Safety Study of Bevacizumab, Everolimus and LBH589 (BEL) for Advanced Solid Tumors

NCT01055795 | Completed Phase 1 DMC

• 1 other identifier: Pro00020190
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to test the safety of three study drugs, bevacizumab (Avastin™), Everolimus (Afinitor™) and LBH589 (Panobinostat) when they are given together. It is hoped this study drug combination might lead to a greater decrease the in size of the cancer and/or slow down how fast the cancer is growing compared to when these drugs are given alone. Subjects will be enrolled at Duke University Medical Center (DUMC).

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• To define the maximal tolerated dose (if any) and the recommended phase II dose for the triplet combination of everolimus plus LBH589 plus bevacizumab in subjects with advanced solid tumors

  3 years

Secondary Outcomes (4)

• To describe any dose limiting toxicities of this combination and to describe any non-dose limiting toxicities of this combination.

  3 years

• To describe pharmacokinetic characteristics of everolimus and LBH589 when the two drugs administered in combination.

  3 years

• To describe the effect of this treatment combination on blood based biomarkers for tumor angiogenesis and tumor growth factors.

  3 years

• To describe any signs of clinical activity of this treatment combination, including response rate, time to progression, and duration of response.

  3 years

Study Arms (1)

Bevacizumab, Everolimus and LBH589

EXPERIMENTAL

Dose Escalation Cohort #, Subjects, Bevacizumab, Everolimus, LBH589 1. 3-6, All study drugs administered per dose level 2. 3-6, All study drugs administered per dose level 3. 3-6, All study drugs administered per dose level Expanded Cohorts Cohort #, Subjects, Bevacizumab, Everolimus, LBH589 A, B \& C; 30, Recommended Phase II Dose for all three compounds

Drug: Bevacizumab, Everolimus and LBH589

Interventions

Bevacizumab, Everolimus and LBH589 DRUG

Dose Escalation Cohort #, Subjects, Bevacizumab, Everolimus, LBH589 1. 3-6, All study drugs administered per dose level 2. 3-6, All study drugs administered per dose level 3. 3-6, All study drugs administered per dose level Expanded Cohorts Cohort #, Subjects, Bevacizumab, Everolimus, LBH589 A, B \& C; 30, Recommended Phase II Dose for all three compounds

Bevacizumab, Everolimus and LBH589

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically and/or cytologically confirmed malignant solid tumor that is refractory to standard therapies, or for which no standard therapies exist.
• Patients must have at least one measurable site of disease according to RECIST (see Appendix 1) criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
• Age ≥ 18 years
• Karnofsky Performance status ≥ 80% (see Appendix 2)
• Adequate bone marrow function as shown by:
• ANC ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin \>9 g/dL; Erythropoietin and transfusion support is permitted provided treatments are not required more than every 8 weeks.
• Adequate liver function as shown by:
• serum bilirubin ≤ 1.5 x ULN
• INR ≤ 1.5
• ALT and AST ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases)
• Adequate renal function: creatinine clearance (estimated) ≥ 40 cc/min
• Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: Use of standard lipid lowering agents (see Section 10.3.6 for guidance) is permitted to meet eligibility.
• Fasting blood sugar \<160 mg/dL.

You may not qualify if:

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks from day 1 of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
• Patients who:
• have had a major surgery or significant traumatic injury within 4 weeks from day 1 of study drug,
• have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or
• are anticipated to require major surgery during the course of the study.
• Patients with a known hypersensitivity to experimental drugs (or classes of drugs) or their excipients
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent with the following exceptions:
• Intermittent steroids ( not to exceed 4 mg every day) may be used on an as-needed basis (e.g. treatment for chemotherapy-related nausea.)
• Patients on physiologic replacement doses of steroids due to adrenal insufficiency for any reason may remain on these medications.
• Topical, inhaled or intra-articular corticosteroids
• Patients should not receive immunization with attenuated live vaccines within one week of day 1 of study drug or during study period
• Active brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases. Treated, asymptomatic metastases are permitted provided the patient has been off steroids for at least 1 month prior to day 1 of study drug.
• Clinically significant arrhythmias including complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmias, 2nd degree AV block type II, 3rd degree AV block clinically significant resting bradycardia (\<50 beats per minute), QTcF \> 450 msec on screening ECG.
• Presence of poorly controlled atrial fibrillation (ventricular heart rate \>100 bpm)
• Previous history of CVA, TIA, angina pectoris, acute MI or history of recent re-perfusion procedures (e.g. PTCA) within 6 months from day 1 of study drug.

Sponsors & Collaborators

• Herbert Hurwitz: lead
• Novartis: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Interventions

Bevacizumab; Everolimus; Panobinostat

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sirolimus; Macrolides; Lactones; Organic Chemicals; Hydroxamic Acids; Hydroxylamines; Amines; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Herbert I Hurwitz, Md

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: January 24, 2010
• First Posted: January 26, 2010
• Study Start: March 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: May 1, 2012
• Last Updated: December 24, 2012

Record last verified: 2012-12

Locations

US (1)