Clinical trial NCT02052648: Study of IDO Inhibitor and Temozolomide for Adult Patients With Primary Malignant Brain Tumors
Official title: A Phase I/II Study of the Combination of Indoximod and Temozolomide for Adult Patients With Temozolomide-Refractory Primary Malignant Brain Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Glioblastoma Multiforme
Glioma
Gliosarcoma
Malignant Brain Tumor
Keywords: glioblastoma multiforme
glioma
gliosarcoma
malignant brain tumor
Lead sponsor: Lumos Pharma
Sponsor class: INDUSTRY
First posted: 2014-02-03
Enrollment: 160
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: Inclusion Criteria:

* 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.).

Exclusion Criteria:

* 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

Primary outcomes:
measure: Frequency of Regimen-Limiting Toxicities (RLTs) in Phase 1 Subjects
timeFrame: 3 months
measure: Phase 2: Number of Phase 1 Participants With Efficacy Outcomes
timeFrame: 6 months
Secondary outcomes:
measure: Overall Response Rate for Phase 2 Participants
timeFrame: 18 months
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: 18 Months
Other outcomes:
Locations:
city: Castro Valley
country: United States
facility: Eden Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: UC Irvine Chao Family Comprehensive Cancer Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Athens
country: United States
facility: University Cancer and Blood Center
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucy
state: Kentucky
city: Minneapolis
country: United States
facility: John Nasseff Neuroscience Institute
state: Minnesota
city: Albuquerque
country: United States
facility: University of New Mexico Comprehensive Cancer Center
state: New Mexico
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health Comprehensive Cancer Center
state: North Carolina
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Austin
country: United States
facility: Texas Oncology
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Center
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
Study officials:
References: