Sorafenib Tosylate, Bevacizumab, Irinotecan Hydrochloride, Leucovorin Calcium, and Fluorouracil in Treating Patients With Metastatic Colorectal Cancer
|ClinicalTrials.gov Identifier: NCT01383343|
Recruitment Status : Completed
First Posted : June 28, 2011
Last Update Posted : April 19, 2017
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Colon Carcinoma Recurrent Rectal Carcinoma Stage IVA Colon Cancer Stage IVA Rectal Cancer Stage IVB Colon Cancer Stage IVB Rectal Cancer||Biological: Bevacizumab Drug: Fluorouracil Drug: Irinotecan Hydrochloride Drug: Leucovorin Calcium Drug: Sorafenib Tosylate||Phase 1|
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. (Cohort study cancelled as of March 25, 2014)
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||17 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Trial of FOLFIRI in Combination With Sorafenib and Bevacizumab in Patients With Advanced Gastrointestinal Malignancies|
|Study Start Date :||August 2011|
|Primary Completion Date :||February 2017|
|Study Completion Date :||February 2017|
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.
Other Names:Drug: Fluorouracil
Other Names:Drug: Irinotecan Hydrochloride
Other Names:Drug: Leucovorin Calcium
Other Names:Drug: Sorafenib Tosylate
- 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 ]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 ]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 ]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 to progression [ Time Frame: Up to 3 months ]
- 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 ]
- Time to until treatment related grade 3+ toxicity assessed via CTC standard toxicity grading [ Time Frame: Up to 3 months ]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 any treatment related toxicity evaluated via the ordinal Common Toxicity Criteria (CTC) standard toxicity grading [ Time Frame: Up to 3 months ]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 ]Descriptive statistics and simple scatter plots will form the basis of presentation of these data.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|