NCT02041481

MEK Inhibitor MEK162 in Combination With Leucovorin Calcium, Fluorouracil, and Oxaliplatin in Treating Patients With Advanced Metastatic Colorectal Cancer

A Phase I Clinical Trial of MEK162 in Combination With FOLFOX in Patients With Advanced Metastatic Colorectal Cancer Who Failed Prior Standard Therapy

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of MEK inhibitor MEK162 when given together with leucovorin calcium, fluorouracil, and oxaliplatin in treating patients with advanced metastatic colorectal cancer. MEK inhibitor MEK162 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving MEK inhibitor MEK162 with leucovorin calcium, fluorouracil, and oxaliplatin may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD) for the combination of MEK162 (MEK inhibitor MEK162) plus leucovorin calcium, fluorouracil, oxaliplatin (FOLFOX) in patients with metastatic colorectal cancer. SECONDARY OBJECTIVES: I. Describe the safety of the combination of MEK162 across all investigated dose levels. II. Describe the pharmacokinetics of MEK162 and FOLFOX in 6 patients in the expanded MTD cohort. III. Describe any clinical activity to the combination using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. IV. Determine the recommended Phase II dose (RP2D) which may be less than the MTD for both intermittent and continuous dosing of MEK162. OUTLINE: This is a dose-escalation study of MEK inhibitor MEK162. Patients are assigned to 1 of 2 treatment arms. ARM I: Patients receive MEK inhibitor MEK162 orally (PO) twice daily (BID) on days 1-14, and leucovorin calcium intravenously (IV) over 2 hours, oxaliplatin IV over 2 hours, and fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive MEK inhibitor MEK162 PO BID on days 1-5, and leucovorin calcium IV over 2 hours, oxaliplatin IV over 2 hours, and fluorouracil IV continuously over 46 hours on days 6 and 7. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.

Conditions

• Recurrent Colon Cancer
• Recurrent Rectal Cancer
• Stage IVA Colon Cancer
• Stage IVA Rectal Cancer
• Stage IVB Colon Cancer
• Stage IVB Rectal Cancer

Interventions

Type	Name	Description
DRUG	MEK inhibitor MEK162	Given PO
DRUG	leucovorin calcium	Given IV
DRUG	fluorouracil	Given IV
DRUG	oxaliplatin	Given IV
OTHER	pharmacological study	Correlative studies
OTHER	Laboratory Biomarker Analysis	Correlative Studies

Timeline

• Start date: 2014-06-01
• Primary completion: 2018-01-19
• Completion: 2018-01-19
• First posted: 2014-01-22
• Last updated: 2018-01-25

Locations

1 site across 1 country: United States