Testing the Ability of AMG 232 (KRT 232) to Get Into the Tumor in Patients With Brain Cancer
Last updated on July 2021Recruitment
- Recruitment Status
- Recruiting
- Estimated Enrollment
- 92
Summary
- Conditions
- Glioblastoma
- Gliosarcoma
- MGMT-Unmethylated Glioblastoma
- Recurrent Glioblastoma
- Type
- Interventional
- Phase
- Phase 1
- Design
- Allocation: N/AIntervention Model: Sequential AssignmentMasking: None (Open Label)Primary Purpose: Treatment
Participation Requirements
- Age
- Between 18 years and 125 years
- Gender
- Both males and females
Description
PRIMARY OBJECTIVES: I. Determine the concentration and variability in concentration of MDM2 inhibitor KRT-232 (AMG 232 [KRT 232]) in brain and brain-associated tissue in patients with recurrent glioblastoma (GBM). (Part 1) II. Determine the maximum tolerated dose (MTD) of AMG 232 (KRT 232) given in ...
PRIMARY OBJECTIVES: I. Determine the concentration and variability in concentration of MDM2 inhibitor KRT-232 (AMG 232 [KRT 232]) in brain and brain-associated tissue in patients with recurrent glioblastoma (GBM). (Part 1) II. Determine the maximum tolerated dose (MTD) of AMG 232 (KRT 232) given in combination with standard radiation following surgery for patients with newly diagnosed GBM harboring unmethylated MGMT promoters and wild-type TP53. (Part 2) SECONDARY OBJECTIVES: I. Determine the safety and toxicity of AMG 232 (KRT 232) in patients with recurrent GBM. (Part 1) II. Assess the variability of AMG 232 (KRT 232) concentration in tumor enhancing versus (vs.) infiltrative tissue. (Part 1) III. Assess the pharmacodynamic effect of AMG 232 (KRT 232) on p21 elevation. (Part 1) IV. Determine the safety of AMG 232 (KRT 232) given concurrently with radiation therapy (RT) and adjuvantly as monotherapy for patients with newly diagnosed GBM harboring unmethylated MGMT promoters and wild-type TP53. (Part 2) V. Assess AMG 232 (KRT 232) exposure and correlations with pharmacodynamic (PD) effect on p21 elevation. (Part 2) VI. Assess PD effect on MIC-1 elevation in serum. (Part 2) OUTLINE: This is a phase 0, intratumoral pharmacokinetic (PK)/PD study of MDM2 inhibitor KRT-232 followed by a phase I dose-escalation study. PART I: Patients with recurrent glioblastoma receive MDM2 inhibitor AMG 232 (KRT-232) orally (PO) once daily (QD) for 2 days. Within 3-6 hours of the last dose, patients undergo standard of care surgery. Upon recovery (within 45 days), patients with TP53 wild-type tumors continue to receive MDM2 inhibitor AMG 232 (KRT-232) PO QD on days 1-7. Cycles repeat every 21 days in absence of disease progression or unacceptable toxicity. PART II: Within 6 weeks of standard of care surgery, patients with newly diagnosed glioblastoma undergo radiation therapy daily during weeks 1-6. Patients also receive MDM2 inhibitor AMG 232 (KRT-232) PO 2 times weekly (days 2, 4), 3 times weekly (days 2, 3, 5), 4 times weekly (days 2, 3, 4, 5), or 5 times weekly (days 1-5) for 6 weeks during radiation therapy. PART II (EXPANSION COHORT): Patients receive MDM2 inhibitor AMG 232 (KRT-232) PO QD on days 1-7. Cycles repeat every 21 days in absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 2 months for the first two years from the off-treatment date, and then every 6 months until death.
Tracking Information
- NCT #
- NCT03107780
- Collaborators
- Not Provided
- Investigators
- Principal Investigator: Eudocia Lee National Cancer Institute (NCI)