Glioblastoma MultiformePhase 1/2NCT02052648
Study of IDO Inhibitor and Temozolomide for Adult Patients With Primary Malignant Brain Tumors
A Phase 1/2 study testing Indoximod, Temozolomide and Bevacizumab in people with Glioblastoma Multiforme and Glioma, run by NewLink Genetics Corporation at 17 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Glioblastoma Multiforme, Glioma, Gliosarcoma
- What is being tested?
- Indoximod, Temozolomide and Bevacizumab
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 17 sitesUnited States
- Study dates
- Mar 2014to 20 Jun 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.).
Who cannot join
- 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
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, 87131
University Cancer and Blood Center
Athens, Georgia, 30607
Children's Healthcare of Atlanta
Atlanta, Georgia, 30342
Augusta University
Augusta, Georgia, 30912
Texas Oncology
Austin, Texas, 78705
Eden Medical Center
Castro Valley, California, 94546
University of Chicago
Chicago, Illinois, 60637
Virginia Cancer Specialists
Fairfax, Virginia, 22031
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of Kentucy
Lexington, Kentucky, 40536
Cedars-Sinai Medical Center
Los Angeles, California, 90048
John Nasseff Neuroscience Institute
Minneapolis, Minnesota, 55407
UC Irvine Chao Family Comprehensive Cancer Center
Orange, California, 92868
Huntsman Cancer Center
Salt Lake City, Utah, 84112
Moffitt Cancer Center
Tampa, Florida, 33612
Wake Forest Baptist Health Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase I/II Study of the Combination of Indoximod and Temozolomide for Adult Patients With Temozolomide-Refractory 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.
Read the detailed description
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 in patients currently receiving or having received and failed 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).
- Conditions
- Glioblastoma Multiforme, Glioma, Gliosarcoma, Malignant Brain Tumor
- Being tested
- Indoximod, Temozolomide, Bevacizumab, Stereotactic Radiation
- Keywords
- glioblastoma multiforme, glioma, gliosarcoma, malignant brain tumor
- Medical subject headings
- Glioblastoma, Glioma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IndoximodDrug
Also called 1-methyl-D-tryptophan, D-1MT
TemozolomideDrug
Also called Temodar, Methazolastone
BevacizumabDrug
Also called Avastin
Stereotactic RadiationRadiation
Also called SRS or SRT
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b Cohort 1 | Experimental | 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. Receives: Drug: Indoximod; Drug: Temozolomide |
| Cohort 2a | Experimental | Bevacizumab 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. Receives: Drug: Indoximod; Drug: Temozolomide |
| Cohort 2b | Experimental | Phase 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. Receives: Drug: Indoximod; Drug: Temozolomide; Drug: Bevacizumab |
| Cohort 2c | Experimental | Phase 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. Receives: Drug: Indoximod; Drug: Temozolomide; Radiation: Stereotactic Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Regimen-Limiting Toxicities (RLTs) in Phase 1 Subjects
Number of RLTs observed in each dose level.
Measured: 3 months
Phase 2: Number of Phase 1 Participants With Efficacy Outcomes
Six-month progression-free survival.
Measured: 6 months
Secondary outcomes (2)
Overall Response Rate for Phase 2 Participants
Subjects with a complete response or partial response by RANO assessment. Overall Response Rate was only assessed in phase 2 subjects on this trial.
Measured: 18 months
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Number of subjects with at least 1 treatment emergent adverse event.
Measured: 18 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2014 (estimated)
- Study startMar 2014
- Primary completion18 Apr 2018
- Study completion20 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- NewLink Genetics Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02052648
- Sponsor's protocol ID
- NLG2102
- Status last verified
- Feb 2024
- First submitted
- 29 Jan 2014
- Last updated
- 27 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of the Combination of Indoximod and Temozolomide for Adult Patients With Temozolomide-Refractory Primary Malignant Brain Tumors
- ClinicalTrials.gov ID
- NCT02052648
- Acronym / sponsor ID
- NLG2102
- Conditions
- Glioblastoma Multiforme, Glioma, Gliosarcoma, Malignant Brain Tumor
- Keywords
- glioblastoma multiforme, glioma, gliosarcoma, malignant brain tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- NewLink Genetics CorporationIndustry (pharma, biotech, devices)
- Study start
- Mar 2014
- Primary completion
- 18 Apr 2018 (actual)
- Study completion
- 20 Jun 2019 (actual)
- First posted
- 3 Feb 2014 (estimated)
- Results
- Posted 27 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 in patients currently receiving or having received and failed 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 1b Cohort 1 | Experimental | Drug: Indoximod, Drug: TemozolomidePhase 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 | Experimental | Drug: Indoximod, Drug: TemozolomideBevacizumab 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 | Experimental | Drug: Indoximod, Drug: Temozolomide, Drug: BevacizumabPhase 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 | Experimental | Drug: Indoximod, Drug: Temozolomide, Radiation: Stereotactic RadiationPhase 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. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IndoximodAlso: 1-methyl-D-tryptophan, D-1MT | Drug | Cohort 2a, Cohort 2b, Cohort 2c, Phase 1b Cohort 1 |
| TemozolomideAlso: Temodar, Methazolastone | Drug | Cohort 2a, Cohort 2b, Cohort 2c, Phase 1b Cohort 1 |
| BevacizumabAlso: Avastin | Drug | Cohort 2b |
| Stereotactic RadiationAlso: SRS or SRT | Radiation | Cohort 2c |
Primary outcome
Frequency of Regimen-Limiting Toxicities (RLTs) in Phase 1 Subjects
Time frame: 3 months
Number of RLTs observed in each dose level.
Phase 2: Number of Phase 1 Participants With Efficacy Outcomes
Time frame: 6 months
Six-month progression-free survival.
2 secondary outcomes
Overall Response Rate for Phase 2 Participants
Time frame: 18 months
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time frame: 18 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Indoximod, Temozolomide and Bevacizumab in people with Glioblastoma Multiforme and Glioma, run by NewLink Genetics Corporation at 17 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of Regimen-Limiting Toxicities (RLTs) in Phase 1 Subjects (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2024.