LBH589, Paclitaxel, Carboplatin +/- Bevacizumab for Solid Tumors

NCT00556088 | Completed Phase 1

• 1 other identifier: SCRI REFMAL 121
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I protocol will evaluate the safety and tolerability of the combination of LBH589 and paclitaxel/carboplatin. The combination of LBH589, paclitaxel/carboplatin, and bevacizumab will also be evaluated for tolerability and preliminary antitumor activity in a subset of patients with advanced non-small cell lung cancer.

Conditions

Solid Tumors

Keywords

LBH589; Phase I; Solid Tumors; Paclitaxel; Carboplatin; Bevacizumab; Dose escalation

Outcome Measures

Primary Outcomes (1)

• Determine the maximally tolerated doses and dose limiting toxicities of LBH589 in combination with paclitaxel and carboplatin. Preliminary anti-tumor activity will also be assessed.

  18 months

Secondary Outcomes (1)

• Determine the tolerability and preliminary efficacy in a subset of patients with non-small cell lung cancer.

  18 months

Study Arms (1)

Part 1

EXPERIMENTAL

Part I Phase I dose escalation trial. LBH589 will be administered orally on Monday and Thursday or Tuesday and Friday each week (twice weekly). Paclitaxel and carboplatin will be administered intravenously every 21 days. Part II LBH589, paclitaxel, and carboplatin dosing will be determined in the first phase of this study (Phase I). The drug dosages to be administered will be reduced one level from the determined Maximum Tolerated Dose (MTD). In addition, bevacizumab 15 mg/kg will be added to the second portion of this trial.

Drug: LBH589, Paclitaxel, Carboplatin, Bevacizumab

Interventions

LBH589, Paclitaxel, Carboplatin, Bevacizumab DRUG

LBH589 will be administered orally twice weekly. Paclitaxel and carboplatin will be administered intravenously every 21 days. Once the MTD is established, drug dosages will be adjusted downward by one dose level and bevacizumab 15mg/kg intravenously every 3 weeks will be administered to a subset of patients with non-small cell lung cancer.

Part 1

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 paclitaxel and carboplatin is clinically appropriate for example, non-small cell lung, breast, ovarian, head and neck cancer, and carcinoma of unknown primary.
• 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 \<= upper limit normal (ULN) 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 Calcium \>= LLN Magnesium \>= LLN PT/INR and PTT \<= 1.5 x ULN
• Peripheral neuropathy \< grade 1.
• Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment.
• Life expectancy \> 12 weeks.
• Accessible for treatment and follow-up.
• All patients must be able to understand the nature of the study and give written informed consent prior to study entry.

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 \[See Appendix B\]).
• Right bundle branch block and left anterior hemiblock (bifasicular block).
• Atrial fibrillation or flutter.
• Uncontrolled hypertension (systolic blood pressure \[BP\] 160 or diastolic BP \>95mm 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; Paclitaxel; Carboplatin; Bevacizumab

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Howard A. Burris, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 8, 2007
• First Posted: November 9, 2007
• Study Start: December 1, 2007
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: December 30, 2010

Record last verified: 2010-12

Locations

US (1)