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

NCT01238965 | Terminated Phase 1 DMC

• 2 other identifiers: 3C-08-1NCI-2010-02149
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• To assess the safety of this regimen

  Up to 12 months

Secondary Outcomes (3)

• Time to progression

  At 3, 6, 9, and 12 months

• Overall response rate

  Every 2 months until disease recurrence or progression

• Overall survival

  At 3, 6, 9, and 12 months

Study Arms (1)

Arm I

EXPERIMENTAL

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: 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

Interventions

panobinostat DRUG

Given orally

Also known as: Faridak, HDAC inhibitor LBH589, histone deacetylase inhibitor LBH589, LBH589

Arm I

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU, Adrucil, Efudex, FU

Arm I

leucovorin calcium DRUG

Given IV

Also known as: calcium folinate, CF, CFR, citrovorum factor, LV, Wellcovorin

Arm I

biopsy PROCEDURE

Correlative studies

Also known as: biopsies

Arm I

reverse transcriptase-polymerase chain reaction GENETIC

Correlative studies

Also known as: RT-PCR

Arm I

western blotting GENETIC

Correlative studies

Also known as: Blotting, Western, Western Blot

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

gene expression analysis GENETIC

Correlative studies

Arm I

RNA analysis GENETIC

Correlative studies

Arm I

polymorphism analysis GENETIC

Correlative studies

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• University of Southern California: lead
• Novartis: collaborator

Study Sites (1)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Panobinostat; Fluorouracil; Leucovorin; Biopsy; Reverse Transcriptase Polymerase Chain Reaction; Blotting, Western; Gene Expression Profiling; Amplified Fragment Length Polymorphism Analysis

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Genetic Techniques; Electrophoresis; Chemistry Techniques, Analytical; Electrochemical Techniques; Immunoblotting; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; DNA Fingerprinting

Study Officials

• Heinz-Josef Lenz

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2010
• First Posted: November 11, 2010
• Study Start: October 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: April 1, 2015
• Last Updated: May 27, 2015

Record last verified: 2015-05

Locations

US (1)