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

• Status: Completed
• Trial end date: 2011-12-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Antibodies; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Camptothecin; Cetuximab; Immunoglobulins; Irinotecan; Niacinamide; Sorafenib

Criteria

Inclusion Criteria:

• 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

• No cardiac arrhythmia

• Not pregnant or nursing

• Able to swallow oral medication

• Willing to undergo 2 sequential tumor and skin biopsies

• No ongoing or active infection

• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drugs

• No psychiatric illness or social situation that would preclude study compliance

• No other uncontrolled illness

• No prior cetuximab

• No concurrent prophylactic filgrastim (G-CSF), sargramostim (GM-CSF) or epoetin alfa

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

• No other concurrent chemotherapy

• More than 4 weeks since prior radiotherapy and recovered

• No prior sorafenib

• No other prior therapy targeted against MAPK

• More than 14 days since prior and no concurrent administration of the following cytochrome P450 3A4 (CYP3A4) inducers:

• Rifampin

• Rifabutin

• Hypericum perforatum (St. John's wort)

• Phenytoin

• Carbamazepine

• Phenobarbital

• More than 7 days since prior and no concurrent administration of the following CYP3A4 inhibitors:

• Amiodarone

• Clarithromycin

• Diltiazem

• Erythromycin

• Grapefruit juice

• Indinavir

• Saquinavir

• Lopinavir in combination with ritonavir

• Fosamprenavir

• Ritonavir

• Atazanavir

• Nelfinavir

• Itraconazole

• Ketoconazole

• Nefazodone

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent investigational agents

• No other concurrent anticancer therapy

• Negative pregnancy test

• Fertile patients must use effective contraception

• Absolute neutrophil count >=1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• No evidence of bleeding diathesis

• Aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times upper limit of normal