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Phase III Randomized Study of Irinotecan Hydrochloride-Based Chemotherapy and Cetuximab With Versus Without Bevacizumab in Patients With Metastatic Colorectal Cancer That Progressed on First-Line Therapy (Treatment Arm III Closed to Accrual as of 4/20/2009)

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

Alternate Title

Irinotecan and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer That Progressed During First-Line Therapy

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs
Phase III Treatment Active 18 and over NCI SWOG-S0600
S0600, CALGB-SWOG-S0600, ECOG-SWOG-S0600, CAN-NCIC-SWOG-S0600, NCCTG-SWOG-S0600, NCT00499369

Special Category: NCI Web site featured trial, CTSU trial

Objectives

Compare progression-free survival of patients with metastatic colorectal cancer that progressed on first-line therapy comprising bevacizumab and FOLFOX, OPTIMOX, or XELOX treated with irinotecan hydrochloride-based chemotherapy and cetuximab with vs without bevacizumab.
Compare overall survival of patients treated with these regimens.
Compare objective tumor response (confirmed and unconfirmed, complete and partial response) in patients with measurable disease treated with these regimens.
Compare the tolerability and safety profile of these regimens in these patients.

Entry Criteria

Disease Characteristics:

Histologically or cytologically confirmed colorectal cancer, meeting the following criteria:
- Metastatic disease
  - Confirmation may be from either the primary tumor or a metastasis
- Progressed on first-line therapy comprising bevacizumab and FOLFOX, OPTIMOX, or XELOX
  - Progression occurred within 90 days after the last dose of bevacizumab AND within 28 days prior to study entry
  - Patients who discontinued oxaliplatin, but continued on fluorouracil/leucovorin calcium or capecitabine and bevacizumab and then had subsequent progression while on fluoropyrimidine and bevacizumab are eligible
- Wild type KRAS

Measurable or nonmeasurable disease

No history or known presence of brain metastases

Prior/Concurrent Therapy:

At least 14 days since the last dose of prior first-line chemotherapy and bevacizumab
At least 28 days since prior radiotherapy and recovered
At least 28 days since prior major surgery and recovered
No prior irinotecan hydrochloride (as adjuvant or metastatic treatment)
No prior cetuximab or other agents targeting VEGF or EGFR (except bevacizumab)
No other concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any other type of anticancer treatment
Concurrent full-dose anticoagulation with warfarin allowed provided INR is 2-3
Concurrent low-molecular weight heparin allowed

Patient Characteristics:

Zubrod performance status 0-2
Not pregnant or nursing
Fertile patients must use effective contraception during and for 4 months after completion of study treatment
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9 g/dL
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST or ALT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)
Creatinine normal OR creatinine clearance ≥ 60 mL/min
Urine protein:creatinine ratio ≤ 0.5 OR 24-hour urine protein < 1,000 mg
No nephrotic range proteinuria during prior bevacizumab therapy
No uncontrolled high blood pressure (BP) (i.e., systolic BP > 150 mm Hg and diastolic BP > 90 mm Hg)
No other malignancy within the past 5 years except for adequately treated basal or squamous cell skin cancer or cervical cancer in situ
No cardiovascular event within the past 6 months, including any of the following:
- Arterial thrombosis
- Unstable angina
- Myocardial infarction
- Cerebrovascular accident
No NYHA class II-IV congestive heart failure
No unstable symptomatic arrhythmia requiring medication
- Patients with chronic, controlled arrhythmias (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) are eligible
No clinically significant peripheral vascular disease
No serious or nonhealing active wound, ulcer, or bone fracture
No gastrointestinal (GI) perforation while on prior bevacizumab
No significant bleeding episodes (e.g., hemoptysis or upper or lower GI bleeding) within the past 6 months unless the source of bleeding has been resected
No known hypersensitivity to bevacizumab or known potential hypersensitivity to cetuximab
No clinically relevant bleeding diathesis or coagulopathy

Expected Enrollment

1260

Outcomes

Primary Outcome(s)

Overall survival

Secondary Outcome(s)

Progression-free survival
Objective tumor response
Tolerability and safety profile

Outline

This is a multicenter, randomized study. Patients are stratified according to Zubrod performance status (0 vs 1 or 2), discontinuation of oxaliplatin during first-line therapy (yes vs no), planned concurrent chemotherapy (FOLFIRI vs single-agent irinotecan hydrochloride), and time from last dose of bevacizumab (14-42 days vs ≥ 43 days).

