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

Alternate Title

Bevacizumab and Oxaliplatin Combined With Irinotecan or Leucovorin and Fluorouracil in Treating Patients With Metastatic or Recurrent Colorectal Cancer

Basic Trial Information

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

Objectives

1. Compare the response rate (complete and partial), progression-free survival, and overall survival of patients with previously untreated metastatic or locally recurrent colorectal adenocarcinoma with high vs low thymidylate synthase (TS) expression treated with fluorouracil, leucovorin calcium, oxaliplatin, and bevacizumab or irinotecan, oxaliplatin, and bevacizumab.
2. Compare the toxicity of these regimens in these patients.
3. Correlate gene expression with response rates in patients treated with these regimens.
4. Correlate gene expression with toxicity of these regimens in these patients.
5. Correlate dihydropyrimidine dehydrogenase, thymidine phosphorylase, and mammalian excision repair cross complementary protein expression with antitumor response in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Diagnosis of colorectal adenocarcinoma
  • Metastatic or locally recurrent disease

• Measurable disease

• At least 2 formalin-fixed paraffin embedded core needle biopsies OR fine needle aspirate containing a minimum of 3 clusters of malignant cells and fixed tissue from the previous biopsy
  • If no tissue samples are available the patient must be willing to undergo biopsy of a metastatic site

Prior/Concurrent Therapy:

Biologic therapy

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

Chemotherapy

• No prior chemotherapy for metastatic disease
  • Adjuvant therapy completed at least 12 months before first evidence of metastasis allowed

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• More than 28 days since prior major surgery
• More than 28 days since prior open biopsy

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• PT (INR) ≤ 1.5 unless patient is receiving full-dose anticoagulants AND the following criteria are met:
  • In-range INR (usually between 2 and 3) AND on a stable dose of warfarin or low molecular weight heparin
  • No active bleeding or pathological condition that is associated with a high risk of bleeding
• PTT < 1.5 times upper limit of normal (ULN)
• ALT and AST < 3 times ULN
• Bilirubin ≤ 1.5 times ULN
• No hepatic disease that would preclude study therapy

Renal

• Creatinine ≤ 1.8 mg/dL
• Meets 1 of the following criteria:
  • Protein negative on urine dipstick
  • Urine protein/creatinine ratio < 1.0
  • Less than 2 g protein on 24-hour urine collection
• No renal disease that would preclude study therapy

Cardiovascular

• No arterial thromboembolic events within the past 6 months, including the following:
  • Transient ischemic attack
  • Cerebrovascular accident
  • Unstable angina pectoris
  • Myocardial infarction
• Patients with a history of hypertension must meet the following criteria:
  • Blood pressure < 150/90 mm Hg
  • Stable regimen of anti-hypertensive therapy
• No symptomatic arrhythmia
• No symptomatic congestive heart failure
• No clinically significant peripheral artery disease
• No New York Heart Association class III or IV heart disease
• No other cardiovascular disease that would preclude study therapy

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• Prior non-colorectal malignancies are allowed provided the following criteria are met:
  • No current clinical evidence of persistent or recurrent disease
  • No active therapy for non-colorectal malignancy, including hormonal therapy
• No serious nonhealing wound, ulcer, or bone fracture within the past 28 days
• No significant traumatic injury within the past 28 days
• No neuropathy ≥ grade 2
• No other nonmalignant systemic disease that would preclude study therapy
• No ongoing or active infection

Expected Enrollment

A total of 117-246 patients (40-72 in arm I, 40-72 in arm II, 37-102 in arm III) will be accrued for this study within 14-23 months.

Outcomes

Response rate (complete response [CR] and partial response [PR]) as measured by RECIST

Progression-free survival as measured by time to event at 1 year after closure to accrual
Overall survival as measured by time to event at 1 year after closure to accrual
Toxicity as measured by NCI CTCAE v4.0 at 1 year after closure to accrual

Outline

This is a randomized, multicenter study. Patients are stratified according to thymidylate synthase (TS) expression levels (high vs low or indeterminate). Patients with high TS expression are randomized to 1 of 2 treatment arms (arms I or II). Patients with low or indeterminate TS expression are assigned to arm III.

