Clinical Trial: Study of Vismodegib in Combination With Temozolomide Versus Temozolomide Alone in Patients With Medulloblastomas With an Activation of the Sonic Hedgehog Pathway
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: An International, Randomized, Open-label Phase I/II Study of Vismodegib in Combination With Temozolomide Versus Temozolomide Alone in Adult Patients With Recurrent or Refractory
Brief Summary:
The purpose of this study is to evaluate the safety of vismodegib in combination with temozolomide (primary objective - phase I) and to estimate the efficacy of vismodegib in combination with temozolomide in adult patients with recurrent, progressive, or refractory medulloblastomas to standard therapy measured by the 6-month progression-free rate (phase II).
This study is an open-label Phase I/II, international, randomized.
38 patients will be included in the study.
Detailed Summary:
Secondary objectives are :
phase I : to collect preliminary results on the 6-month progression-free rate of the combination vismodegib + temozolomide
PHASE II
To estimate in the two study arms:
- the objective response rate (Complete response + Partial Response according to WHO criteria) after 6 months of treatment
- the duration of treatment response
- the best overall response obtained during the study
- the progression-free survival (PFS)
- the time to progression (TTP)
- the time to treatment failure (TTF)
- In the combination arm (vismodegib + temozolomide): to further evaluate the safety of the combination.
Sponsor: Centre Leon Berard
Current Primary Outcome:
- To evaluate the safety of a fixed dose of vismodegib in combination with (phase I)temozolomide in adult patients with recurrent, progressive, or refractory to standard therapy medulloblastoma [ Time Frame: during the first three months follow up ]
number of severe toxicities occurring during the first 3 months of follow-up :
- Toxic death
- Grade 4 toxicity
- Any grade 3 AE leading to study treatment interruption for more than 7 days or discontinuation.
- To estimate the efficacy of vismodegib in combination with temozolomide in adult patients with recurrent, progressive, or refractory to standard therapy medulloblastoma (phase II) [ Time Frame: 6 months after start of treatment ]the 6-month progression-free rate
Original Primary Outcome: Same as current
Current Secondary Outcome:
- To collect preliminary results on the 6-month progression-free rate of the combination vismodegib + temozolomide (phase I) [ Time Frame: 6 months after start of treatment ]measurement of progression free rate
- To estimate in the two study arms the objective response rate after 6 months of treatment (phase II) [ Time Frame: after 6 months of treatment ]measure by objective response rate
- To estimate in the two study arms the duration of treatment response (phase II) [ Time Frame: one year ]treatment response
- To estimate in the two study arms the best overall response obtained during the study (phase II) [ Time Frame: one year ]
- To estimate in the two study arms the progression-free survival (PFS)(phase II) [ Time Frame: one year ]measure of progression free rate
- To estimate in the two study arms the time to treatment failure (phase II) [ Time Frame: one year ]
- frequency of adverse events based on the common toxicity criteria (CTC-AE-V4.0) grade [ Time Frame: one year ]In the combination arm (vismodegib + temozolomide): to further evaluate the safety of the combination
Original Secondary Outcome:
- To collect preliminary results on the 6-month progression-free rate of the combination vismodegib + temozolomide (phase I) [ Time Frame: 6 months after start of treatment ]measurement of progression free rate
- To estimate in the two study arms the objective response rate after 6 months of treatment (phase II) [ Time Frame: after 6 months of tratment ]measure by objective response rate
- To estimate in the two study arms the duration of treatment response (phase II) [ Time Frame: one year ]treatment response
- To estimate in the two study arms the best overall response obtained during the study (phase II) [ Time Frame: one year ]
- To estimate in the two study arms the progression-free survival (PFS)(phase II) [ Time Frame: one year ]measure of progression free rate
- To estimate in the two study arms the time to treatment failure (phase II) [ Time Frame: one year ]
- frequency of adverse events based on the common toxicity criteria (CTC-AE-V4.0) grade [ Time Frame: one year ]In the combination arm (vismodegib + temozolomide): to further evaluate the safety of the combination
Information By: Centre Leon Berard
Dates:
Date Received: May 15, 2012
Date Started: June 2012
Date Completion: October 2018
Last Updated: October 31, 2016
Last Verified: October 2016