A Panobinostat Presurgery

NCT01115036 | Withdrawn Phase 2

• 1 other identifier: Pro00020612
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

In the current study, the investigators will evaluate intratumoral pharmacodynamic and pharmacokinetic data associated with the administration of the HDACI, Panobinostat, among recurrent GBM patients. In addition, this study will evaluate the safety and tolerability of this agent, as well as evidence of anti-tumor activity in the patient population.

Conditions

Recurrent Glioblastoma

Keywords

glioblastoma; recurrent; surgical resection

Outcome Measures

Primary Outcomes (1)

• Anti-tumor Activity as Measured by Percentage of Patients Who Remain Progression-free after Six Months

  The primary objective will be to determine the anti-tumor activity of panobinostat among recurrent GBM patients as measured by the percentage of patients who remain progression-free after 6 months of therapy (PFS-6)

  18 months

Secondary Outcomes (3)

• Safety Evaluation of Panobinostat

  24 months

• Evaluation of Intratumoral Pharmacokinetics and Pharmacodynamics of Panobinostat

  24 months

• Evaluation of Systemic Pharmacokinetics

  24 months

Study Arms (1)

panobinostat

EXPERIMENTAL

Drug: panobinostat

Interventions

panobinostat DRUG

Oral panobinostat will be administered at 20mg by mouth 3 times a week one week prior to surgical resection. Within 2-6 weeks of resection, patients will resume panobinostat at 20mg 3 times per week. A cycle will be 28 days.

Also known as: LBH589

panobinostat

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 ≥ 18 years
• Histologically-confirmed grade 4 malignant glioma patients;
• Candidate for surgical resection of tumor;
• No more than 3 prior episodes of progressive disease;
• An interval of at least 4 weeks between prior surgical resection or two weeks from stereotactic biopsy;
• An interval of at least 12 weeks from the end of prior radiotherapy unless there is a new area of enhancement consistent with recurrent tumor outside of the radiation field, or there are progressive changes on MRI on at least two consecutive MRI scans at least four weeks apart, or there is biopsy-proven tumor progression;
• An interval of at least 4 weeks from prior chemotherapy (6 weeks for nitrosoureas) or investigational agent, unless the patient has recovered from all anticipated toxicities associated with that therapy;
• Karnofsky \* 70%;
• Hemoglobin ≥ 9 g/dL, ANC \> 1,500 cells/\*l, platelets \> 150,000 cells/\*l ;
• Serum creatinine \< 1.5 mg/dl or 24-hour creatinine clearance ≥ 50 ml/min, serum SGOT and bilirubin \< 1.5 times upper limit of normal; total serum calcium (corrected for serum albumin) or ionized calcium ≥ LLN; serum potassium ≥ LLN; serum sodium ≥ LLN; serum albumin ≥ LLN or 3g/dl;
• Clinically euthyroid (Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism);
• Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal;
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed;

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;
• Use of CYP-3A inducing anti-epileptics (phenytoin, fosphenytoin, carbamazepine, oxcarbazepine, phenobarbitol, primidone);
• Pregnancy or breast feeding;
• Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids;
• Active infection requiring intravenous antibiotics;
• Prior bevacizumab within 6 weeks of study enrollment;
• Therapeutic anti-coagulation with warfarin, aspirin, non-steroidal anti-inflammatory drugs or clopidogrel;
• Impaired cardiac function including any one of the following:
• Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (\<50 beats per minute), QTcF \> 450 msec on screening ECG, or right bundle branch block + left anterior hemiblock (bifascicular block);
• Presence of atrial fibrillation (ventricular heart rate \>100 bpm);
• Previous history angina pectoris or acute MI within 6 months;
• Congestive heart failure (New York Heart Association functional classification III-IV) or baseline MUGA/Echo shows LVEF \< 45%;
• Uncontrolled hypertension;
• Concomitant use of drugs with a risk of causing Torsades de pointes (See Table 14-1);

Sponsors & Collaborators

• Duke University: lead
• Novartis: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Glioblastoma; Recurrence

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• David A Reardon, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 30, 2010
• First Posted: May 3, 2010
• Study Start: April 1, 2010
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2012
• Last Updated: June 19, 2013

Record last verified: 2011-12

Locations

US (1)