NCT00437957

Phase I Trial Of Temozolomide Combined With The Histone Deacetylase Inhibitor Valproic Acid (VPA) And Whole Brain Radiation Therapy (WBR) For Brain Metastases From Solid Tumors In Adults

Terminated Phase 1 Last updated 20 February 2017

What this trial tests

Phase 1 trial testing Temozolomide in Brain Metastases in 10 participants. Terminated before completion.

Timeline

1 December 2006

Primary endpoint
1 April 2009

1 April 2009

Quick facts

Lead sponsor	H. Lee Moffitt Cancer Center and Research Institute
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	1 December 2006
Primary completion	1 April 2009
Estimated completion	1 April 2009
Sites	1 location across United States

Drugs / interventions tested

• Temozolomide (temozolomide) — full drug profile →
• Valproic Acid (valproic acid) — full drug profile →
• Whole Brain Radiation Therapy

Conditions studied

• Brain Metastases — all drugs for Brain Metastases →

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Who can join

18 and older, any sex, with Brain Metastases. 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.

• Safety and tolerability of temozolomide in combination with VPA and Whole-Brain Radiation
  Time frame: approximately 74 days per patient
• Determination of the MTD of VPA in combination with temozolomide and Whole-Brain Radiation
  Time frame: approximately 74 days per patient

Sponsor's own description

This type of study is called a "Phase I study". Its purpose is to determine the side effects of the two medicines listed in this study when given together with whole brain radiation, and the highest dose of valproic acid that can be given together with temozolomide and whole brain radiation. We will also study the drug combination's effectiveness in treating cancer. While both of these drugs and whole brain radiation have been used in people for many years, they have never been combined for the purpose of treating patients with cancer.

Publications & conference data

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

1. Trials with 'epigenetic' drugs: an update.
   Nebbioso A, Carafa V, Benedetti R, Altucci L. · · 2012 · cited 162× · PMID 23103179 · DOI 10.1016/j.molonc.2012.09.004
2. 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
3. Epigenetic Targeted Therapy for Diffuse Intrinsic Pontine Glioma.
   Hashizume R. · · 2017 · cited 32× · PMID 28592748 · DOI 10.2176/nmc.ra.2017-0018
4. Epigenetic modification in chromatin machinery and its deregulation in pediatric brain tumors: Insight into epigenetic therapies.
   Maury E, Hashizume R. · · 2017 · cited 30× · PMID 28059591 · DOI 10.1080/15592294.2016.1278095
5. Chromatin Modulation by Histone Deacetylase Inhibitors: Impact on Cellular Sensitivity to Ionizing Radiation.
   Carrier F. · · 2013 · cited 21× · PMID 24648865
6. Valproic acid promotes radiosensitization in meningioma stem-like cells.
   Chiou HY, Lai WK, Huang LC, Huang SM, et al · · 2015 · cited 16× · PMID 25895030 · DOI 10.18632/oncotarget.3692
7. Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.
   Zhang Y, Wu L, Wang Z, Wang J, et al · · 2022 · cited 11× · PMID 35875060 · DOI 10.3389/fonc.2022.838637
8. Relevance of humanized three-dimensional tumor tissue models: a descriptive systematic literature review.
   Contartese D, Salamanna F, Veronesi F, Fini M. · · 2020 · cited 6× · PMID 32285137 · DOI 10.1007/s00018-020-03513-y