• Arm I: Patients receive bevacizumab IV over 30-90 minutes followed by oxaliplatin IV over 2 hours and irinotecan IV over 90 minutes on days 1 and 15.

• Arm II: Patients receive bevacizumab and oxaliplatin as in arm I, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on days 1 and 15.

• Arm III: Patients receive bevacizumab, oxaliplatin, leucovorin calcium, and fluorouracil as in arm II.

In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

Patients are followed up every 3 months for 2 years and then every 6 months for 2 years from the date of study registration.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Neal Meropol, MD, Protocol chair (Contact information may not be current)		Ph: 215-728-2450; 888-369-2427
Jean Grem, MD, Protocol co-chair		Ph: 402-559-6210

U.S.A.
Colorado
	Aurora
	Aurora Presbyterian Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	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
	Porter Adventist Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	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
	Englewood
	Swedish Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	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
	Littleton
	Littleton Adventist Hospital
		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
	Parker
	Parker Adventist Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	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
Florida
	Gainesville
	University of Florida Shands Cancer Center
		Clinical Trials Office - University of Florida Shands Cancer Center	Ph:  888-254-7581
Georgia
	Atlanta
	Winship Cancer Institute of Emory University
		Clinical Trials Office - Winship Cancer Institute	Ph:  404-778-1900
	Decatur
	Veterans Affairs Medical Center - Atlanta (Decatur)
		John Kauh	Ph:  404-728-7680
Illinois
	Chicago
	Hematology and Oncology Associates
		Clinical Trails Office - Hematology and Oncology Associates	Ph:  312-695-1301
	Robert H. Lurie Comprehensive Cancer Center at Northwestern University
		Clinical Trials Office - Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Ph:  312-695-1301
			Email: cancer@northwestern.edu
	Saint Joseph Hospital
		Ira Oliff, MD	Ph:  847-673-1999
	Decatur
	Decatur Memorial Hospital Cancer Care Institute
		Clinical Trials Office - Decatur Memorial Hospital Cancer Care Institute	Ph:  217-876-4750
	Kankakee
	Provena St. Mary's Regional Cancer Center - Kankakee
		Mary Mulcahy, MD	Ph:  312-695-6180
	Libertyville
	North Shore Oncology and Hematology Associates, Limited - Libertyville
		Mary Mulcahy, MD	Ph:  312-695-6180
	Niles
	Cancer Care and Hematology Specialists of Chicagoland - Niles
		Mary Mulcahy, MD	Ph:  312-695-6180
	Rockford
	Swedish-American Regional Cancer Center
		Clinical Trials Office - Swedish-American Regional Cancer Center	Ph:  815-489-4413
	Skokie
	Hematology Oncology Associates - Skokie
		Mary Mulcahy, MD	Ph:  312-695-6180
Indiana
	Elkhart
	Elkhart General Hospital
		Bilal Ansari, MD	Ph:  269-983-8260
	Indianapolis
	Indiana University Melvin and Bren Simon Cancer Center
		Clinical Trials Office - Indiana University Cancer Center	Ph:  317-274-2552
	Veterans Affairs Medical Center - Indianapolis
		Patrick Loehrer, MD	Ph:  317-278-7418
	William N. Wishard Memorial Hospital
		Patrick Loehrer, MD	Ph:  317-278-7418
	Kokomo
	Howard Community Hospital
		Bilal Ansari, MD	Ph:  269-983-8260
	La Porte
	Center for Cancer Therapy at LaPorte Hospital and Health Services
		Bilal Ansari, MD	Ph:  269-983-8260
	Lafayette
	Clarian Arnett Cancer Care
		Thomas Jones, MD	Ph:  765-448-7500
	Mishawaka
	Saint Joseph Regional Medical Center
		Bilal Ansari, MD	Ph:  269-983-8260
	South Bend
