Malignant Glioma (WHO Grade III or IV) Clinical Trial
Official title:
A Phase 1/2 Unblinded Trial of Carboxyamidotriazole Orotate (CTO) Alone or in Combination With Lomustine for Bevacizumab-Naïve Adult Patients With Recurrent Malignant Glioma
This is a Phase 1/2 study of the combination of CTO with lomustine in patients with
recurrent malignant glioma to be treated at the Preston Robert Tisch Brain Tumor Center
(PRTBTC) at Duke. The Primary Objectives are:
- Phase 1: To determine the maximum tolerated dose (MTD) of CTO when combined with
lomustine among patients with recurrent malignant glioma (World Health Organization
(WHO) grade III or IV) who have not been previously treated with bevacizumab.
- Phase 2: To assess the efficacy of CTO (either in monotherapy or in combination with
lomustine) compared to lomustine alone in patients with recurrent WHO grade IV
malignant gliomas that have not been previously treated with bevacizumab based upon
6-month progression free survival (PFS6).
Note: This study was terminated early due to funding issues. At the time of termination, the
study was still in Phase 1 and no MTD for the combination of CTO and lomustine had been
determined for this population. Phase 2 will not proceed.
In the Phase 1 component of the study, we will conduct a dose-escalation study of the
combination of CTO with lomustine among patients with recurrent malignant glioma (WHO grade
III or IV). All patients will be bevacizumab-naïve. The dose escalation will be a standard
"3+3" design to determine the MTD of CTO in combination with lomustine. The Phase 2 portion
of this study will be a randomized screening study comparing CTO alone (Arm A) versus CTO
with lomustine (Arm B) versus lomustine alone (Arm C) in patients with recurrent WHO grade
IV malignant glioma who are bevacizumab-naïve. Subjects will be randomized with a treatment
arm allocation ratio of 2:2:1.
Based on the results of patients who have already taken part in Phase 1 of the study, the
Principal Investigator has decided to reduce the dose of lomustine used in combination with
CTO in this study by 25% of the FDA-approved dose, due to hematologic side effects (side
effects related to lower than expected blood counts). Therefore, the dose of lomustine
received in combination with CTO is approximately 75% of the standard recommended dose.
Note: This study was terminated early due to funding issues. At the time of termination, the
study was still in Phase 1 and no MTD for the combination of CTO and lomustine had been
determined for this population. Phase 2 will not proceed.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Terminated |
NCT01954030 -
Phase 1/2 CTO + Bevacizumab for Recurrent Glioma Post-Bevacizumab Failure
|
Phase 1 |