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

NCT01383343 | Completed Phase 1

• 7 other identifiers: NCI-2011-02595CDR0000702751MC10178877P30CA015083U01CA069912UM1CA186686
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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)

  Graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  14 days

Secondary Outcomes (7)

• Incidence of adverse events of sorafenib tosylate in combination with bevacizumab and FOLFIRI as assessed by NCI CTCAE v 4.0

  Up to 3 months

• Response rate in patients treated with sorafenib tosylate in combination with FOLFIRI and bevacizumab, assessed using Response Evaluation Criteria in Solid Tumors

  From the start of the treatment until disease progression/recurrence, assessed up to 3 months

• Time to progression

  Up to 3 months

• Time to treatment failure

  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

  Up to 3 months

Study Arms (1)

Treatment (FOLFIRI and bevacizumab)

EXPERIMENTAL

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.

Biological: Bevacizumab; Drug: Fluorouracil; Drug: Irinotecan Hydrochloride; Drug: Leucovorin Calcium; Drug: Sorafenib Tosylate

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar FKB238, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF

Treatment (FOLFIRI and bevacizumab)

Fluorouracil DRUG

Given IV

Also known as: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (FOLFIRI and bevacizumab)

Irinotecan Hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, U-101440E

Treatment (FOLFIRI and bevacizumab)

Leucovorin Calcium DRUG

Given IV

Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Treatment (FOLFIRI and bevacizumab)

Sorafenib Tosylate DRUG

Given PO

Also known as: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

Treatment (FOLFIRI and bevacizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Fluorouracil; dehydroftorafur; Irinotecan; Leucovorin; Sorafenib

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Study Officials

• Joleen Hubbard

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2011
• First Posted: June 28, 2011
• Study Start: August 1, 2011
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: April 19, 2017

Record last verified: 2017-04

Locations

US (3)