LBH589 and Gemcitabine in the Treatment of Solid Tumors

NCT00550199 | Terminated Phase 1

• 2 other identifiers: SCRI REFMAL 120IND 79,355
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a single center phase I dose escalation trial. LBH589 will be administered orally twice weekly. Gemcitabine will be administered intravenously over 30 minutes on days 1, 8, and 15 every 28 days. Dose escalation will begin at Dose Level 1. Three patients will be enrolled at each dose level. If 1/3 patients experiences dose-limiting toxicity, the dose level will be expanded to 6 patients. If 2/6 patients experience dose-limiting toxicity at a specific dose level, then the previous dose level will be considered the recommended phase II dose. Dose escalation will continue until the maximum tolerated dose is determined or until all dose levels outlined in the protocol have been completed. A total of 10 patients will be treated at the dose that is recommended for further phase II evaluation to further assess the safety of the combination regimen. Toxicity assessments will be ongoing and disease assessments will be repeated every 2 treatment cycles. Patients will be allowed to continue on study until disease progression unless toxicity warrants drug discontinuation.

Conditions

Solid Tumors

Keywords

Solid Tumors; Phase I; LBH589; Gemcitabine

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated doses and dose limiting toxicities of LBH589 in combination with gemcitabine when administered to patients with advanced incurable malignant solid tumors.

  18 months

Study Arms (1)

LBH589 and Gemcitabine

EXPERIMENTAL

Phase I dose escalation study

Drug: LBH589, Gemcitabine

Interventions

LBH589, Gemcitabine DRUG

Phase I dose escalation: LBH589 will be administered orally twice weekly. Gemcitabine will be administered intravenously over 30 minutes on days 1, 8, and 15 every 28 days.

LBH589 and Gemcitabine

Eligibility Criteria

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

You may qualify if:

• Histologically documented metastatic or locally advanced, incurable malignancy for which gemcitabine is clinically appropriate (e.g., non-small cell lung cancer, breast, ovarian, bladder cancer and lymphoma).
• Male or female patients aged ≥ 18 years old.
• Maximum of 3 prior regimens in a metastatic setting allowed and may include other targeted agents, immunotherapy and chemotherapy.
• Measurable disease by RECIST criteria.
• ECOG PS 0 or 1.
• Laboratory values as follows:
• ANC \> 1500/μL
• Hgb \> 9 g/dL
• Platelets \>100,000/uL
• Bilirubin \< 1.5 mg/dL
• AST/SGOT and ALT/SGPT \< 2.5 x ULN or \< 5.0 x ULN in patients with liver metastases
• Creatinine \< 2.0 mg/dL Or 24-hour Creatinine Clearance \> 50 ml/min
• Albumin \> 3 g/dL
• Potassium \> lower limit normal (LLN)
• Phosphorous \> LLN

You may not qualify if:

• Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer. Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
• Impaired cardiac function including any of the following:
• Screening ECG with a QTc \> 450 msec.
• 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 minutes. Patients wit 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 (bifasicular block).
• Atrial fibrillation or flutter.
• Uncontrolled hypertension (systolic blood pressure \[BP\] 180 or diastolic BP \>100mm Hg) or uncontrolled cardiac arrhythmias.
• Active CNS disease, including meningeal metastases.
• Known diagnosis of human immunodeficiency virus (HIV) infection.
• Unresolved diarrhea \> CTCAE grade 1.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Novartis: collaborator

Study Sites (1)

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

MeSH Terms

Interventions

Panobinostat; Gemcitabine

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Howard Burris, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

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: October 26, 2007
• First Posted: October 29, 2007
• Study Start: November 1, 2007
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: August 19, 2013

Record last verified: 2013-08

Locations

US (1)