NCT00302159

A Phase II Clinical Trial of the Histone Deacetylase Inhibitor Valproic Acid in Combination With Temodar and Radiation Therapy in Patients With High Grade Gliomas: Multi-Institutional Trial

Completed Phase 2 Results posted Last updated 19 July 2016

What this trial tests

Phase 2 trial testing adjuvant therapy in High Grade Gliomas in 43 participants. Completed in 1 November 2014.

Timeline

1 March 2006

Primary endpoint
1 June 2013

1 November 2014

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	43
Start date	1 March 2006
Primary completion	1 June 2013
Estimated completion	1 November 2014
Sites	3 locations across United States

Drugs / interventions tested

• adjuvant therapy — full drug profile →
• Temozolomide (temozolomide) — full drug profile →
• Valproic Acid (valproic acid) — full drug profile →
• Radiation therapy — full drug profile →

Conditions studied

• High Grade Gliomas — all drugs for High Grade Gliomas →
• Brain Tumors — all drugs for Brain Tumors →

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 90, any sex, with High Grade Gliomas or Brain Tumors. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Median Progression Free Survival.
  Time frame: up to 51 months
  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.
• Percentage of Participants With Progression Free Survival at 6, 12, and 24 Months
  Time frame: 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.
• Number of Participants With Best Response
  Time frame: up to 63.8 months
  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
• Median Overall Survival
  Time frame: up to 63.8 months
  Survival is the interval from the initiation of treatment on protocol to date of death.
• Percentage of Participants With Overall Survival at 6, 12, and 24 Months
  Time frame: 6, 12, and 24 months
  Percentage of participants who were alive at 6, 12, and 24 months.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.
   Cheng Y, He C, Wang M, Ma X, et al · · 2019 · cited 760× · PMID 31871779 · DOI 10.1038/s41392-019-0095-0
2. Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi.
   Suraweera A, O'Byrne KJ, Richard DJ. · · 2018 · cited 496× · PMID 29651407 · DOI 10.3389/fonc.2018.00092
3. Histone Deacetylases Inhibitors in Neurodegenerative Diseases, Neuroprotection and Neuronal Differentiation.
   Shukla S, Tekwani BL. · · 2020 · cited 211× · PMID 32390854 · DOI 10.3389/fphar.2020.00537
4. Histone deacetylase inhibitors as radiosensitisers: effects on DNA damage signalling and repair.
   Groselj B, Sharma NL, Hamdy FC, Kerr M, et al · · 2013 · cited 146× · PMID 23361058 · DOI 10.1038/bjc.2013.21
5. Radioresistance in Glioblastoma and the Development of Radiosensitizers.
   Ali MY, Oliva CR, Noman ASM, Allen BG, et al · · 2020 · cited 128× · PMID 32899427 · DOI 10.3390/cancers12092511
6. Valproic acid use during radiation therapy for glioblastoma associated with improved survival.
   Barker CA, Bishop AJ, Chang M, Beal K, et al · · 2013 · cited 102× · PMID 23523186 · DOI 10.1016/j.ijrobp.2013.02.012
7. The application of histone deacetylases inhibitors in glioblastoma.
   Chen R, Zhang M, Zhou Y, Guo W, et al · · 2020 · cited 93× · PMID 32682428 · DOI 10.1186/s13046-020-01643-6
8. The challenges and the promise of molecular targeted therapy in malignant gliomas.
   Wang H, Xu T, Jiang Y, Xu H, et al · · 2015 · cited 92× · PMID 25810009 · DOI 10.1016/j.neo.2015.02.002