Clinical Trial: Ph II SAHA and Bevacizumab for Recurrent Malignant Glioma Patients

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase II Study of Bevacizumab and Vorinostat for Recurrent WHO Grade IV Malignant Glioma Patients

Brief Summary: It has been shown that bevacizumab has significant anti-tumor activity in patients with recurrent glioblastoma multiforme. Vorinostat has modest anti-tumor activity against malignant glioma and can enhance the action of both chemotherapy and anti-angiogenics. Patients will be treated with a combination of bevacizumab and vorinostat.

Detailed Summary: There is no effective therapy for patients with recurrent glioblastoma multiforme (GBM) hence such patients remain a major unmet need in oncology. The investigators have recently demonstrated that bevacizumab (BV), a humanized monoclonal antibody against vascular endothelial growth factor, has significant anti-tumor activity among recurrent glioblastoma multiforme patients. Vorinostat has modest anti-tumor activity against malignant glioma and can potentiate the action of both chemotherapy and anti-angiogenics. The current study is designed to evaluate the anti-tumor activity of vorinostat when combined with BV among recurrent glioblastoma multiforme patients.
Sponsor: Duke University

Current Primary Outcome: Six-month Progression-free Survival (PFS6) [ Time Frame: 6 months ]

The percentage of participants alive and progression-free at 6 months after the start of study treatment will be determined. Based on Response Assessment in Neuro-Oncology (RANO) criteria, progression is defined as a ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions; significant increase in T2/FLAIR; any new lesion; clear clinical deterioration not attributable to other causes apart from the tumor; failure to return for evaluation as a result of death or deteriorating condition; or clear progression of non-measurable disease. PFS6 will be calculated from the date study treatment started until the date of progression or death, or the date of last follow-up if participants are alive without progression. Kaplan-Meier methods will be used to estimate survival.


Original Primary Outcome: 6-month progression-free survival [ Time Frame: 6 months ]

Current Secondary Outcome:

  • Radiographic Response [ Time Frame: 3 Years ]
    The percentage of participants with a complete or partial response as determined by modified Response Assessment in Neuro-Oncology (RANO) criteria will be determined. Complete Response (CR) is defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses) and accompanied by a stable or improving neurologic examination. Partial Response (PR) is defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids and accompanied by a stable or improving neurologic examination. Tumor assessments are done at baseline and the end of every second cycle (every 8 weeks) thereafter.
  • Percentage of Participants Who Experience Grade 3 or Greater, Treatment Related, Non-hematologic Toxicities. [ Time Frame: 2.7 Years ]
    The percentage of participants who experience grade 3 or greater, treatment-related, non-hematologic toxicities will be calculated.
  • Median Progression-free Survival (PFS) [ Time Frame: 3 Years ]
    Progression-free survival is defined as the time in months from the start of protocol treatment until the date of progression or death if death occurred before progression. If the participant is alive and progression-free, PFS will be censored at the date of last follow-up. Kaplan-Meier methods will be used to estimate progression-free survival.
  • Median Overall Survival (OS) [ Time Frame: 3 Years ]
    Overall survival is defined as the time in months from the start of protocol treatment until the date of death, or the date of last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.


Original Secondary Outcome:

  • Radiographic Response [ Time Frame: 2.5 Years ]
    MRI evaluations for assessment of radiographic response and response will be classified according to the Response Assessment in Neuro-Oncology criteria. Brain MRI will be performed prior to the initiation of every other cycle. Comparisons of objective assessments, excluding progressive disease, are based upon major changes in tumor size on the Gd-MRI scan compared to the baseline scan. Determination of progressive disease is based upon comparison to the previous scan with the smallest measurements.
  • Safety & Tolerability [ Time Frame: 2.5 Years ]
    Grade 3 or greater, treatment related, non-hematologic toxicities.
  • Median progression-free survival [ Time Frame: 2.5 Years ]
  • Overall survival [ Time Frame: 2.5 Years ]


Information By: Duke University

Dates:
Date Received: November 28, 2012
Date Started: January 2013
Date Completion:
Last Updated: January 20, 2017
Last Verified: November 2016