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

Glioma Clinical Trial

Official title:

A Phase I/II Study of the Combination of Indoximod and Temozolomide for Adult Patients With Temozolomide-Refractory Primary Malignant Brain Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02052648
• Other study ID #: NLG2102
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2014
• Est. completion date: June 20, 2019

Study information

• Verified date: February 2024
• Source: Lumos Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 therapies.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: June 20, 2019
• Est. primary completion date: April 18, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Neoplasms
• Glioblastoma
• Glioblastoma Multiforme
• Glioma
• Gliosarcoma
• Malignant Brain Tumor

Intervention

Drug:
• Indoximod

• Temozolomide

• Bevacizumab

Radiation:
• Stereotactic Radiation

Locations

Country	Name	City	State
United States	University of New Mexico Comprehensive Cancer Center	Albuquerque	New Mexico
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	Texas Oncology	Austin	Texas
United States	Eden Medical Center	Castro Valley	California
United States	University of Chicago	Chicago	Illinois
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Kentucy	Lexington	Kentucky
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	John Nasseff Neuroscience Institute	Minneapolis	Minnesota
United States	UC Irvine Chao Family Comprehensive Cancer Center	Orange	California
United States	Huntsman Cancer Center	Salt Lake City	Utah
United States	Moffitt Cancer Center	Tampa	Florida
United States	Wake Forest Baptist Health Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
NewLink Genetics Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Regimen-Limiting Toxicities (RLTs) in Phase 1 Subjects	Number of RLTs observed in each dose level.	3 months
Primary	Phase 2: Number of Phase 1 Participants With Efficacy Outcomes	Six-month progression-free survival.	6 months
Secondary	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.	18 months
Secondary	Number of Participants With Adverse Events as a Measure of Safety and Tolerability	Number of subjects with at least 1 treatment emergent adverse event.	18 Months