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 Temporarily closed 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

1. Compare overall 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.
2. Compare progression-free survival of patients treated with these regimens.
3. Compare objective tumor response (confirmed and unconfirmed, complete and partial response) in patients with measurable disease treated with these regimens.
4. 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



• 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

Outcomes

Overall survival

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: 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

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		2008-11-24
NCI Grant/Contract Number		CA32102

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