Nicholas Butowski
Nicholas Butowski
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.
Glioblastoma
Recurrent Glioblastoma
RMC-5552
Phase 1
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.}}
Study Type : | Interventional |
Estimated Enrollment : | 48 participants |
Masking : | None (Open Label) |
Primary Purpose : | Treatment |
Official Title : | A Phase I/Ib, Open-Label, Dose-Escalation Study of RMC-5552 Monotherapy in Adult Subjects With Recurrent Glioblastoma |
Actual Study Start Date : | April 3, 2023 |
Estimated Primary Completion Date : | December 31, 2025 |
Estimated Study Completion Date : | December 31, 2025 |
Arm | Intervention/treatment |
---|---|
Experimental: Cohort A 1(Dose Escalation, Recurrent Non-surgical GBM) Participants will start at dose level 1 (6 mg) of RMC-5552 administered intravenously. Participants will receive RMC-5552 weekly in 21-day cycles until disease progression or unacceptable toxicity. |
Drug: RMC-5552 |
Experimental: Cohort A2 (Dose Escalation, Recurrent Non-surgical GBM) Participants receive dose level 2 (12 mg) of RMC-5552 administered intravenously if the toxicity profile from participants in dose level 1 (A1) is acceptable. Participants will receive RMC-5552 weekly in 21-day cycles until disease progression or unacceptable toxicity. |
Drug: RMC-5552 |
Experimental: Cohort B (Dose Expansion, Recurrent Surgical GBM) Participants will receive a single dose of RMC-5552 at the RP2D approximately 4 hours prior to participants' scheduled surgical resection as part of standard of care. After recovering from surgery (about 3-6 weeks), participants will continue receiving RMC-5552 weekly in 21-day cycles until disease progression or unacceptable toxicity. |
Drug: RMC-5552 |
Experimental: Cohort C (Dose Expansion, Recurrent Non-surgical GBM) Participants will be given the RP2D of RMC-5552 weekly in 21-day cycles until disease progression or unacceptable toxicity |
Drug: RMC-5552 |
Ages Eligible for Study: | 18 Years |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.
Recruiting
University of California, San Francisco
San Francisco, California, United States, 94143