Sorafenib Tosylate, Bevacizumab, Irinotecan Hydrochloride, Leucovorin Calcium, and Fluorouracil in Treating Patients With Metastatic Colorectal Cancer
This phase I trial studies the side effects and best dose of sorafenib tosylate when given together with bevacizumab, irinotecan hydrochloride, leucovorin calcium, and fluorouracil in treating patients with metastatic colorectal cancer. Drugs used in chemotherapy, such as irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, 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 tosylate and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib tosylate and bevacizumab together with combination chemotherapy may kill more tumor cells.
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage IVA Colon Cancer
Stage IVA Rectal Cancer
Stage IVB Colon Cancer
Stage IVB Rectal Cancer
Drug: irinotecan hydrochloride
Drug: sorafenib tosylate
Drug: leucovorin calcium
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of FOLFIRI in Combination With Sorafenib and Bevacizumab in Patients With Advanced Gastrointestinal Malignancies|
- MTD of sorafenib tosylate in combination with FOLFIRI and bevacizumab, determined according to incidence of DLT graded using NCI CTCAE version 4.0 [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
- Toxicity profile of sorafenib tosylate in combination with bevacizumab and FOLFIRI as assessed by NCI CTCAE v 4.0 [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
- Response rate in patients treated with sorafenib tosylate in combination with FOLFIRI and bevacizumab, assessed using RECIST [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).
|Study Start Date:||August 2011|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (FOLFIRI and bevacizumab)
Patients receive irinotecan hydrochloride IV over 90 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, fluorouracil IV continuously over 46 hours on days 1-2, bevacizumab IV over 30-90 minutes on day 1, and sorafenib tosylate PO QD or BID on days 3-6 and 10-13*. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Drug: irinotecan hydrochloride
Other Names:Drug: sorafenib tosylate
Other Names:Biological: bevacizumab
Other Names:Drug: leucovorin calcium
Other Names:Drug: fluorouracil
I. To determine the maximally tolerated dose of the combination of irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI) plus sorafenib tosylate plus bevacizumab.
I. To assess the safety of FOLFIRI plus sorafenib tosylate plus bevacizumab. II. To assess the feasibility of the proposed combination. III. To evaluate the response rate and identify any activity of the proposed combination.
OUTLINE: This is a dose-escalation study of sorafenib tosylate followed by a cohort study.
Patients receive irinotecan hydrochloride interavenously (IV) over 90 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, fluorouracil IV continuously over 46 hours on days 1-2, bevacizumab IV over 30-90 minutes on day 1, and sorafenib tosylate orally (PO) once (QD) or twice daily (BID) on days 3-6 and 10-13*. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
NOTE: * Patients may also receive sorafenib tosylate on days 7 and 14.
After completion of study therapy, patients are followed up for 3 months.
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Joleen Hubbard||Mayo Clinic|