Study of IDO Inhibitor and Temozolomide for Adult Patients With Primary Malignant Brain Tumors
A Phase I/II Study of the Combination of Indoximod and Temozolomide for Adult Patients With Temozolomide-Refractory Primary Malignant Brain Tumors
1 other identifier
interventional
160
1 country
17
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2014
Longer than P75 for phase_1
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 29, 2014
CompletedFirst Posted
Study publicly available on registry
February 3, 2014
CompletedStudy Start
First participant enrolled
March 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 18, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
June 20, 2019
CompletedResults Posted
Study results publicly available
March 27, 2024
CompletedMarch 27, 2024
February 1, 2024
4.1 years
January 29, 2014
October 16, 2023
February 28, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Frequency of Regimen-Limiting Toxicities (RLTs) in Phase 1 Subjects
Number of RLTs observed in each dose level.
3 months
Phase 2: Number of Phase 1 Participants With Efficacy Outcomes
Six-month progression-free survival.
6 months
Secondary Outcomes (2)
Overall Response Rate for Phase 2 Participants
18 months
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
18 Months
Study Arms (4)
Phase 1b Cohort 1
EXPERIMENTALPhase 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.
Cohort 2a
EXPERIMENTALBevacizumab naïve phase II patients who will receive indoximod with temozolomide. Indoximod will be dosed at 1200mg BID. Temozolomide will be dosed at 150 mg/m2 and may be escalated up to 200 mg/m2.
Cohort 2b
EXPERIMENTALPhase II patients who will receive indoximod with temozolomide and bevacizumab who have previously been treated with bevacizumab. Indoximod will be dosed at 1200mg BID. Temozolomide will be dosed at 150 mg/m2 and may be escalated up to 200 mg/m2. Bevacizumab will be dosed at 10mg/kg.
Cohort 2c
EXPERIMENTALPhase II patients who will receive indoximod with temozolomide and stereotactic radiosurgery. Indoximod will be dosed at 1200mg BID. Temozolomide will be dosed at 150 mg/m2 and may be escalated up to 200 mg/m2. Single fraction SRS dose will be 16 or 20 Gy depending on target volume. The total 5-fraction SRT dose will be 27.5 Gy.
Interventions
Eligibility Criteria
You may qualify if:
- Histologically proven intracranial glioblastoma multiforme (WHO grade IV glioma) or gliosarcoma. In addition, the Phase 1b cohort will include patients with progressive WHO grade III glioma.
- Patients will be eligible if the original histology was lower grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made.
- Unequivocal radiographic evidence for tumor progression by MRI. It is understood that some patients may be resected prior to enrolling onto protocol
- Patients must have completed a course of radiation therapy and at least 2 adjuvant cycles of temozolomide for the phase 2 component.
- Patients enrolling onto Cohort 2b who have been taken off bevacizumab must have had at least a 28 day washout from any previous administration of bevacizumab. It is preferred that patients who fail bevacizumab prior to trial entry remain on bevacizumab in the trial.
- Prior temozolomide is not required for the phase 1 component; prior radiation is required for the phase 1 arm.
- Patients must be on a steroid dose less than or equal to 2 mg of dexamethasone daily (or equivalent), and this dose must not have increased for at least 14 days prior to obtaining the enrollment.
- ECOG performance status ≤1 or Karnofsky ≥70%.
- Age between 16
- Must be 28 days from the administration of any investigational agent or prior cytotoxic therapy with the following exceptions:
- Must be 14 days from administration of non-cytotoxic agents (e.g., bevacizumab (except COHORT 2b), interferon, tamoxifen, thalidomide, cis-retinoic acid, tyrosine kinase inhibitor, etc.).
You may not qualify if:
- Prior invasive malignancy that is not low-grade glioma, high-grade glioma, glioblastoma, or gliosarcoma (except non-melanomatous skin cancer or carcinoma in situ of the cervix) unless the patient has been disease free and off therapy for that disease for a minimum of 3 years.
- Patients on the phase 2 portion of the study may not have more than 2 prior regimens for recurrent disease for glioblastoma/gliosarcoma. Patients on the phase 1 portion of the study may not have had more than 3 prior regimens.
- Systemic corticosteroid therapy \> 2 mg of dexamethasone daily (or equivalent) at study enrollment.
- Active or history of autoimmune disease
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
Eden Medical Center
Castro Valley, California, 94546, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
UC Irvine Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
University Cancer and Blood Center
Athens, Georgia, 30607, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, 30342, United States
Augusta University
Augusta, Georgia, 30912, United States
University of Chicago
Chicago, Illinois, 60637, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
University of Kentucy
Lexington, Kentucky, 40536, United States
John Nasseff Neuroscience Institute
Minneapolis, Minnesota, 55407, United States
University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, 87131, United States
Wake Forest Baptist Health Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157, United States
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Texas Oncology
Austin, Texas, 78705, United States
Huntsman Cancer Center
Salt Lake City, Utah, 84112, United States
Virginia Cancer Specialists
Fairfax, Virginia, 22031, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Lumos Pharma, Inc.
- Organization
- Lumos Pharma Corporation
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 29, 2014
First Posted
February 3, 2014
Study Start
March 1, 2014
Primary Completion
April 18, 2018
Study Completion
June 20, 2019
Last Updated
March 27, 2024
Results First Posted
March 27, 2024
Record last verified: 2024-02