Sorafenib, Cetuximab, and Irinotecan in Treating Patients With Advanced or Metastatic Colorectal Cancer

NCT00134069 | Completed Phase 1 DMC

• 4 other identifiers: NCI-2009-0011007-0571R21CA117125U01CA070095
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/II trial is studying the side effects and best dose of sorafenib when given together with cetuximab and irinotecan and to see how well they work in treating patients with advanced or metastatic colorectal cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, 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 and cetuximab may also stop tumor growth by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, work in different ways to kill tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with cetuximab and irinotecan may kill more tumor cells

Conditions

Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage III Colon Cancer; Stage III Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

Outcome Measures

Primary Outcomes (5)

• Toxicity spectrum and dose-limiting toxicities of sorafenib in combination with cetuximab and irinotecan as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v 3.0

  Up to 30 days

• Recommended dose for phase II evaluation of the combination of sorafenib, cetuximab and irinotecan

  56 days

• Clinical activity of the combination of sorafenib, cetuximab and irinotecan in terms of radiological response

  Up to 30 days

• Pharmacokinetics of sorafenib, cetuximab, and irinotecan when given in combination or when given in combination with cetuximab alone and with cetuximab and irinotecan

  Up to 30 days

• Pharmacodynamics of the combination of irinotecan when given in combination with sorafenib and cetuximab in tumor tissues

  Up to 30 days

Study Arms (1)

Treatment (sorafenib, irinotecan, cetuximab)

EXPERIMENTAL

Patients will receive sorafenib by mouth once or twice a day and a 1- to 2-hour infusion of cetuximab once a week for 8 weeks. They will also receive a 1½-hour infusion of irinotecan once a week in weeks 3-6. Patients will then receive sorafenib by mouth once or twice a day and a 1- to 2-hour infusion of cetuximab once a week for 6 weeks. They will also receive a 1½-hour infusion of irinotecan once a week in weeks 1-4. Treatment may repeat every 6 weeks for as long as benefit is shown.

Drug: sorafenib tosylate; Drug: cetuximab; Drug: irinotecan hydrochloride

Interventions

sorafenib tosylate DRUG

Given orally

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

Treatment (sorafenib, irinotecan, cetuximab)

cetuximab DRUG

Given IV

Also known as: C225, C225 monoclonal antibody, IMC-C225, MOAB C225, monoclonal antibody C225

Treatment (sorafenib, irinotecan, cetuximab)

irinotecan hydrochloride DRUG

Given IV

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

Treatment (sorafenib, irinotecan, cetuximab)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed colorectal cancer (advanced or metastatic disease not amenable to potential curative resection)
• Archival tumor (blocks and/or slides) must be available for patients who decline tumor biopsies
• Tumor must be amenable to sequential biopsies for patients willing to undergo tumor biopsy
• Must have evidence of disease progression after first-line chemotherapy for advanced disease
• Previously irradiated lesions are not considered measurable disease
• Measurable disease, defined as \>= 1 unidimensionally measurable target lesion \>= 20 mm by conventional techniques OR \>= 10 mm by spiral CT scan
• No known brain metastases
• Eastern Cooperative Oncology Group (ECOG) 0-2 OR Karnofsky 60-100%
• Life expectancy of more than 12 weeks
• white blood cell count (WBC) \>= 3,000/mm\^3
• Bilirubin normal
• Creatinine normal OR creatinine clearance \>= 60 mL/min
• No hypertension
• No symptomatic congestive heart failure
• No unstable angina pectoris

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

University of Colorado at Denver Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287-8936, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Sorafenib; Cetuximab; Irinotecan

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)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids

Study Officials

• Wells Messersmith

  University of Colorado at Denver Health Sciences Center

  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: August 22, 2005
• First Posted: August 24, 2005
• Study Start: June 1, 2005
• Primary Completion: September 1, 2010
• Study Completion: December 1, 2011
• Last Updated: April 16, 2014

Record last verified: 2014-04

Locations

US (2)