All patients receive 1 of the following chemotherapy regimens:

Single-agent irinotecan hydrochloride: Patients receive irinotecan hydrochloride IV over 90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

FOLFIRI: Patients receive irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours on days 1 and 2. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive single-agent irinotecan hydrochloride or FOLFIRI as outlined above and cetuximab IV over 1-2 hours on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity.

Arm II: Patients receive single-agent irinotecan hydrochloride or FOLFIRI as outlined above and cetuximab as in arm I. Patients also receive bevacizumab IV over 30 minutes on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity.

Arm III (closed to accrual as of 4/20/2009): Patients receive single-agent irinotecan hydrochloride or FOLFIRI as outlined above and cetuximab as in arm I. Patients also receive a higher dose of bevacizumab (higher than in arm II) IV over 30 minutes on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months for up to 3 years.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Philip Gold, MD, Protocol chair
Ph: 206-386-2121
Email: philip.gold@swedish.org
Anthony Shields, MD, PhD, Protocol co-chair
Ph: 313-576-8735; 800-527-6266
Email: shieldsa@karmanos.org

North Central Cancer Treatment Group

Axel Grothey, MD, Protocol chair
Ph: 507-284-2511
Email: grothey.axel@mayo.edu

Cancer and Leukemia Group B

Leonard Saltz, MD, Protocol chair
Ph: 212-639-2501; 800-525-2225

Eastern Cooperative Oncology Group

Steven Cohen, MD, Protocol chair
Ph: 215-728-2450; 888-369-2427
Email: S_Cohen@fccc.edu

NCIC-Clinical Trials Group

Scott Berry, MD, Protocol chair
Ph: 416-480-4270

Trial Sites

U.S.A.

Arkansas

Ft. Smith

Hembree Mercy Cancer Center at St. Edward Mercy Medical Center

John Wells, MD
Ph: 479-484-4700

California

Los Angeles

USC/Norris Comprehensive Cancer Center and Hospital

Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital
Ph: 323-865-0451

Orange

Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center

Clinical Trials Office - Chao Family Comprehensive Cancer Center
Ph: 877-UC-STUDY

Email: ucstudy@uci.edu

Illinois

Decatur

Decatur Memorial Hospital Cancer Care Institute

Clinical Trials Office - Decatur Memorial Hospital Cancer Care Institute
Ph: 217-876-6601

Rockford

Swedish-American Regional Cancer Center

Clinical Trials Office - Swedish-American Regional Cancer Center
Ph: 815-489-4413

Iowa

Ames

McFarland Clinic, PC

Clinical Trials Office - McFarland Clinic, PC
Ph: 515-239-2621

Cedar Rapids

Cedar Rapids Oncology Associates

Clinical Trials Office - Cedar Rapids Oncology Associates
Ph: 319-363-2690

Mercy Regional Cancer Center at Mercy Medical Center

Martin Wiesenfeld, MD
Ph: 319-363-8303

Mason City

Mercy Cancer Center at Mercy Medical Center - North Iowa

Clinical Trials Office - Mercy Cancer Center at Mercy Medical Center - North Iowa
Ph: 641-422-6304

Ottumwa

McCreery Cancer Center at Ottumwa Regional

Robert Behrens
Ph: 641-684-2946

Louisiana

Baton Rouge

Mary Bird Perkins Cancer Center - Baton Rouge

Robert Veith
Ph: 225-767-0847

Pennington Cancer Center at Baton Rouge General

Clinical Trials Office - Pennington Cancer Center at Baton Rouge General
Ph: 225-381-6451

New Orleans

MBCCOP - LSU Health Sciences Center

Robert Veith
Ph: 504-568-5151

Medical Center of Louisiana - New Orleans

Robert Veith
Ph: 504-903-2311

Michigan

Kalamazoo

Borgess Medical Center

Raymond Lord, MD
Ph: 269-373-7458

Bronson Methodist Hospital

Raymond Lord, MD
Ph: 269-373-7458

West Michigan Cancer Center

Clinical Trials Office - West Michigan Cancer Center
Ph: 269-373-7458

New Jersey

Sparta

Frederick R. and Betty M. Smith Cancer Treatment Center

Edith Mitchell, MD, FACP
Ph: 215-955-8874

New York

Glens Falls

Charles R. Wood Cancer Center at Glens Falls Hospital

Clinical Trials Office - Charles R. Wood Cancer Center at Glens Falls Hospital
Ph: 518-926-6700

