INCB7839 dosing will begin at 120 mg/m2/dose BID which is equivalent to the adult RP2D (200 mg PO BID) based on a typical adult size of 1.67m2. The INCB7839 dose may be decreased to 80 mg/m2/dose BID if the staring dose is not tolerable. 28 consecutive days (4 weeks) will constitute one course. Patients may continue to receive INCB7839 for 26 courses (approximately 2 years).

Glioblastoma Multiforme

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

DIPG

High-grade Astrocytoma NOS

CNS Primary Tumor, NOS (Malignant Glioma)

INCB7839

Children's Hospital Los Angeles

Lucile Packard Children Hospital Stanford University

Children's Hospital Colorado

Children's National Medical Center

Children's Healthcare of Atlanta

Lurie Childrens Hospital-Chicago

National Cancer Institute Pediatric Oncology Branch

Dana Farber Cancer Institute

Memorial Sloan Kettering Cancer Center

Cincinnati Children Hospital Medical Center

Children Hospital of Pittsburgh of UPMC

St. Jude Children Research Hospital

Baylor College of Medicine

INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas

A Phase I Study of the Adam-10 Inhibitor, INCB7839 in Children With Recurrent/Progressive High-Grade Gliomas to Target Microenvironmental Neuroligin-3

Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0.

To estimate the maximum tolerated dose (MTD) and/or recommend Phase II dose (RP2D) of INCB7839 administered orally in children with recurrent/progressive high-grade glioma.

The area under the curve (AUC) will be calculated based on the course 1 days 1 and 2 pharmacokinetic samples.

The maximum concentration [CMAX] will be calculated based on the course 1 days 1 and 2 pharmacokinetic samples.

The apparent oral clearance [CL/F] will be calculated based on the course 1 days 1 and 2 pharmacokinetic samples.

The time to reach CMAX [TMAX] will be calculated based on the course 1 days 1 and 2 pharmacokinetic samples.

The progression-free survival will be reported.

The duration of response will be reported.

HER2 extracellular domain in serum will be reported.

Neuroligin-3 (NLGN3) in cerebral spinal fluid will be reported.

The maximum concentration [CMAX] will be calculated based on the CSF pharmacokinetic samples.

Pediatric Brain Tumor Consortium

This is a phase I study and we will use a design similar to the Rolling-6 design and open 6 slots initially on Dose level 1. If we observe no-more than 1 DLT in these 6 subjects then we would expand this cohort to at least 12 patients for PK and additional safety information. If more than 1 DLT is observed on dose level 1 in 2-6 subjects, then further enrollment to dose level 1 will stop, the dose will be de-escalated to dose level 0 and the same approach will be repeated. Based on the above-outlined de-escalation rules, if dose level 0 is found to be too toxic, then the trial will be closed to accrual and the merits of amending or closing the trial permanently will be reconsidered.

Patients will receive one (1) four (4) week cycle of weekly IV PS-341 followed by a standard of care radical prostatectomy 24 to 72 hours later.

PS-341

Age of participants is reported as age at the time of study enrollment.

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

Region of Enrollment

Pour wound healing is defined in the protocol as dehiscence of fascia during the first postoperative week. Excessive bleeding is defined in the protocol as greater than 2 units of blood required during the first 24 hours after surgery.

The Purpose of the Present Study is to Assess the Safety of PS-341 as a Pretreatment in Patients Who Are to Undergo a Radical Prostatectomy. Poor Wound Healing and Excessive Bleeding, With Historical Rates of <1% and 10% Respectively Will be Measured.

Overall Study

Dr. Teresa Hayes - Associate Professor

Prostate Neoplasms

PS-341 is a dipeptidyl boronic acid inhibitor with high specificity for the proteasome developed by Millennium Pharmaceuticals Inc. to treat human malignancies. It is the first member of this class of anti-tumor agents to come to human trials. Patients will receive PS-341 (1.6mg/m2/dose) by intravenous push weekly for 4 consecutive weeks followed by a 24-72 hour rest. This schedule consists of one treatment cycle. Upon the completion of 4 weeks of PS-341 followed by a 24-72 hour rest period, radical prostatectomy will be performed.

PS-341 (bortezomib)

Scott Department of Urology Clinical Trials

anorexia/protease

INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas

PS-341 Followed by Removal of Prostate for Those With Prostate Cancer

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