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

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active 18 and over NCI ECOG-E4203 E4203, NCT00098787

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 1 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 v3.0 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 for 4 years from the date of study registration.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Neal Jay Meropol, MD, Protocol chair		Ph: 215-728-2450; 888-369-2427
Jean Grem, MD, Protocol co-chair		Ph: 402-559-6210

U.S.A.
Illinois
	Aurora
	Rush-Copley Cancer Care Center
		Kendrith Rowland, MD	Ph:  217-383-3010
	Chicago
	Rush University Medical Center
		Clinical Trials Office - Rush University Medical Center	Ph:  312-942-5498
			Email: clinical_trials@rush.edu
	Joliet
	Joliet Oncology-Hematology Associates, Limited - West
		Kendrith Rowland, MD	Ph:  217-383-3010
	Rockford
	Swedish-American Regional Cancer Center
		Clinical Trials Office - Swedish-American Regional Cancer Center	Ph:  815-489-4413
	Springfield
	Regional Cancer Center at Memorial Medical Center
		Clinical Trials Office - Regional Cancer Center at Memorial Medical Center	Ph:  217-788-4233
	Urbana
	Carle Cancer Center at Carle Foundation Hospital
		Clinical Trials Office - Carle Cancer Center	Ph:  800-446-5532
	CCOP - Carle Cancer Center
		Clinical Trials Office - CCOP - Carle Cancer Center	Ph:  800-446-5532
Indiana
	Elkhart
	Elkhart General Hospital
		Bilal Ansari, MD	Ph:  574-237-1328
	Kokomo
	Howard Community Hospital
		Bilal Ansari, MD	Ph:  574-237-1328
	La Porte
	Center for Cancer Therapy at LaPorte Hospital and Health Services
		Bilal Ansari, MD	Ph:  574-237-1328
	Michigan City
	Saint Anthony Memorial Health Centers
		Kendrith Rowland, MD	Ph:  217-383-3010
	South Bend
	CCOP - Northern Indiana CR Consortium
		Bilal Ansari, MD	Ph:  574-237-1328
	Memorial Hospital of South Bend
		Clinical Trials Office - Memorial Hospital of South Bend	Ph:  800-284-7370
	Saint Joseph Regional Medical Center
		Bilal Ansari, MD	Ph:  574-237-1328
Michigan
	Kalamazoo
	Bronson Methodist Hospital
		Raymond Lord, MD	Ph:  269-373-7488
	West Michigan Cancer Center
		Clinical Trials Office - West Michigan Cancer Center	Ph:  269-373-7458
	St. Joseph
	Lakeland Regional Cancer Care Center - St. Joseph
		Bilal Ansari, MD	Ph:  574-237-1328
Minnesota
	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
	Maplewood
	Minnesota Oncology Hematology, PA - Maplewood
		Patrick Flynn, MD	Ph:  612-863-8585
	Minneapolis
	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
		Clinical Trials Office - Virginia Piper Cancer Institute	Ph:  612-863-5654
	Robbinsdale
	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
		Clinical Trials Office - Hubert H. 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
	Waconia
	Ridgeview Medical Center
		Patrick Flynn, MD	Ph:  612-863-8585
	Woodbury
	Minnesota Oncology Hematology, PA - Woodbury
		Patrick Flynn, MD	Ph:  612-863-8585
Nebraska
	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
New Jersey
	Hamilton
	Cancer Institute of New Jersey at Hamilton
		Clinical Trials Office - Cancer Institute of New Jersey at Hamilton	Ph:  609-631-6946
	New Brunswick
	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
		Clinical Trials Office - Cancer Institute of New Jersey	Ph:  732-235-8675
Ohio
	Bellefontaine
	Mary Rutan Hospital
		J. Philip Kuebler, MD, PhD	Ph:  614-488-2118
	Chillicothe
	Adena Regional Medical Center
		Clinical Trials Office - Adena Regional Medical Center	Ph:  877-779-7585
	Columbus
	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:  614-488-2118
	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:  614-488-2118
	Lancaster
	Fairfield Medical Center
		J. Philip Kuebler, MD, PhD	Ph:  614-488-2118
	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:  614-488-2118
	Newark
	Licking Memorial Cancer Care Program at Licking Memorial Hospital
		J. Philip Kuebler, MD, PhD	Ph:  614-488-2118
	Springfield
	Community Hospital of Springfield and Clark County
		J. Philip Kuebler, MD, PhD	Ph:  614-488-2118
	Mercy Medical Center
		J. Philip Kuebler, MD, PhD	Ph:  614-488-2118
	Westerville
	Mount Carmel St. Ann's Cancer Center
		J. Philip Kuebler, MD, PhD	Ph:  614-488-2118
	Zanesville
	Genesis - Good Samaritan Hospital
		Clinical Trials Office - Genesis - Good Samaritan Hospital	Ph:  740-454-5232
Pennsylvania
	Abington
	Rosenfeld Cancer Center at Abington Memorial Hospital
		Clinical Trials Office - Rosenfeld Cancer Center at Abington Memorial Hospital	Ph:  215-481-2402
	Hershey
	Penn State Cancer Institute at Milton S. Hershey Medical Center
		Clinical Trials Office - Penn State Cancer Institute at Milton S. Hershey Medical Center	Ph:  717-531-3779
			Email: CTO@hmc.psu.edu
	Lewistown
	Lewistown Hospital
		Yixing Jiang	Ph:  717-242-7143
	Philadelphia
	Fox Chase Cancer Center - Philadelphia
		Clinical Trials Office - Fox Chase Cancer Center - Philadelphia	Ph:  215-728-4790
	State College
	Mount Nittany Medical Center
		Yixing Jiang	Ph:  814-231-7000
	West Grove
	Jennersville Regional Hospital
		Clinical Trials Office - Jennersville Regional Hospital	Ph:  610-869-1396

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		2008-10-22
NCI Grant/Contract Number		CA21115