North Carolina

Kinston

Kinston Medical Specialists

Peter Watson, MD
Ph: 252-559-2200ext.201

North Dakota

Bismarck

Bismarck Cancer Center

Edward Wos, DO
Ph: 701-323-5741

Medcenter One Hospital Cancer Care Center

Edward Wos, DO
Ph: 701-323-5741

Mid Dakota Clinic, PC

Clinical Trials Office - Mid Dakota Clinic, PC
Ph: 701-530-6950

St. Alexius Medical Center Cancer Center

Clinical Trials Office - St. Alexius Medical Center Cancer Center
Ph: 701-530-6950

Ohio

Canton

Mercy Cancer Center at Mercy Medical Center

Mitchell Haut, MD
Ph: 330-453-9993

Oklahoma

Lawton

Cleo Craig Cancer Research Clinic

Nadim Nimeh, MD
Ph: 580-536-2121ext.113

Pennsylvania

Darby

Mercy Fitzgerald Hospital

Clinical Trials Office - Mercy Fitzgerald Hospital
Ph: 610-237-4982

Media

Riddle Memorial Hospital Cancer Center

Edith Mitchell, MD, FACP
Ph: 215-955-8874

Philadelphia

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Clinical Trials Office - Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
Ph: 215-955-6084

Scranton

Hematology and Oncology Associates of Northeastern Pennsylvania

Edith Mitchell, MD, FACP
Ph: 215-955-8874

Tennessee

Memphis

University of Tennessee Cancer Institute - Memphis

Clinical Trials Office - University of Tennessee Cancer Institute
Ph: 901-448-3303

Wisconsin

Chippewa Falls

Marshfield Clinic - Chippewa Center

Adedayo Onitilo
Ph: 715-726-4200
800-334-4535

Eau Claire

Marshfield Clinic Cancer Care at Regional Cancer Center

Adedayo Onitilo
Ph: 715-387-5426

Elkhorn

Vince Lombardi Cancer Center at Aurora Lakeland Medical Center - Elkhorn

Rossana Madamba
Ph: 262-741-2671
800-252-2990

Glendale

Oncology Alliance, SC - Milwaukee - East

Clinical Trials Office - Oncology Alliance, SC - Milwaukee - East
Ph: 414-906-4480

La Crosse

Gundersen Lutheran Center for Cancer and Blood

Clinical Trials Office - Gundersen Lutheran Cancer Center
Ph: 608-775-2385

Email: cancerctr@gundluth.org

Marshfield

Marshfield Clinic - Marshfield Center

Clinical Trials Office - Marshfield Clinic - Marshfield Center
Ph: 800-782-1581 ext. 94457

Saint Joseph's Hospital

Adedayo Onitilo
Ph: 715-387-1713

Milwaukee

Medical Consultants, Limited

Jonathan Treisman, MD
Ph: 414-385-3086

Minocqua

Marshfield Clinic - Lakeland Center

Adedayo Onitilo
Ph: 715-358-1000
800-347-0673

Rhinelander

Ministry Medical Group at Saint Mary's Hospital

Adedayo Onitilo
Ph: 715-361-4700
800-866-8673

Rice Lake

Marshfield Clinic - Indianhead Center

Adedayo Onitilo
Ph: 715-236-8100

Stevens Point

Saint Michael's Hospital Cancer Center

Adedayo Onitilo
Ph: 715-346-5000
800-472-9449

Wausau

Marshfield Clinic - Wausau Center

Adedayo Onitilo
Ph: 715-847-3000
800-847-0016

Weston

Marshfield Clinic - Weston Center

Adedayo Onitilo
Ph: 715-393-1000
888-782-8581

Wisconsin Rapids

Marshfield Clinic - Wisconsin Rapids Center

Adedayo Onitilo
Ph: 715-424-8600

Related Information

Featured trial article

Registry Information

Official Title		Phase III Trial of Irinotecan-Based Chemotherapy Plus Cetuximab (NSC-714682) With or Without Bevacizumab (NSC-704965) As Second-Line Therapy for Patients with Metastatic Colorectal Cancer Who Have Progressed on Bevacizumab with Either FOLFOX, OPTIMOX or XELOX

Trial Start Date		2007-06-15

Trial Completion Date		2010-01-15 (estimated)

Registered in ClinicalTrials.gov		NCT00499369

Date Submitted to PDQ		2007-05-17

Information Last Verified		2009-11-20

NCI Grant/Contract Number		CA32102

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.