	CCOP - Northern Indiana CR Consortium
		Bilal Ansari, MD	Ph:  269-983-8260
	Memorial Hospital of South Bend
		Clinical Trials Office - Memorial Hospital of South Bend	Ph:  800-284-7370
Iowa
	Ottumwa
	McCreery Cancer Center at Ottumwa Regional
		Robert Behrens	Ph:  641-684-2946
	Sioux City
	Mercy Medical Center - Sioux City
		Donald Wender, MD, PhD	Ph:  712-252-0088
	Siouxland Hematology-Oncology Associates, LLP
		Donald Wender, MD, PhD	Ph:  712-252-0088
	St. Luke's Regional Medical Center
		Donald Wender, MD, PhD	Ph:  712-252-0088
Michigan
	Saint Joseph
	Lakeside Cancer Specialists, PLLC
		Bilal Ansari, MD	Ph:  269-983-8260
	St. Joseph
	Lakeland Regional Cancer Care Center - St. Joseph
		Bilal Ansari, MD	Ph:  269-983-8260
Minnesota
	Bemidji
	MeritCare Bemidji
		Preston Steen, MD	Ph:  701-234-2397
	Burnsville
	Fairview Ridges Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Coon Rapids
	Mercy and Unity Cancer Center at Mercy Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Edina
	Fairview Southdale Hospital
		Clinical Trials Office - Fairview Southdale Hospital	Ph:  612-625-3650
	Fridley
	Mercy and Unity Cancer Center at Unity Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Hutchinson
	Hutchinson Area Health Care
		Patrick Flynn, MD	Ph:  612-863-8585
	Maplewood
	HealthEast Cancer Care at St. John's Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Minnesota Oncology Hematology, PA - Maplewood
		Patrick Flynn, MD	Ph:  612-863-8585
	Minneapolis
	Hennepin County Medical Center - Minneapolis
		Clinical Trials Office - Hennepin County Medical Center - Minneapolis	Ph:  612-873-5911
	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
		Clinical Trials Office - Virginia Piper Cancer Institute	Ph:  612-863-5654
	Robbinsdale
	Humphrey Cancer Center at North Memorial Outpatient Center
		Clinical Trials Office - Humphrey Cancer Center at North Memorial Outpatient Center	Ph:  763-520-1893
	Saint Louis Park
	CCOP - Metro-Minnesota
		Patrick Flynn, MD	Ph:  612-863-8585
	Park Nicollet Cancer Center
		Patrick Flynn, MD	Ph:  612-863-8585
	Saint Paul
	United Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Shakopee
	St. Francis Cancer Center at St. Francis Medical Center
		Patrick Flynn, MD	Ph:  612-863-8585
	St. Paul
	Regions Hospital Cancer Care Center
		Clinical Trials Office - Regions Hospital Cancer Care Center	Ph:  651-254-1517
	Stillwater
	Lakeview Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Waconia
	Ridgeview Medical Center
		Patrick Flynn, MD	Ph:  612-863-8585
	Willmar
	Willmar Cancer Center at Rice Memorial Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Woodbury
	Minnesota Oncology Hematology, PA - Woodbury
		Patrick Flynn, MD	Ph:  612-863-8585
Nebraska
	Lincoln
	Cancer Resource Center - Lincoln
		Gamini Soori, MD, FACP, FRCP, MBA	Ph:  402-393-3110
	Omaha
	Alegant Health Cancer Center at Bergan Mercy Medical Center
		Clinical Trials Office - Alegant Health Cancer Center at Bergen Mercy Medical Center	Ph:  402-398-6060
	CCOP - Missouri Valley Cancer Consortium
		Gamini Soori, MD, FACP, FRCP, MBA	Ph:  402-393-3110
	Creighton University Medical Center
		Clinical Trials Office - Creighton University Medical Center	Ph:  402-280-4100
	Immanuel Medical Center
		Gamini Soori, MD, FACP, FRCP, MBA	Ph:  402-393-3110
	Lakeside Hospital
		Gamini Soori, MD, FACP, FRCP, MBA	Ph:  402-393-3110
New Jersey
	Marlton
	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
		Clinical Trials Office - Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Ph:  888-847-8823
North Dakota
	Fargo
	CCOP - MeritCare Hospital
		Preston Steen, MD	Ph:  701-234-2397
	Roger Maris Cancer Center at MeritCare Hospital
