Clinical Trial: Sorafenib Tosylate, Valproic Acid, and Sildenafil Citrate in Treating Patients With Recurrent High-Grade Glioma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase II Study of Sorafenib, Valproic Acid, and Sildenafil in the Treatment of Recurrent High-Grade Glioma

Brief Summary: This phase II trial studies how well sorafenib tosylate, valproic acid, and sildenafil citrate works in treating patients with recurrent high-grade glioma. Sorafenib tosylate, valproic acid, and sildenafil citrate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Summary: The combination of sorafenib, valproic acid, and sildenafil may have therapeutic potential for the treatment of recurrent high-grade glioma in the clinic. The combination of sorafenib and valproic acid is predicated on the basis that sorafenib activity is enhanced by HDAC inhibition. The addition of sildenafil is based on its ability to block ABCB1 and ABCG2 drug efflux pumps. As the ABCG2 transporter is the primary transporter involved in the efflux of sorafenib at the BBB, blocking its action is predicted to increase the concentration of sorafenib in the brain.
Sponsor: Virginia Commonwealth University

Current Primary Outcome: PFS [ Time Frame: 6 months ]

The Kaplan-Meier method will be used to describe the time to progression and the median time to progression will be estimated, along with its 95% confidence intervals, for the entire population and for PDGFRa expression, respectively. Cox regression analysis will be used to evaluate baseline characteristics and any potential covariates.


Original Primary Outcome: Determine the efficacy of the combination of sorafenib, valproic acid, and sildenafil, in terms of 6-month PFS in GBM [ Time Frame: 6 months ]

The primary endpoint is whether a patient has a 6-month PFS or not. The proportion of patients who have 6-month PFS in the entire cohort and in PDGFRα expressing tumor and their confidence intervals will be calculated, respectively. The Kaplan-Meier method will be used to describe the time to progression and the median time to progression will be estimated, along with its 95% confidence intervals (23), for the entire population and for PDGFRα expression, respectively. Cox regression analysis will be used to evaluate baseline characteristics and any potential covariates.


Current Secondary Outcome:

  • Overall best response rate (complete response + partial response) using RANO or Macdonald criteria. [ Time Frame: Up to 4 years ]
    Will be estimated for the entire study population and for the PDGFRa expressing high-grade glioma cohort, along with the 95% confidence intervals.
  • Overall survival [ Time Frame: From the first day of study treatment until death by any cause, assessed up to 12 months ]
    The Kaplan-Meier method will be used to describe the time to overall survival and the median time to overall survival will be estimated, and along with its 95% confidence intervals, for the entire population and for PDGFRa expression, respectively. Cox regression analysis will be used to evaluate baseline characteristics and any potential covariates.


Original Secondary Outcome: Evaluate the overall response rate, based on Response Assessment in Neuro-Oncology (RANO) criteria, to the drug combination in the entire study population. [ Time Frame: 12 months ]

The overall best response rate to the drug combination will be estimated for the entire study population and for the PDGFRα expressing GBM cohort, along with the 95% confidence intervals.

The Kaplan-Meier method will be used to describe the time to overall survival and the median time to overall survival will be estimated, and along with its 95% confidence intervals, for the entire population and for PDGFRα expression, respectively. Cox regression analysis will be used to evaluate baseline characteristics and any potential covariates.



Information By: Virginia Commonwealth University

Dates:
Date Received: March 20, 2013
Date Started: April 11, 2013
Date Completion: December 31, 2018
Last Updated: May 3, 2017
Last Verified: May 2017