High-Dose Vorinostat and Fractionated Stereotactic Body Radiation Therapy in Treating Patients With Recurrent Glioma

NCT01378481 | Terminated Phase 1

• 4 other identifiers: NCI-2012-0113911D.1019018P30CA056036
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to determine if an investigational cancer treatment called vorinostat combined with fractionated stereotactic radiation therapy (FSRT) is effective in treating recurrent high grade gliomas. The main goal of this research study is to determine the highest dose of vorinostat that can be given to patients with recurrent tumors. The study will also determine the potential side effects and safety of these treatment combinations. Vorinostat is a small molecule inhibitor of histone deacetylase (HDAC). HDAC inhibitors help unravel the deoxyribonucleic acid (DNA) of the cancer cells and make them more susceptible to the treatment with radiation.

Conditions

Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Neoplasm

Outcome Measures

Primary Outcomes (5)

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

  Analysis of study data will be descriptive, including summary tables of toxicity. An exploratory retrospective trend analysis will be performed assessing for a correlation between plasma drug level and toxicity, using exact logistic regression models.

  48 hours

• Dose limiting toxicities (grade 3 or higher) defined by Common Toxicity Criteria (CTC) version 4.0

  Analysis of study data will be descriptive, including summary tables of toxicity. An exploratory retrospective trend analysis will be performed assessing for a correlation between plasma drug level and toxicity, using exact logistic regression models.

  48 hours

• Overall survival (OS)

  Analysis of study data will be descriptive, including Kaplan-Meier estimates of survival outcomes.

  Up to 2 years

• Progression free survival (PFS)

  Analysis of study data will be descriptive, including Kaplan-Meier estimates of survival outcomes.

  Time from start of treatment to time to progression, up to 2 years

• Response rate defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

  Analysis of study data will be descriptive. A 2-sided exact 95% confidence interval of response rate will be computed.

  Up to 2 years

Study Arms (1)

Treatment (vorinostat, surgery, FSRT)

EXPERIMENTAL

Patients receive high-dose vorinostat PO at 48, 27, and 3 hours prior to surgery. Beginning 2-6 weeks later, patients receive vorinostat PO QD on days 1-3 in weeks 1-2and undergo fractionated stereotactic body radiation therapy on days 1-5 in weeks 1-2. Treatment continues in the absence of disease progression or unacceptable toxicity.

Drug: Vorinostat; Radiation: Stereotactic Radiosurgery; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery

Interventions

Vorinostat DRUG

Given PO

Also known as: L-001079038, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid

Treatment (vorinostat, surgery, FSRT)

Stereotactic Radiosurgery RADIATION

Undergo fractionated stereotactic radiation therapy

Also known as: SBRT, Stereotactic External Beam Irradiation, Stereotactic Radiation Therapy, Stereotactic Radiotherapy

Treatment (vorinostat, surgery, FSRT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (vorinostat, surgery, FSRT)

Pharmacological Study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (vorinostat, surgery, FSRT)

Therapeutic Conventional Surgery PROCEDURE

Undergo neurosurgery

Treatment (vorinostat, surgery, FSRT)

Eligibility Criteria

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

You may qualify if:

• Patients must have a previously histologically or cytologically confirmed glioma (astrocytic or oligodendroglial supratentorial tumors grades 3 or 4 according to the World Health Organization \[WHO\] 2007 classification) that has been previously treated with fractionated radiation therapy and now shows evidence of recurrence
• Patients must have recovered from the toxic effects of prior therapy
• Patients must have recovered from the effects of any prior surgery to any part of the body; there must be a minimum of 28 days from the day of surgery to the day of registration; for core or needle biopsy, a minimum of 7 days must have elapsed prior to registration
• Patients may have previously undergone more than one craniotomy
• Prior treatment with cytotoxic and biological agents is permissible; there should be at least a 2 week break between prior treatment and enrollment; (in the case of bevacizumab, since this trial involves surgery, at least 4 weeks should elapse between last dose of drug and enrollment, in the case of nitrosoureas or mitomycin C, at least 6 weeks)
• Prior treatment with fractionated radiation therapy (up to 60 Gray \[Gy\]) is an eligibility criterion, however this should have been completed \>= 4 weeks prior to enrollment and there should not have been a second course of fractionated radiotherapy to the supratentorial area
• One prior single fraction radiosurgical procedure within the treatment field is acceptable if V12 \< 5 cc (V12 is the volume of brain receiving 12 or more Gy); additional radiosurgical procedures outside of the treatment area are acceptable
• Patients should not have received prior histone deacetylase therapy (HDAC) therapy, an exception being the anti-seizure medicine valproic acid; however even valproic acid should not be given concurrently with vorinostat
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 2 months
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal

You may not qualify if:

• Patients who have had:
• Radiotherapy within 4 weeks
• Chemotherapy/biological agents (excluding bevacizumab, nitrosoureas and mitomycin C) within 2 weeks
• Bevacizumab within 4 weeks
• Nitrosoureas and mitomycin C within 6 weeks prior to entering the study
• Those who have not recovered from acute adverse events due to any prior therapeutic agents
• Patients may not be receiving any other investigational agents
• Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of \>= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days of registration
• A history of long QT syndrome, or corrected QTc (QTc) prolongations \> 470 ms at baseline
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or other HDAC inhibitor or other agents used in study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because vorinostat is an antineoplastic agent with the potential for teratogenic or abortifacient effects, class D; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat, breastfeeding should be discontinued if the mother is treated with vorinostat; these potential risks may also apply to other agents used in this study

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma; Glioblastoma; Gliosarcoma; Glioma; Brain Neoplasms

Interventions

Vorinostat; 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

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Wenyin Shi

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2011
• First Posted: June 22, 2011
• Study Start: June 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: December 23, 2014

Record last verified: 2014-03

Locations

US (1)