Study of IDO Inhibitor and Temozolomide for Adult Patients With Primary Malignant Brain Tumors
Glioblastoma Multiforme - Glioma - Gliosarcoma - Malignant Brain Tumor
Conditions: official terms
Astrocytoma - Brain Neoplasms - Glioblastoma - Gliosarcoma
Conditions: Keywords
glioblastoma multiforme, glioma, gliosarcoma, malignant brain tumor
Study Type
Study Phase
Phase 1/Phase 2
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: Indoximod Type: Drug
Name: Temozolomide Type: Drug
Overall Status
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 with 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).
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 70 Years
Minimum Age: 16 Years
Gender: Both
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. There must be imaging confirmation (with and without gadolinium contrast) of tumor progression or regrowth.

- 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.

- Patients must have completed a course of radiation therapy and at least 2 adjuvant cycles of temozolomide for the phase 2 component.

- Prior temozolomide is not required for the phase 1 component; prior radiation is required for the phase 1 arm. It is suggested (but not required) that patients be at least 3 months post radiation to reduce the chances of pseudoprogression.

- Patients must be on a steroid dose less than 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 and 70

- Normal organ functions, which includes adequate: Bone marrow function as defined by the following laboratory values:

- Absolute Neutrophil Count (ANC) ≥ 1.0 x 10^9/L

- Platelets ≥ 100 x 10^9/L

- Hemoglobin ≥ 9.0 g/dL

- Renal function (creatinine level within normal institutional limit, or creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal).

- Liver function (AST/ALT ≤2.5 X institutional upper limit of normal, Total bilirubin ≤ 1.5 times ULN, INR within 1.5 times ULN (or if receiving anticoagulant therapy an INR of ≤ 3.0 is allowed with concomitant increase in PT or an aPTT ≤ 2.5 × control).

- Must be 28 days from the administration of any investigational agent or prior cytotoxic therapy with the following exceptions:

o 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.).

- Patients with prior therapy that included interstitial brachytherapy, Gliadel wafer, or stereotactic radiosurgery must have confirmation of progressive disease, rather than radiation necrosis, by PET scanning, Thallium scanning, MRI spectroscopy, or surgical documentation.

- The effects of indoximod on the developing human fetus are unknown. For this reason and because indoximod may affect maternal immune tolerance of the fetus, sexually active women of child-bearing potential must agree to use two forms of contraception (hormonal and barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Use of contraception or abstinence should continue for a minimum of 1 month after completion of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should discontinue the study drug and inform her treating physician immediately. Also men should be discouraged from fathering children while on treatment.

- Life expectancy greater than 6 months.

Exclusion Criteria:

- Prior invasive malignancy that is not the 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.

- Active systemic infection requiring treatment, including any HIV infection or toxoplasmosis.

- Systemic corticosteroid therapy > 2 mg of dexamethasone daily (or equivalent) at study enrollment.

- Patients with significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol must have a legally authorized representative (LAR) willing to participate and support the patient throughout the trial. Affected patients without a LAR are excluded from participation.

- Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.

- Active or history of autoimmune disease

- Pregnant women are excluded from this study, where pregnancy is confirmed by a positive serum hCG laboratory test (> 5 mIU/mL); breastfeeding should be discontinued.

- Patients with known autoimmune thyroid disease or positive anti-TPO antibodies (anti-Thyroid Peroxidase) at time of screening.
Moffitt Cancer Center
Tampa, Florida, United States
Status: Recruiting
Contact: Stephan Bart - 813-745-1689 -
University Cancer and Blood Center
Athens, Georgia, United States
Status: Recruiting
Contact: Jamie Hodgson, CCRC - 706-353-2990
Georgia Regents University
Augusta, Georgia, United States
Status: Recruiting
Contact: Christine Sanchez, RN - 706-721-0660 -
University of Chicago
Chicago, Illinois, United States
Status: Recruiting
Contact: Jennifer Nam - 773-702-7716 -
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Status: Recruiting
Contact: Melanie Frees, RN, BSN, CCRC - 319-356-1228 -
John Nasseff Neuroscience Institute
Minneapolis, Minnesota, United States
Status: Recruiting
Contact: Amy Schrecengost, BS, CCRC - 612-863-6562 -
Huntsman Cancer Center
Salt Lake City, Utah, United States
Status: Recruiting
Contact: Karthik Sonty - 801-587-5562 -
Virginia Cancer Specialists
Fairfax, Virginia, United States
Status: Recruiting
Contact: Noel Swafford - 703-208-3192 -
Start Date
March 2014
NewLink Genetics Corporation
NewLink Genetics Corporation
Record processing date processed this data on July 28, 2015 page