PRIMARY OBJECTIVES:~I. To determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) of mTORC1 kinase inhibitor RMC-5552 (RMC- 5552). (Cohort A).~II. To characterize the safety and tolerability of RMC-5552 monotherapy. (Cohort A).~III. To characterize the pharmacokinetics (PK) of RMC-5552 after a single dose of RMC-5552 prior to surgical resection. (Cohort B).~IV. To evaluate the preliminary antitumor effect of RMC-5552. (Cohort C).~SECONDARY OBJECTIVES:~I. To measure the pharmacokinetics (PK) of RMC-5552. (Cohort A). II. To evaluate the preliminary antitumor effect of RMC-5552. (Cohort A). III. To assess pharmacodynamic (PD) markers of drug activity, including biochemical markers of mTORC1 pathway inhibition in tumor tissue. (Cohort B).~IV. To characterize the safety and tolerability of RMC-5552 monotherapy. (Cohort B).~V. To evaluate the preliminary antitumor effect of RMC-5552 in recurrent glioblastoma multiforme (GBM). (Cohort B).~VI. To characterize the safety and tolerability of RMC-5552 monotherapy. (Cohort C).~VII. To measure the PK of RMC-5552. (Cohort C).~OUTLINE: This is a phase I, dose-escalation study (Cohort A) followed by a phase Ib study (Cohorts B and C). Patients are assigned to 1 of 3 cohorts.~COHORT A: Non-surgical patients receive RMC-5552 intravenously (IV) on study. Patients undergo a pulmonary function test and chest x-ray during screening. Patients also undergo a brain magnetic resonance imaging (MRI) throughout the trial. Patents undergo blood sample collection on study.~COHORT B: Surgical patients receive a single dose of RP2D RMC-5552 IV prior to standard of care surgery and then on study. Patients undergo a pulmonary function test and chest x-ray during screening. Patients also undergo a brain MRI throughout the trial. Patents undergo blood sample collection on study.~COHORT C: Non-surgical patients receive RP2D of RMC-5552 IV on study. Patients undergo a pulmonary function test and chest x-ray during screening. Patients also undergo a brain MRI throughout the trial. Patents undergo blood sample collection on study.
This phase I/Ib trial tests the side effects, best dose, tolerability, and effectiveness of RMC-5552 in treating patients with glioblastoma that has come back (recurrent). RMC-5552 is a type of medicine called an mechanistic target of rapamycin (mTOR) inhibitor. These types of drugs prevent the formation of a specific group of proteins called mTOR. This protein controls cancer cell growth, and the study doctors believe stopping mTOR from forming may help to kill tumor cells.