Panobinostat and Stereotactic Radiation Therapy in Treating Patients With Brain Tumors

NCT01324635 | Terminated Phase 1 DMC

• 3 other identifiers: 11D.1002010-38JT 2158
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label phase I clinical trial with two arms, representing single and fractionated radiation therapy (Figure 4.1). Within each arm the radiation dose is pre-determined and not escalated. Panobinostat will be administered orally 3 times a week for 2 weeks. Panobinostat will be dose-escalated independently in each arm. There is no intra-patient dose escalation. Recurrent gliomas (Arm A) will be treated according to the Jefferson protocol for re-irradiation, 10 fractions each of 3.5Gy delivered over 2 weeks. Panobinostat will be administered orally three times a week for 2 weeks, starting on day 1 or 2 of radiation therapy. High-grade meningiomas (Arm A) will be treated with 6 weeks/30 fractions of fractionated radiation therapy, to a total dose of between 54 Gy and 60 Gy in fractions of either 1.8Gy or 2Gy. Panobinostat will be administered orally three times a week for 2 weeks, starting on the day of 1st fraction of radiation. Large brain metastases (Arm B) will be treated with a single fraction of radiosurgery. Panobinostat will be administered orally three times a week for 2 weeks, starting on the day of radiation. The radiosurgery may be delivered by either LINAC, gamma-knife, cyber-knife or tomotherapy technology.

Conditions

Recurrent Glioma; High-grade Meningioma; Brain Metastasis

Keywords

glioma; meningioma; brain metastasis; stereotactic; radiotherapy; radiosurgery

Outcome Measures

Primary Outcomes (6)

• Maximum tolerated does (MTD) of panobinostat, defined as one level below at which 2 of 6 patients experience a dose-limiting toxicity (DLT)

  Assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  Up to 30 days after the completion of study treatment

• Dose-limiting toxicities as defined by the NCI CTCAE version 4.0

  Up to 30 days after the completion of study treatment

• Overall survival

  Analyzed using Kaplan-Meier estimates

  Assessed up to 2 years

• Progression free survival (PFS)

  Analyzed using Kaplan-Meier estimates

  Assessed up to 2 years

• Response as defined by RECIST criteria

  A 2-sided exact 95% confidence interval will be computed.

  8 weeks after completion of study treatment

• Response as defined by RECIST criteria

  A 2-sided exact 95% confidence interval will be computed.

  Assessed up to 2 years

Study Arms (2)

Arm A (panobinostat, multiple fractions of SBRT)

EXPERIMENTAL

Patients receive panobinostat PO thrice weekly for 2 weeks and undergo 10 fractions of SBRT over 2 weeks (recurrent gliomas) OR 30 fractions of SBRT over 6 weeks (high grade meningiomas).

Drug: Panobinostat; Radiation: Stereotactic body radiation therapy; Procedure: Quality-of-life assessment

Arm B (panobinostat, stereotactic radiosurgery)

EXPERIMENTAL

Patients receive panobinostat as in Arm A and undergo a single fraction of stereotactic radiosurgery on day 1 of week 1.

Drug: Panobinostat; Procedure: Quality-of-life assessment; Radiation: Stereotactic radiosurgery

Interventions

Panobinostat DRUG

Given PO

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

Arm A (panobinostat, multiple fractions of SBRT); Arm B (panobinostat, stereotactic radiosurgery)

Stereotactic body radiation therapy RADIATION

Undergo SBRT

Also known as: SBRT, stereotactic radiation therapy, stereotactic radiotherapy

Arm A (panobinostat, multiple fractions of SBRT)

Quality-of-life assessment PROCEDURE

Ancillary studies

Also known as: quality of life assessment

Arm A (panobinostat, multiple fractions of SBRT); Arm B (panobinostat, stereotactic radiosurgery)

Stereotactic radiosurgery RADIATION

Undergo stereotactic radiosurgery

Arm B (panobinostat, stereotactic radiosurgery)

Eligibility Criteria

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

You may qualify if:

• Patient age is \> or = 18 years
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of \< or = 2
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Patients must meet the following laboratory criteria:
• Hematology:
• Neutrophil count of \> 1500/mm3
• Platelet count of \> 100,000/mm3L
• Hemoglobin \> or = 9 g/dL
• Biochemistry:
• AST/SGOT and ALT/SGPT \< or = 2.5 x upper limit of normal (ULN) or \< or = 5.0 x ULN if the transaminase elevation is due to disease involvement
• Serum bilirubin \< or = 1.5 x ULN
• Serum creatinine \< or = 1.5 x ULN or 24-hour creatinine clearance \> or = 50 ml/min
• Total serum calcium (corrected for serum albumin) or ionized calcium \> or = LLN
• Serum potassium \> or = LLN
• Serum sodium \> or = 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 panobinostat treatment
• Impaired cardiac function including any one of the following:
• History or presence of sustained ventricular tachyarrhythmia.
• Any history of ventricular fibrillation or torsade de pointes
• Bradycardia defined as HR \< 50 bpm. Patients with pacemakers are eligible if HR \> or = 50 bpm.
• Screening ECG with a QTc \> 450 msec
• Right bundle branch block + left anterior hemiblock (bifascicular block)
• Patients with myocardial infarction or unstable angina \< or = 6 months prior to starting study drug
• Other clinically significant heart disease (e.g., CHF NY Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
• Uncontrolled hypertension
• Concomitant use of drugs with a risk of causing torsades de pointes
• Patients with unresolved diarrhea \> or = grade 2
• 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)
• Other concurrent severe and/or uncontrolled medical conditions

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• Novartis: collaborator

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Glioma; Brain Neoplasms; Meningioma

Interventions

Panobinostat; Radiosurgery

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Vascular Tissue; Meningeal Neoplasms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Wenyin Shi, MD, PhD

  Thomas Jefferson 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

Study Record Dates

• First Submitted: March 17, 2011
• First Posted: March 29, 2011
• Study Start: May 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2016
• Last Updated: May 2, 2025

Record last verified: 2025-05

Locations

US (1)