Panobinostat and Fluorouracil Followed By Leucovorin Calcium in Treating Patients With Stage IV Colorectal Cancer Who Did Not Respond to Previous Fluorouracil-Based Chemotherapy

Recurrent Rectal Cancer Clinical Trial

Official title: Phase I Clinical Trial With LBH589 and Infusional 5-FU/LV in Patients With Metastatic Colorectal Cancer Who Failed 5-FU Based Chemotherapy

Status Terminated

Clinical Trial Summary

Panobinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panobinostat together with fluorouracil and leucovorin calcium may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and the best dose of giving panobinostat, fluorouracil, and leucovorin calcium together in treating patients with stage IV colorectal cancer who did not respond to previous fluorouracil-based chemotherapy.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the safety and feasibility of combining LBH589 with infusional 5-FU chemotherapy in the treatment of Stage IV colorectal cancer patients who have progressed on standard 5-FU regimens.

II. To determine the efficacy of LBH589 alone to produce consistent decreases in tumor thymidylate synthase (TS) expression.

SECONDARY OBJECTIVES:

I. To determine the time to tumor progression, progression free and overall survival of patients with advanced or metastatic colorectal cancer treated with LBH589 combined with infusional 5-FU.

II. To determine if TS repression by LBH589 predicts response to the combination of LBH589 and infusional 5-FU in patients who have already progressed on standard regimens containing 5-FU.

III. To obtain preliminary data on gene expression levels of TS, DPD and TP as well as germline polymorphisms of TS being associated with clinical outcome and toxicity.

IV. To obtain preliminary data on acetylation on peripheral blood mononuclear cells to establish biological activity in these patients at time of biopsies.

OUTLINE: Patients receive oral panobinostat 3 times a week. Patients also receive leucovorin calcium IV over 2 hours on days 1 and 15 followed by fluorouracil IV continuously over 46 hours on days 1-2 and 15-16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Rectal Neoplasms
• Recurrent Colon Cancer
• Recurrent Rectal Cancer
• Stage IV Colon Cancer
• Stage IV Rectal Cancer

• NCT number: NCT01238965
• Study type: Interventional
• Source: University of Southern California
• Status: Terminated
• Phase: Phase 1
• Start date: October 2010
• Completion date: April 2015