Panobinostat and Fluorouracil Followed By Leucovorin Calcium in Treating Patients With Stage IV Colorectal Cancer Who Did Not Respond to Previous Fluorouracil-Based Chemotherapy
|ClinicalTrials.gov Identifier: NCT01238965|
Recruitment Status : Terminated (Adverse Events)
First Posted : November 11, 2010
Last Update Posted : May 27, 2015
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Colon Cancer Recurrent Rectal Cancer Stage IV Colon Cancer Stage IV Rectal Cancer||Drug: panobinostat Drug: fluorouracil Drug: leucovorin calcium Procedure: biopsy Genetic: reverse transcriptase-polymerase chain reaction Genetic: western blotting Other: laboratory biomarker analysis Genetic: gene expression analysis Genetic: RNA analysis Genetic: polymorphism analysis||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||7 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||October 2010|
|Actual Primary Completion Date :||December 2014|
|Actual Study Completion Date :||April 2015|
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.
Drug: leucovorin calcium
Other Name: biopsies
Genetic: reverse transcriptase-polymerase chain reaction
Other Name: RT-PCR
Genetic: western blotting
Other: laboratory biomarker analysis
Genetic: gene expression analysis
Genetic: RNA analysis
Genetic: polymorphism analysis
- To assess the safety of this regimen [ Time Frame: Up to 12 months ]
- Time to progression [ Time Frame: At 3, 6, 9, and 12 months ]
- Overall response rate [ Time Frame: Every 2 months until disease recurrence or progression ]
- Overall survival [ Time Frame: At 3, 6, 9, and 12 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01238965
|United States, California|
|USC/Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|Principal Investigator:||Heinz-Josef Lenz||University of Southern California|