Valproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors

NCT00302159 | Completed Phase 2 Results DMC

• 2 other identifiers: 06011206-C-0112
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 3

Brief Summary

Background:

• Radiation therapy with temozolomide (an anti-cancer drug) is standard therapy for treating brain tumors called glioblastomas.
• The drug valproic acid, currently approved for treating seizures, has been shown in laboratory tests to increase the radiosensitivity of glioma cells. Objectives:
• To determine the effectiveness of adding valproic acid to standard treatment with radiation therapy and temozolomide for treating glioblastoma. Eligibility:
• Patients 18 years of age and older with glioblastoma multiforme who have not been previously treated with chemotherapy of radiation. Design:
• This Phase II trial will enroll 41 patients.
• Patients will receive radiation therapy to the brain once a day, Monday through Friday, for 6 1/2 weeks.
• Patients will take temozolomide once a day by mouth, Monday through Friday, during the period of radiation treatment. Starting 4 weeks after radiation therapy, patients will take temozolomide once a day for 5 days every 28 days for a total of six cycles.
• Patients will receive valproic acid by mouth twice a day beginning 1 week prior to the first day of radiation therapy and continuing until the completion of chemotherapy and radiation therapy.
• Patients will have follow-up visits 1 month after completing therapy, then every 3 months for 2 years, and then every 6 months for 3 years. Follow-up includes a physical examination, blood tests and magnetic resonance imaging of the brain.

Conditions

High Grade Gliomas; Brain Tumors

Keywords

Chemotherapy; Radiation; Brain Tumor; GBM; Radiosensitizer; Glioblastoma; Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (5)

• Median Progression Free Survival.

  Progression free survival is the interval from initiation of treatment on protocol to symptomatic or radiographic progression. Progressive disease is a \>25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.

  up to 51 months

• Percentage of Participants With Progression Free Survival at 6, 12, and 24 Months

  Percentage of participants who were progression free by 6, 12, or 24 months. Progressive disease is a \>25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.

  6, 12, and 24 months

• Number of Participants With Best Response

  Best response recorded from the start of treatment until disease progression/recurrence. Complete response is complete resolution of all contrast enhancing tumor documented at initiation of treatment on protocol, with no appearance of new lesions. Partial response is a \>50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Minor response is a \>25%, but \<50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Stable disease is a change in tumor size less than MR but not demonstrating progressive disease. Progressive disease is a \>25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol. Not evaluable means the participant cannot be evaluated (e.g., quality of scan).

  up to 63.8 months

• Median Overall Survival

  Survival is the interval from the initiation of treatment on protocol to date of death.

  up to 63.8 months

• Percentage of Participants With Overall Survival at 6, 12, and 24 Months

  Percentage of participants who were alive at 6, 12, and 24 months.

  6, 12, and 24 months

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  6 years, 7 months and 27 days

Study Arms (1)

Valproic Acid

EXPERIMENTAL

Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.

Procedure: adjuvant therapy; Drug: Temozolomide; Drug: Valproic Acid; Radiation: Radiation therapy

Interventions

adjuvant therapy PROCEDURE

Valproic Acid

Temozolomide DRUG

Orally 75mg/m\^2 first day of radiation until completion. Restart 4 weeks post radiation.

Also known as: Temodar

Valproic Acid

Valproic Acid DRUG

Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.

Also known as: Depakote

Valproic Acid

Radiation therapy RADIATION

External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.

Valproic Acid

Eligibility Criteria

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

You may qualify if:

• Histological diagnosis:
• Pathologically confirmed glioblastoma multiforme.
• Histologic diagnosis of glioblastoma multiforme (GBM) will have been established by biopsy or resection no more than 6 weeks prior to enrollment.
• The patient is a candidate for definitive external beam radiotherapy.
• Patients must be older than 18 years with a life expectancy greater than 8 weeks.
• Patients should have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Patients must have a primary medical oncologist in the community who is willing to collaborate with the Radiation Oncology Branch (ROB) staff in the clinical management of the patient, specifically in the prescription of Temozolomide and toxicity monitoring in the adjuvant phase.
• Laboratory functions:
• Adequate bone marrow function defined as a peripheral absolute granulocyte count of greater than 1500/mm\^3, hemoglobin greater than 10gm/dL, and platelet count greater than 100,000/mm\^3.
• Adequate liver function, defined as bilirubin and serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) less than 2 x the upper limit of normal.
• Serum creatinine less than 1.5 mg/dl.
• Serum albumin greater than 0.75 x normal.
• All patients or their legal guardian must sign a document of informed consent indicating their understanding of the investigational nature and the risks of this study BEFORE any of the protocol related studies are performed (this does not include routine laboratory tests or imaging studies required to establish eligibility).
• Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.

You may not qualify if:

• Prior therapy:
• Patients who have previously received valproic acid.
• Patients who have previously received radiation therapy to the brain.
• Patients who have received chemotherapy for the treatment of their high grade glioma or who are currently receiving other investigational chemotherapeutic agents.
• Patients with a known history of disorders of urea metabolism.
• Concurrent therapy:
• The concurrent use of sulfamethoxazole, salicylates or naproxen is not allowed.
• Patients with a history of or concurrent second malignancy other than non-melanoma skin cancer or cervical cancer less than 3 years since GBM diagnosis.
• Pregnant or breast-feeding females are excluded because of the potential mutagenic effects on a developing fetus or newborn.
• Clinically significant unrelated systemic illness which in the judgement of the Principal or Associate Investigator would compromise the patient's ability to tolerate this therapy or are likely to interfere with the study procedures or results, including but not limited to Insulin dependent diabetes.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104-6056, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

Location

Related Publications (2)

• Davis FG, McCarthy BJ, Freels S, Kupelian V, Bondy ML. The conditional probability of survival of patients with primary malignant brain tumors: surveillance, epidemiology, and end results (SEER) data. Cancer. 1999 Jan 15;85(2):485-91.

  PMID: 10023719 BACKGROUND

• Loeffler JS, Alexander E 3rd, Shea WM, Wen PY, Fine HA, Kooy HM, Black PM. Radiosurgery as part of the initial management of patients with malignant gliomas. J Clin Oncol. 1992 Sep;10(9):1379-85. doi: 10.1200/JCO.1992.10.9.1379.

  PMID: 1325539 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Brain Neoplasms; Glioblastoma

Interventions

Chemotherapy, Adjuvant; Temozolomide; Valproic Acid; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Fatty Acids; Lipids

Results Point of Contact

• Title: Kevin Camphausen, M.D.
• Organization: National Cancer Institute, national Institutes of Health

camphauk@mail.nih.gov

301-496-5457

Study Officials

• Kevin A Camphausen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 11, 2006
• First Posted: March 13, 2006
• Study Start: March 1, 2006
• Primary Completion: June 1, 2013
• Study Completion: November 1, 2014
• Last Updated: August 18, 2016
• Results First Posted: June 24, 2014

Record last verified: 2016-07

Locations

US (3)