Combination of Checkpoint Inhibition and IDO1 Inhibition Together With Standard Radiotherapy or Chemoradiotherapy in Newly Diagnosed Glioblastoma. A Phase 1 Clinical and Translational Trial

Who is this study for? Patients with newly diagnosed glioblastoma
Status: Recruiting
Location: See location...
Intervention Type: Biological, Drug, Radiation
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

This phase I trial studies the side effects of nivolumab, BMS-986205, and standard radiation therapy with or without temozolomide in treating patients with new diagnosed glioblastoma. Immunotherapy with nivolumab, may induce changes in body?s immune system and may interfere with the ability of tumor cells to grow and spread. BMS-986205 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab and BMS-986205 may work better compared to radiation therapy and temozolomide alone in treating patients with newly diagnosed glioblastoma.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No
View:

• Patients must have a newly diagnosed histologically confirmed diagnosis of any grade IV glioma with documentation of MGMT methylation status. The histological diagnosis can be obtained either from a brain biopsy or from a neurosurgical resection of the tumor

• Note: Study enrollment is to be within 5 weeks from diagnostic surgery or biopsy

• Note: Pyrosequencing to determine MGMT methylation status will be performed at Northwestern Memorial Hospital as standard of care (SOC)

• Tumor tissue specimens from the GBM surgery or biopsy for central pathology review and exploratory analysis of immunocorrelative studies, if available (no minimum requirement)

• For subjects who had undergone tumor resection, preoperative gadolinium (Gd)-magnetic resonance imaging (MRI) and immediate postoperative Gd-MRI performed within < 72 hours after surgery or biopsy is recommended. If computed tomography (CT) scans were performed perioperatively, an MRI should be performed before initiation of study treatment

• Patients must exhibit a Karnofsky performance score of >= 70%

• Stable or decreasing dose of steroids for >= 7 days prior to registration

• Note: Patients must be off of all steroids at the time of initiation of study treatment (day 1 [D#1])

• Patients must have adequate organ and bone marrow function at registration, as defined below:

• Absolute neutrophil count >= 1500/mm^3

• Platelets >= 100,000/mm^3

• Creatinine or creatinine clearance =<1.5 times upper limit of normal or >= 60 mL/min

• Hemoglobin >=10 mg/dL

• Blood transfusion allowed

• Total bilirubin =< 1.5 times upper limit of normal

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SPGT]) =< 2.5 times above upper limit of normal

• Alkaline phosphatase =< 2.5 times above upper limit of normal

• Females of child-bearing potential (FOCBP) and males must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 5 months following completion of therapy. Should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Due to the potential interaction with study drug(s), contraceptions that use hormones are not considered to be highly effective for FOCBP participants in this study.

• NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy. Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)

• Males who are sexually active with FOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment plus 7 months after the last dose of the study treatment (i.e., 90 days [duration of sperm turnover] plus the time required for nivolumab to undergo approximately 5 half-lives). In addition, male participants must be willing to refrain from sperm donation during this time. Male participants with partners who are FOCBP are required to use a condom for study duration and until end of relevant systemic exposure defined as 7 months after the end of study treatment. This criteria applies to azoospermic males as well

• FOCBP must have a negative serum pregnancy test within 14 days of registration on study and within 24 hours of beginning study treatment

• Clinically normal cardiac function without history of ischemic heart disease in the past 6 months and normal 12 lead electrocardiogram (ECG)

• Patients must have recovered from the effects of surgery, postoperative infection, and other complications before study registration

• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Locations
United States
Illinois
Northwestern University
Recruiting
Chicago
Contact Information
Primary
Study Coordinator
cancertrials@northwestern.edu
(312)695-1301
Time Frame
Start Date: August 13, 2019
Estimated Completion Date: June 1, 2023
Participants
Target number of participants: 30
Treatments
Experimental: Cohort I (radiation, temozolomide, BMS-986205, nivolumab)
RADIATION THERAPY: Patients with MGMT methylated promoter undergo radiation therapy 5 days per week (Monday-Friday) for up to 6 weeks. Patients also receive temozolomide PO QD, IDO1 inhibitor BMS-986205 PO QD, and nivolumab IV over 30 minutes every 2 weeks for up to 6 weeks in the absence of disease progression, unacceptable toxicity, withdrawal of consent, the study ends, or until Q4W dosing begins.~MAINTENANCE THERAPY: Patients receive IDO1 inhibitor BMS-986205 PO QD on days 1-28 and nivolumab IV over 30 minutes on days 1 and 15 of cycles 1-5 and on day 1 of subsequent cycles. Within 4 weeks of radiation therapy completion, patients also receive temozolomide PO QD on days 1-5 of cycles 2-6. Cycles repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Experimental: Cohort II (radiation, BMS-986205, nivolumab)
RADIATION THERAPY: Patients with MGMT unmethylated promoter undergo radiation therapy 5 days per week (Monday-Friday) for up to 6 weeks. Patients also receive IDO1 inhibitor BMS-986205 PO QD and nivolumab IV over 30 minutes every 2 weeks for up to 6 weeks in the absence of disease progression or unacceptable toxicity.~MAINTENANCE THERAPY: Patients receive IDO1 inhibitor BMS-986205 PO QD on days 1-28 and nivolumab IV over 30 minutes on days 1 and 15 of cycles 1-5 and on day 1 of subsequent cycles. Cycles repeats every 28 days for up to 2 years in the absence of disease progression, unacceptable toxicity, withdrawal of consent, the study ends, or until Q4W dosing begins.
Sponsors
Leads: Northwestern University
Collaborators: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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