		Preston Steen, MD	Ph:  701-234-2397
Ohio
	Canton
	Aultman Cancer Center at Aultman Hospital
		Clinical Trials Office - Aultman Cancer Center at Aultman Hospital	Ph:  330-363-6891
	Chillicothe
	Adena Regional Medical Center
		Clinical Trials Office - Adena Regional Medical Center	Ph:  877-779-7585
	Cleveland
	Case Comprehensive Cancer Center
		Clinical Trials Office - Case Comprehensive Cancer Center	Ph:  800-641-2422
	MetroHealth Cancer Care Center at MetroHealth Medical Center
		Bruce Averbook, MD, FACS	Ph:  216-778-4795
	Columbus
	CCOP - Columbus
		J. Philip Kuebler, MD, PhD	Ph:  614-442-3130
	Doctors Hospital at Ohio Health
		Clinical Trials Office - Doctors Hospital at Ohio Health	Ph:  614-566-3275
	Grant Medical Center Cancer Care
		Clinical Trials Office - Grant Medical Center Cancer Care	Ph:  614-566-4475
	Mount Carmel Health - West Hospital
		J. Philip Kuebler, MD, PhD	Ph:  614-442-3130
	Riverside Methodist Hospital Cancer Care
		Clinical Trials Office - Riverside Methodist Hospital Cancer Care	Ph:  614-566-4475
	Delaware
	Grady Memorial Hospital
		J. Philip Kuebler, MD, PhD	Ph:  614-442-3130
	Lancaster
	Fairfield Medical Center
		J. Philip Kuebler, MD, PhD	Ph:  614-442-3130
	Lima
	St. Rita's Medical Center
		Clinical Trials Office - St. Rita's Medical Center	Ph:  419-226-9617
	Marietta
	Strecker Cancer Center at Marietta Memorial Hospital
		J. Philip Kuebler, MD, PhD	Ph:  614-442-3130
	Mount Vernon
	Knox Community Hospital
		J. Philip Kuebler, MD, PhD	Ph:  614-442-3130
	Newark
	Licking Memorial Cancer Care Program at Licking Memorial Hospital
		J. Philip Kuebler, MD, PhD	Ph:  614-442-3130
	Springfield
	Community Hospital of Springfield and Clark County
		J. Philip Kuebler, MD, PhD	Ph:  614-442-3130
	Zanesville
	Genesis - Good Samaritan Hospital
		Clinical Trials Office - Genesis - Good Samaritan Hospital	Ph:  740-454-5232
Oklahoma
	Tulsa
	Natalie Warren Bryant Cancer Center at St. Francis Hospital
		Joseph Lynch, MD	Ph:  918-494-8275
Pennsylvania
	Allentown
	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
		Eliot Friedman, MD	Ph:  610-402-0512
	Bryn Mawr
	Bryn Mawr Hospital
		Clinical Trials Office - Bryn Mawr Hospital	Ph:  610-645-2680
	Paoli
	Cancer Center of Paoli Memorial Hospital
		Clinical Trials Office - Cancer Center of Paoli Memorial Hospital	Ph:  610-648-1637
	Philadelphia
	Fox Chase Cancer Center - Philadelphia
		Clinical Trials Office - Fox Chase Cancer Center - Philadelphia	Ph:  215-728-4790
	Reading
	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
		Clinical Trials Office - McGlinn Family Regional Cancer Center	Ph:  610-988-9323
	Wynnewood
	CCOP - Main Line Health
		Paul Gilman, MD	Ph:  610-645-2000
	Lankenau Cancer Center at Lankenau Hospital
		Paul Gilman, MD	Ph:  610-645-2000
South Dakota
	Sioux Falls
	Avera Cancer Institute
		Addison Tolentino	Ph:  605-322-3000
		Addison Tolentino	Ph:  605-322-3000
Tennessee
	Chattanooga
	Erlanger Cancer Center at Erlanger Hospital - Baroness
		Clinical Trials Office - Erlanger Cancer Center	Ph:  423-778-6947
Texas
	Temple
	CCOP - Scott and White Hospital
		Lucas Wong, MD	Ph:  254-724-1053

Related Information

Featured trial article

Registry Information
Official Title		Phase II Study of Treatment Selection Based Upon Tumor Thymidylate Synthase Expression in Previously Untreated Patients With Metastatic Colorectal Cancer
Trial Start Date		2005-07-14
Trial Completion Date		2012-10-30 (estimated)
Registered in ClinicalTrials.gov		NCT00098787
Date Submitted to PDQ		2004-10-13
Information Last Verified		2012-02-06
NCI Grant/Contract Number		CA21115

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