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 Colon Cancer
Recurrent Rectal Cancer
Stage IV Colon Cancer
Stage IV Rectal Cancer
Drug: leucovorin calcium
Genetic: reverse transcriptase-polymerase chain reaction
Genetic: western blotting
Other: laboratory biomarker analysis
Genetic: gene expression analysis
Genetic: RNA analysis
Genetic: polymorphism analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- To assess the safety of this regimen [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
- Time to progression [ Time Frame: At 3, 6, 9, and 12 months ] [ Designated as safety issue: No ]
- Overall response rate [ Time Frame: Every 2 months until disease recurrence or progression ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: At 3, 6, 9, and 12 months ] [ Designated as safety issue: No ]
|Study Start Date:||October 2010|
|Study Completion Date:||April 2015|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I
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.
Other Names:Drug: fluorouracil
Other Names:Drug: leucovorin calcium
Other Names:Procedure: biopsy
Other Name: biopsiesGenetic: reverse transcriptase-polymerase chain reaction
Other Name: RT-PCRGenetic: western blotting
Other Names:Other: laboratory biomarker analysis
Correlative studiesGenetic: gene expression analysis
Correlative studiesGenetic: RNA analysis
Correlative studiesGenetic: polymorphism analysis
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01238965
|United States, California|
|USC/Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|Principal Investigator:||Heinz-Josef Lenz||University of Southern California|