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 colorectal cancer that has spread to other parts of the body. 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, by stopping them from dividing, or by stopping them from spreading. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Sorafenib tosylate and bevacizumab may also block tumor growth in different ways by targeting certain cells. Giving sorafenib tosylate and bevacizumab together with combination chemotherapy may be a better treatment for colorectal cancer.
Recurrent Colon Carcinoma
Recurrent Rectal Carcinoma
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|
- Maximum tolerated dose of sorafenib tosylate in combination with FOLFIRI and bevacizumab, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]Graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
- Incidence of adverse events 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 ]The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.
- Response rate in patients treated with sorafenib tosylate in combination with FOLFIRI and bevacizumab, assessed using Response Evaluation Criteria in Solid Tumors [ Time Frame: From the start of the treatment until disease progression/recurrence, assessed 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).
- Time until any treatment related toxicity evaluated via the ordinal Common Toxicity Criteria (CTC) standard toxicity grading [ 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.
- Time to until treatment related grade 3+ toxicity assessed via CTC standard toxicity grading [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]Will be assessed using continuous variables as the outcome measures (primarily nadir). 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.
- Time until hematologic nadirs (ANC, platelets, hemoglobin) [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]Descriptive statistics and simple scatter plots will form the basis of presentation of these data.
- Time to progression [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
- Time to treatment failure [ Time Frame: Time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months ] [ Designated as safety issue: No ]
|Study Start Date:||August 2011|
|Estimated Primary Completion Date:||November 2014 (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
Given IVDrug: Sorafenib Tosylate
Other Names:Biological: Bevacizumab
Other Names:Drug: Leucovorin Calcium
Other Name: CFDrug: Fluorouracil
I. To determine the maximally tolerated dose of the combination of irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI) plus sorafenib (sorafenib tosylate) plus bevacizumab.
I. To assess the safety of FOLFIRI plus sorafenib 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 intravenously (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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01383343
|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|