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

Stopped early · Phase 1

Conditions studied: Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer

In brief

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.

Key facts

Study ID

NCT01238965

Run by

University of Southern California

People needed

7

Starts

2010-10-01

Expected to finish

2015-04-01

Last updated by the study team

2015-05-27

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have histologically or cytologically confirmed advanced/metastatic colorectal cancer
• Must have measurable disease
• Must have received prior therapy (in any setting) with 5-FU, CPT-11, and oxaliplatin; (may have received prior erbitux and bevacizumab, but it is not required)
• Must have received at least one prior chemotherapy regimen for advanced disease
• Tumor must be accessible for core biopsy at the beginning of treatment and patients have a high intratumoral TS expression level prior to the beginning of treatment
• Life expectancy of > 12 weeks
• ECOG performance status 0-2 (Karnofsky >= 50%)
• Normal organ and marrow function as defined below:
• Serum albumin >= 3g/dL
• AST/SGOT and ALT/SGPT =< 2.5 x upper limit of normal(ULN)or =< 5.0 x ULN if the transaminase elevation is due to liver metastasis
• Serum bilirubin =< 1.5 x ULN
• Serum creatinine =< 1.5 x ULN or 24-hr creatinine clearance >= 50 ml/min
• Serum potassium >= LLN
• Serum phosphorous >= LLN
• Serum total calcium (corrected for serum albumin) or serum ionized calcium >= LLN
• Serum magnesium >= LLN
• TSH and free T4 within normal limits(WNL)(patients may be on thyroid hormone replacement)
• Leukocytes >= 3,000/μL
• Absolute neutrophil count >= 1,500/μL
• Platelets >= 100,000/μL
• Hemoglobin >= 9 mg/dL
• Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of LBH589 will be determined following review by the Principal Investigator
• Ability to understand and willing to sign a written informed consent document
• INR is =< 1.5 times ULN unless receiving therapeutic anticoagulation
• Patient is highly unlikely to conceive as indicated by at least one "yes" answer to the following questions:

You may not qualify if…

• Male patients whose sexual partners are WOCBP not using effective birth control
• May not have received any other investigational agents within 28 days of study entry (chemotherapy, any investigational drug or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy).
• May not receive other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study
• Patients with known brain metastases are excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to LBH589; including sodium butyrate, trichostatin A (TSA), trapoxin (TPX), MS-27-275 and depsipeptide
• Severe and/or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breast feeding or patients of reproductive potential not using two effective methods of birth control; women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589
• History of another primary malignancy within 5 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin
• Unresolved diarrhea > CTCAE grade 1
• Acute infection requiring intravenous antibiotic, antiviral, or antifungal medications within 2 weeks prior to the start of study drugs
• Known positivity for human immunodeficiency virus (HIV) or hepatitis C
• Screening ECG with a QTc > 450 msec
• Patients with congenital long QT syndrome
• History of sustained ventricular tachycardia
• Any history of ventricular fibrillation or torsades de pointes
• Bradycardia defined as heart rate < 50 beats per minute; patients with a pacemaker and heart rate >= 50 beats per minute are eligible
• Myocardial infarction or unstable angina within 6 months of study entry
• Congestive heart failure (NY Heart Association class III or IV)
• Right bundle branch block and left anterior hemiblock (bifascicular block)
• Prior cancer treatment with an HDAC inhibitor (e.g., vorinostat, Depsipeptide, MS-275, LAQ-824, PXD-101, and valproic acid)
• Uncontrolled hypertension
• Concomitant use of drugs with a risk of causing torsades de pointes
• Any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection)
• Patients needing valproic acid for any medical condition during the study or within 5 days prior to first LBH589

Where it is running

• USC/Norris Comprehensive Cancer Center — Los Angeles, California, United States

Full record on ClinicalTrials.gov

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