Sorafenib, Cetuximab, and Irinotecan in Treating Patients With Advanced or Metastatic Colorectal Cancer
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage III Colon Cancer
Stage III Rectal Cancer
Stage IV Colon Cancer
Stage IV Rectal Cancer
Drug: sorafenib tosylate
Drug: irinotecan hydrochloride
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Toxicity spectrum and dose-limiting toxicities of sorafenib in combination with cetuximab and irinotecan as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v 3.0 [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]
- Recommended dose for phase II evaluation of the combination of sorafenib, cetuximab and irinotecan [ Time Frame: 56 days ] [ Designated as safety issue: No ]
- Clinical activity of the combination of sorafenib, cetuximab and irinotecan in terms of radiological response [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
- Pharmacokinetics of sorafenib, cetuximab, and irinotecan when given in combination or when given in combination with cetuximab alone and with cetuximab and irinotecan [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
- Pharmacodynamics of the combination of irinotecan when given in combination with sorafenib and cetuximab in tumor tissues [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
|Study Start Date:||June 2005|
|Study Completion Date:||December 2011|
|Primary Completion Date:||September 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment (sorafenib, irinotecan, cetuximab)
Patients will receive sorafenib by mouth once or twice a day and a 1- to 2-hour infusion of cetuximab once a week for 8 weeks. They will also receive a 1½-hour infusion of irinotecan once a week in weeks 3-6. Patients will then receive sorafenib by mouth once or twice a day and a 1- to 2-hour infusion of cetuximab once a week for 6 weeks. They will also receive a 1½-hour infusion of irinotecan once a week in weeks 1-4. Treatment may repeat every 6 weeks for as long as benefit is shown.
Drug: sorafenib tosylate
Other Names:Drug: cetuximab
Other Names:Drug: irinotecan hydrochloride
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00134069
|United States, Colorado|
|University of Colorado at Denver Health Sciences Center|
|Aurora, Colorado, United States, 80045|
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21287-8936|
|Principal Investigator:||Wells Messersmith||University of Colorado at Denver Health Sciences Center|