Study of IDO Inhibitor and Temozolomide for Adult Patients With Primary Malignant Brain Tumors

NCT ID: NCT02052648

Last Updated: 2024-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2019-06-20

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).

Conditions

Glioblastoma Multiforme; Glioma; Gliosarcoma; Malignant Brain Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Indoximod

Intervention Type: DRUG

Temozolomide

Intervention Type: DRUG

Cohort 2a

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.

Group Type: EXPERIMENTAL

Indoximod

Intervention Type: DRUG

Temozolomide

Intervention Type: DRUG

Cohort 2b

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.

Group Type: EXPERIMENTAL

Indoximod

Intervention Type: DRUG

Temozolomide

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

Cohort 2c

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.

Group Type: EXPERIMENTAL

Indoximod

Intervention Type: DRUG

Temozolomide

Intervention Type: DRUG

Stereotactic Radiation

Intervention Type: RADIATION

Interventions

Indoximod

Intervention Type: DRUG

Temozolomide

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

Stereotactic Radiation

Intervention Type: RADIATION

Other Intervention Names

1-methyl-D-tryptophan; D-1MT; Temodar; Methazolastone; Avastin; SRS or SRT

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NewLink Genetics Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Eden Medical Center

Castro Valley, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

UC Irvine Chao Family Comprehensive Cancer Center

Orange, California, United States

Moffitt Cancer Center

Tampa, Florida, United States

University Cancer and Blood Center

Athens, Georgia, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Augusta University

Augusta, Georgia, United States

University of Chicago

Chicago, Illinois, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Kentucy

Lexington, Kentucky, United States

John Nasseff Neuroscience Institute

Minneapolis, Minnesota, United States

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, United States

Wake Forest Baptist Health Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Texas Oncology

Austin, Texas, United States

Huntsman Cancer Center

Salt Lake City, Utah, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

NLG2102

Identifier Type: -

Identifier Source: org_study_id