The purpose of this research study is to test the safety, tolerability, and effectiveness of the combination of three drugs, sorafenib (Nexavar®), valproic acid (Depakote®), and sildenafil (Viagra®), when used to treat high-grade glioma, a type of brain tumor.
The study is a single-center, open-label phase 2 study, with an early stopping rule in place for safety. The trial will include patients with recurrent or progressive high-grade glioma. The trial will be conducted in an adaptive design, with a Simon's mini-max 2-stage design incorporating an interim analysis for efficacy
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
47
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States
Number of Participants With 6-Month Progression Free Survival (PFS)
Number of patients evaluable for response, regardless of tumor platelet derived growth factor receptor (PDGFR) status, with 6- month PFS defined as the time from the first day a patient receives study treatment until time of progression per response assessment in neuro-oncology (RANO) or Macdonald criteria or death, whichever occurs first.
Time frame: Up to 6 months
Number of Participants Whose Tumors Express PDGFRa With and Without 6-Month PFS.
Number of patients evaluable for response, with tumors that express PDGFRα, with 6-month PFS defined as the time from the first day a patient receives study treatment until time of progression per RANO or Macdonald criteria or death, whichever occurs first.
Time frame: Up to 6 months
Number of Participants With Best Response of CR Plus Number of Participants With Best Response of PR.
Overall response rate (CR+PR), using RANO or Macdonald criteria, in patients evaluable for response regardless of tumor PDGFR status
Time frame: From the first day of study treatment until best response or off study, up to 4 years
Number of Participants Whose Tumors Express PDGFRa With Best Response of CR Plus Number of Participants Whose Tumor Expresses PDGFRa With Best Response of PR.
Overall response rate (CR+PR), using RANO or Macdonald criteria, in patients who are evaluable for response and who have tumors that express PDGFRα.
Time frame: From initiation of study treatment to time of best response or off-study (up to 4 years)
Number of Participants With 12-Month Overall Survival (OS)
Number of patients evaluable for response, regardless of tumor PDGFR status, who are alive at 12 months after the first day a patient receives study treatment. Overall Survival (OS) defined as the time from the first day a patient receives study treatment until death by any cause.
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Time frame: 12 months
Number of Participants Whose Tumors Express PDGFRa With and Without 12-Month OS.
Number of patients evaluable for response with tumors that express PDGFRα who are alive at 12 months after the first day a patient receives study treatment. On study is defined as the time from the first day a patient receives study treatment until death by any cause.
Time frame: Up to 12 months
Evaluation of Safety and Toxicity of Sorafenib, Valproic Acid, and Sildenafil
Number of patients with adverse events
Time frame: From initiation of study therapy to completion of adverse event (AE) observation period, up to 30 days following the end of study treatment, up to 7 years.