Sorafenib, Cetuximab, and Irinotecan in Treating Patients With Advanced or Metastatic Colorectal Cancer

Recurrent Rectal Cancer Clinical Trial

Official title: Phase I/II Clinical, Pharmacological, and Biological Study of BAY 43-9006 in Combination With Cetuximab and Irinotecan in Patients With Advanced Colorectal Cancer

Status Completed

Clinical Trial Summary

This phase I/II trial is studying the side effects and best dose of sorafenib when given together with cetuximab and irinotecan and to see how well they work in treating patients with advanced or metastatic colorectal cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Sorafenib and cetuximab may also stop tumor growth by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, work in different ways to kill tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with cetuximab and irinotecan may kill more tumor cells

Clinical Trial Description

OBJECTIVES:

I. Determine the toxicity spectrum and dose-limiting toxic effects of sorafenib when combined with cetuximab and irinotecan in patients with advanced or metastatic colorectal cancer.

II. Determine the recommended phase II dose of sorafenib when combined with cetuximab and irinotecan in these patients.

III. Correlate the clinical activity of this regimen, in terms of radiologic and positron emission tomography (PET) response, with baseline extracellular signal-regulated kinase (ERK) expression as well as Kirsten rat sarcoma (KRAS), BRAF, and other genetic properties of tumors in these patients.

IV. Determine the pharmacokinetics of this regimen in these patients. V. Correlate the pharmacodynamic effects of this regimen with baseline ERK expression as well as KRAS, BRAF, and other genetic properties of tumors in these patients.

VI. Correlate the pharmacodynamic effects of this regimen on mitogen-activated protein kinase (MAPK) status in peripheral blood mononuclear cells and on normal skin and oral mucosa with clinical parameters in these patients.

OUTLINE: This is a phase I dose-escalation study of sorafenib followed by a multicenter phase II study.

PHASE I:

COURSE 1 (56 days): Patients receive oral sorafenib once or twice daily on days 1-56, cetuximab IV over 1-2 hours on days 1, 8,15, 22, 29, 36, 43, and 50, and irinotecan IV over 90 minutes on days 15, 22, 29, and 36.

COURSE 2 AND ALL SUBSEQUENT COURSES (42 days): Patients receive oral sorafenib once or twice daily on days 1-42, cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36, and irinotecan IV over 90 minutes on days 1, 8, 15, and 22. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

PHASE II: Patients receive sorafenib at the MTD determined in phase I, cetuximab, and irinotecan as in phase I.

After completion of study treatment, patients are followed at 30 days.

*NOTE: This trial was intended to be Phase I/II, but the trial never continued to the Phase II portion. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Rectal Neoplasms
• Recurrent Colon Cancer
• Recurrent Rectal Cancer
• Stage III Colon Cancer
• Stage III Rectal Cancer
• Stage IV Colon Cancer
• Stage IV Rectal Cancer

• NCT number: NCT00134069
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 1
• Start date: June 2005
• Completion date: December 2011