Study of IDO Inhibitor and Temozolomide for Adult Patients With Primary Malignant Brain Tumors
In this study, investigators will conduct a phase I/II trial in recurrent (temozolomide resistant) glioma patients. The overall goal of this study is to provide a foundation for future studies with indoximod tested in newly diagnosed glioblastoma patients with radiation and temozolomide, or in combination with vaccine therapies.
Malignant Brain Tumor
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of the Combination of Indoximod and Temozolomide for Adult Patients With Temozolomide-Refractory Primary Malignant Brain Tumors|
- Phase 2 Dosing [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
Phase 1b component:
Primary objective is to determine the recommended Phase 2 dose of indoximod and temozolomide in combination for treatment of progressive high-grade glioma (including glioblastoma multiforme) or gliosarcoma.
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Phase 1b component:
To determine the adverse event profile (event type, incidence severity, duration causality and treatment intervention) and identify regimen-limiting toxicities (RLT) of indoximod plus temozolomide in combination therapy.
Specifically, investigators define regimen-limiting toxicity (RLT) as a toxicity that delays the planned administration of the next cycle of the backbone chemotherapy. The goal of the trial will be to find the maximum dose of indoximod that does not induce RLT in more than 1/6 of patients treated with temozolomide.
- Overall Dose of Temozolomide Delivered Versus Historical Control [ Time Frame: 1 year ] [ Designated as safety issue: No ]To test the hypothesis that the addition of indoximod will not reduce the overall dose of temozolomide delivered or delay the timing of administration, compared to historical controls using T-test.
- Pharmacokinetics [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Phase 1b component:
To determine the pharmacokinetic profile of indoximod in the setting of this treatment regimen. A thorough pharmacokinetic (PK) profile will be performed for each patient entered into the study through analysis of blood samples collected at protocol-defined time points.
|Study Start Date:||March 2014|
|Estimated Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Experimental: Phase 1b Cohort 1
Phase 1B patients will receive Indoximod given in escalating doses. Initial dosing will be 600 mg BID by mouth with escalation planned to 1200 mg BID by mouth. The medication should be taken twice daily for 28 days each cycle.
Temozolomide will also be given by mouth at 150 mg/m^2 x 5 days at all dosing levels of indoximod. Each cycle is 28 days. Patients will continue until they experience disease progression or toxicity.
Indoximod will be administered in escalating doses. Initial dosing will be 600 mg BID by mouth with escalation planned to 1200 mg BID by mouth
Indoximod in the form of 200 mg capsules will be given (3, 5, and 6 capsules depending on the escalated dose). Indoximod should be taken with water by mouth one hour before breakfast and one hour prior to dinner. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.
If temozolomide is discontinued due to toxicity, patients may continue to receive indoximod alone.
Phase 2 Treatment Plan (Cohort 2):
This group of patients will receive fixed doses of indoximod determined in the phase 1 part, based on tolerability.
Other Names:Drug: Temozolomide
Phase 1 portion:
Temozolomide to be given by mouth at 150 mg/m^2 x 5 days at all dosing levels of indoximod. Each cycle is 28 days. Patients will continue until they experience disease progression or toxicity.
The aim of this study is to identify the safety profile and the recommended dose for phase 2 study of the combination of indoximod (portion 1, phase 1b study). Investigators will then evaluate the tolerability and the preliminary activity in patients with recurrent GBM in three different situations:
- Combination of indoximod and temozolomide (bevacizumab-naive patients)
- Combination of indoximod and temozolomide with bevacizumab
- Combination of indoximod and temozolomide with stereotactic radiation. Ancillary studies will be conducted to assess the correlation between intra-tumoral IDO expression or serum biomarkers (immune monitoring) and treatment efficacy.
If the current study shows an acceptable safety profile and suggests preliminary evidence of activity, this will provide the justification for subsequent randomized phase 2 studies in refractory glioblastoma multiforme (GBM).
Please refer to this study by its ClinicalTrials.gov identifier: NCT02052648
|United States, Georgia|
|Georgia Regents University||Recruiting|
|Augusta, Georgia, United States, 30912|
|Contact: Christine Sanchez, RN 706-721-0660 email@example.com|
|Principal Investigator: Samir Khleif, MD|
|Study Director:||Nicholas Vahanian, MD||NewLink Genetics Corporation|