Sorafenib Tosylate, Bevacizumab, Irinotecan Hydrochloride, Leucovorin Calcium, and Fluorouracil in Treating Patients With Metastatic Colorectal Cancer

Completed · Phase 1

Conditions studied: Recurrent Colon Carcinoma, Recurrent Rectal Carcinoma, Stage IVA Colon Cancer, Stage IVA Rectal Cancer, Stage IVB Colon Cancer, Stage IVB Rectal Cancer

In brief

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.

Key facts

Study ID

NCT01383343

Run by

National Cancer Institute (NCI)

People needed

17

Starts

2011-08-01

Expected to finish

2017-02-01

Last updated by the study team

2017-04-19

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• This trial is intended for gastrointestinal malignancies appropriate for irinotecan-based therapy; histologic proof of cancer that is now unresectable; if prior therapy was received, patients must have shown progressive disease during prior treatment or within 6 months of their most recent therapy
• Measurable disease or non-measurable disease
• Absolute neutrophil count (ANC) >= 1500/uL
• Platelet (PLT) >= 100,000/uL
• Hemoglobin (Hgb) >= 9.0 gm/dL
• Total bilirubin =< upper limit of normal (ULN)
• Alkaline phosphatase =< 3 x ULN
• Aspartate aminotransferase (AST) =< 3 x ULN OR AST =< 5 x ULN if liver involvement
• International normalized ratio (INR) < 1.5 unless patients are receiving anti-coagulation therapy; patients receiving anti-coagulation therapy with an agent such as warfarin or heparin are allowed to participate if INR =< 3.0
• Urine protein creatinine (UPC) ratio < 1 or urine dipstick < 2+
• NOTE: urine protein must be screened by urine analysis for UPC ratio or by dipstick; for UPC ratio >= 1.0, 24-hour urine protein must be obtained and the level should be < 1000 mg
• Creatinine =< 1.5 x ULN
• Calculated creatinine clearance must be >= 45 mL/min using the Cockcroft-Gault formula
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Ability to provide informed consent
• Willing to return to Mayo Clinic for follow up
• Life expectancy >= 84 days (3 months)
• Women of childbearing potential only: negative pregnancy test done =< 7 days prior to registration

You may not qualify if…

• Known standard therapy for patient's disease that is potentially curative
• Note:
• Prior treatment with irinotecan, 5-fluoruracil or bevacizumab is allowed
• Prior treatment with sorafenib is not allowed
• Inadequately controlled hypertension (systolic blood pressure of > 150 mmHg or diastolic pressure > 100 mmHg on anti-hypertensive medications)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• History of myocardial infarction or unstable angina =< 6 months prior to registration or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Heart failure New York Heart Association classification III or IV
• Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks =< 6 months prior to registration
• Any hemorrhage/bleeding event > grade 3 =< 4 weeks prior to registration
• Evidence or history of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation); NOTE: patients on full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks of low molecular weight heparin or warfarin and has an INR in the range of 2-3; aspirin doses > 325 mg PO daily are not allowed
• Active or recent hemoptysis (>= ½ teaspoon of bright red blood per episode) =< 30 days prior to registration
• Serious, non-healing wound, active ulcer, or untreated bone fracture; NOTE: patients with fractures secondary to metastatic disease are eligible after appropriate radiotherapy
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection), recent peripheral arterial thrombosis, symptomatic peripheral vascular disease =< 6 months prior to registration
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =< 6 months prior to registration
• Major surgical procedures, open biopsy, or significant traumatic injury =< 28 days prior to registration or anticipation of need for major surgical procedure during the course of the study; EXCEPTION: core biopsy or minor surgical procedure, including placement of a vascular access device, =< 7 days prior to registration is allowed
• Patients taking cytochrome P450 enzyme-inducing antiepileptic drugs =< 4 weeks prior to registration will be excluded (phenytoin, carbamazepine, phenobarbital, rifampin, or St. John's wort)
• Known or suspected allergy or hypersensitivity to any agent given in the course of this trial
• Any condition that impairs patient's ability to swallow whole pills
• Any malabsorption problem
• Any of the following prior therapies:
• Chemotherapy =< 14 days prior to registration
• Immunotherapy =< 28 days prior to registration
• Radiation therapy =< 28 days prior to registration
• Radiation to > 25% of bone marrow

Where it is running

• Mayo Clinic in Arizona — Scottsdale, Arizona, United States
• Mayo Clinic in Florida — Jacksonville, Florida, United States
• Mayo Clinic — Rochester, Minnesota, United States

Full record on ClinicalTrials.gov

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