Ignite Creation Date:
2024-05-06 @ 9:53 AM
Last Modification Date:
2024-10-26 @ 12:21 PM
Study NCT ID:
NCT03107780
Status:
SUSPENDED
Last Update Posted:
2024-07-01
First Post:
2017-04-10
Brief Title:
Testing the Ability of AMG 232 KRT 232 to Get Into the Tumor in Patients With Brain Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase 0I Study of AMG 232 KRT 232 Concentrations in Brain Tissue in Patients With Recurrent Glioblastoma and of AMG 232 KRT 232 in Combination With Radiation in Patients With Newly Diagnosed Glioblastoma and Unmethylated MGMT Promoters
Status:
SUSPENDED
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Other - Aministrative hold
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial studies the side effects and best dose of navtemadlin in treating patients with glioblastoma brain cancer that is newly diagnosed or has come back recurrent Navtemadlin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
Detailed Description:
PRIMARY OBJECTIVES
I Determine the concentration and variability in concentration of navtemadlin 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 PKPD study of navtemadlin followed by a phase I dose-escalation study
PART I Patients with recurrent glioblastoma receive navtemadlin 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 navtemadlin KRT-232 PO QD on days 1-7 Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients also undergo magnetic resonance imaging MRI at baseline as well as on study andor end of treatment and collection of blood and tissue samples at baseline and on study
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 navtemadlin KRT-232 PO 1 time weekly day 2 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 Patients also undergo MRI at baseline and end of treatment and collection of blood samples at baseline and on study
PART II EXPANSION COHORT Patients receive navtemadlin KRT-232 PO QD on days 1-7 Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients also undergo MRI at baseline on study and end of treatment
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 5 years
I Determine the concentration and variability in concentration of navtemadlin 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 PKPD study of navtemadlin followed by a phase I dose-escalation study
PART I Patients with recurrent glioblastoma receive navtemadlin 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 navtemadlin KRT-232 PO QD on days 1-7 Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients also undergo magnetic resonance imaging MRI at baseline as well as on study andor end of treatment and collection of blood and tissue samples at baseline and on study
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 navtemadlin KRT-232 PO 1 time weekly day 2 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 Patients also undergo MRI at baseline and end of treatment and collection of blood samples at baseline and on study
PART II EXPANSION COHORT Patients receive navtemadlin KRT-232 PO QD on days 1-7 Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients also undergo MRI at baseline on study and end of treatment
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 5 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2017-00568 | REGISTRY | None | None |
| ALLIANCE-ABTC-1604 | None | None | None |
| ABTC-1604 | OTHER | None | None |
| ABTC-1604 | OTHER | None | None |
| U10CA180821 | NIH | None | None |
| UM1CA137443 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA137443 |