
	Mobile
	Providence Cancer Center at Providence Hospital
		Paul Schwarzenberger, MD	Ph:  251-544-1013
Alaska
	Anchorage
	Providence Cancer Center
		Clinical Trials Office - Providence Cancer Center	Ph:  907-261-3109
Arizona
	Scottsdale
	Mayo Clinic Scottsdale
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
	Tucson
	Arizona Cancer Center at University of Arizona Health Sciences Center
		Clinical Trials Office - Arizona Cancer Center at University of Arizona Health Sciences Center	Ph:  520-626-9008
Arkansas
	Ft. Smith
	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
		John Wells, MD	Ph:  479-484-4700
California
	Berkeley
	Alta Bates Summit Comprehensive Cancer Center
		Clinical Trials Office - Alta Bates Summit Comprehensive Cancer Center	Ph:  510-204-3428
	Burlingame
	Peninsula Medical Center
		David Irwin, MD	Ph:  510-204-1591
	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
	Fairfield
	North Bay Cancer Center
		Clinical Trials Office - North Bay Cancer Center	Ph:  707-429-6976
	Fremont
	Valley Medical Oncology
		James Feusner, MD	Ph:  510-428-3689
	Washington Township Hospital
		Byron Wilson, MD	Ph:  510-888-0657
	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
	Marin Cancer Institute at Marin General Hospital
		David Irwin, MD	Ph:  510-204-1591
	Sutter Health - Western Division Cancer Research Group
		David Irwin, MD	Ph:  510-204-1591
	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
	Veterans Affairs Medical Center - Loma Linda (Pettis)
		Mark Reeves, MD, PhD	Ph:  909-825-7084ext.6064
	Los Angeles
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	Martinez
	Contra Costa Regional Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Mission Hills
	Providence Holy Cross Cancer Center
		Bahareh Bahadini	Ph:  818-898-4410
	Modesto
	Memorial Medical Center
		Clinical Trials Office - Memorial Medical Center	Ph:  209-572-7116
	Mountain View
	Camino Medical Group - Treatment Center
		Peter Yu, MD	Ph:  408-524-5814
	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
	Larry G Strieff MD Medical Corporation
		James Feusner, MD	Ph:  510-428-3689
	Tom K Lee, Incorporated
		James Feusner, MD	Ph:  510-428-3689
	Orange
	St. Joseph Hospital Regional Cancer Center - Orange
		Timothy Byun	Ph:  714-771-8999
	Palm Springs
	Desert Regional Medical Center Comprehensive Cancer Center
		Clinical Trials Office - Desert Regional Medical Center Comprehensive Cancer Center	Ph:  760-416-4730
	Palo Alto
	Veterans Affairs Medical Center - Palo Alto
		Harlan Pinto, MD	Ph:  650-725-9057
	Pleasanton
	Valley Care Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Valley Medical Oncology Consultants - Pleasanton
		James Feusner, MD	Ph:  510-428-3689
	Rancho Mirage
	Lucy Curci Cancer Center at Eisenhower Memorial Hospital and Medical Center
		Murthy Andavolu	Ph:  760-674-3600
	Sacramento
	University of California Davis Cancer Center
		Clinical Trials Office - University of California Davis Cancer Center	Ph:  916-734-3089
	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:  619-528-5888
	Sharp Memorial Hospital Cancer Center
		Clinical Trials Office - Sharp Memorial Hospital Cancer Center	Ph:  858-939-5015
	San Francisco
	California Pacific Medical Center - California Campus
		David Irwin, MD	Ph:  510-204-1591
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
	San Pablo
	Doctors Medical Center - San Pablo Campus
		James Feusner, MD	Ph:  510-428-3689
	Stanford
	Stanford Cancer Center
		Clinical Trials Office - Stanford Cancer Center	Ph:  650-498-7061
			Email: cctoffice@stanford.edu
	Vallejo
	Sutter Solano Medical Center
		David Irwin, MD	Ph:  510-204-1591
	Walnut Creek
	John Muir/Mt. Diablo Comprehensive Cancer Center
		Clinical Trials Office - John Muir/Mt. Diablo Comprehensive Cancer Center	Ph:  925-941-4246
Colorado
	Aurora
	Aurora Presbyterian Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	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:  303-399-8020ext2261
	Denver Health Medical Center
		Wells Messersmith, MD	Ph:  410-502-6873
	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:  303-399-8020ext2261
	St. Anthony Central Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	St. Joseph Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Veterans Affairs Medical Center - Denver
		Wells Messersmith, MD	Ph:  410-502-6873
	Edwards
	Shaw Regional Cancer Center
		Wells Messersmith, MD	Ph:  410-502-6873
	Englewood
	Swedish Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	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:  303-399-8020ext2261
	Greeley
	North Colorado Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Lone Tree
	Sky Ridge Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Longmont
	Hope Cancer Care Center at Longmont United Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Loveland
	McKee Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Montrose
	Montrose Memorial Hospital Cancer Center
		Clinical Trials Office - Montrose Memorial Hospital Cancer Center	Ph:  670-240-7267
	Pueblo
	St. Mary - Corwin Regional Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Thornton
	North Suburban Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Wheat Ridge
	Exempla Lutheran Medical Center
		Clinical Trials Office - Exempla Lutheran Medical Center	Ph:  303-403-3605
Connecticut
	Bridgeport
	Bridgeport Hospital
		Clinical Trials Office - Bridgeport Hospital	Ph:  203-384-4869
	Norwalk
	Norwalk Hospital
		Richard Frank, MD	Ph:  203-845-2132
	Norwich
	Eastern Connecticut Hematology and Oncology Associates
		Dennis Slater, MD	Ph:  860-886-8362
	Stamford
	Carl and Dorothy Bennett Cancer Center at Stamford Hospital
		Clinical Trials Office - Carl and Dorothy Bennett Cancer Center	Ph:  203-323-8944
Delaware
	Dover
	Kent General Hospital
		Iftekhar Khan, MD	Ph:  302-430-5072
	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