Ignite Creation Date:
2024-05-06 @ 2:40 AM
Last Modification Date:
2024-10-26 @ 11:21 AM
Study NCT ID:
NCT02097225
Status:
TERMINATED
Last Update Posted:
2022-06-30
First Post:
2014-03-24
Brief Title:
Onalespib Dabrafenib and Trametinib in Treating Patients With BRAF-Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase I Study of AT13387 in Combination With Dabrafenib and Trametinib in Patients With BRAF-Mutant Melanoma and Other Solid Tumors
Status:
TERMINATED
Status Verified Date:
2024-09
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Drug supply issues
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 onalespib when given together with dabrafenib and trametinib in treating patients with BRAF-mutant melanoma or solid tumors that have spread to another place in the body metastatic or cannot be removed by surgery Onalespib dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
Detailed Description:
PRIMARY OBJECTIVES
I To determine the maximum tolerated dose MTD toxicity and safety profile of onalespib AT13387 given weekly in combination with dabrafenib and trametinib in patients with BRAF-mutant metastatic or unresectable solid tumors
SECONDARY OBJECTIVES
I To obtain preliminary estimates of the objective response rate ORR and progression-free survival PFS and document the 6-month PFS and 1-year overall survival OS of patients with BRAF-mutant metastatic or unresectable melanoma treated with AT13387 given weekly in combination with dabrafenib and trametinib
II To describe the pharmacokinetics of treatment with dabrafenib trametinib and AT13387
OUTLINE This is a dose-escalation study of onalespib Four dose levels plus a fallback dose are specified in the protocol and are summarized below The trial is based on a standard 33 design with dose escalation beginning in dose level 1 DL1 In a 33 design three patients are initially enrolled into a given dose cohort If there is no dose limiting toxicity DLT observed in any of these subjects the trial proceeds to enroll additional subjects into the next higher dose cohort If one subject develops a DLT at a specific dose an additional three subjects are enrolled into that same dose cohort Development of DLTs in more than 1 of 6 subjects in a specific dose cohort suggests that the maximum total dose MTD has been exceeded and further dose escalation is not pursued Fallback dose level -1 is initiated if more than 1 of 6 subjects in dose level 1 starting dose develop DLTs
Patients receive dabrafenib orally PO twice daily BID trametinib PO once daily QD on days 1-28 and onalespib intravenously IV over 1 hour on days 1 8 and 15 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Dose Level -1 fallback dose
Dabrafenib 75 mg
Trametinib 1 mg
Onalespib 180 mgm2
Dose Level 1 starting dose
Dabrafenib 150 mg
Trametinib 1 mg
Onalespib 180 mgm2
Dose Level 2
Dabrafenib 150 mg
Trametinib 2 mg
Onalespib 180 mgm2
Dose Level 3
Dabrafenib 150 mg
Trametinib 2 mg
Onalespib 220 mgm2
Dose Level 4
Dabrafenib 150 mg
Trametinib 2 mg
Onalespib 260 mgm2
After completion of study treatment patients are followed up at 28 days and every 6 months for up to 2 years
I To determine the maximum tolerated dose MTD toxicity and safety profile of onalespib AT13387 given weekly in combination with dabrafenib and trametinib in patients with BRAF-mutant metastatic or unresectable solid tumors
SECONDARY OBJECTIVES
I To obtain preliminary estimates of the objective response rate ORR and progression-free survival PFS and document the 6-month PFS and 1-year overall survival OS of patients with BRAF-mutant metastatic or unresectable melanoma treated with AT13387 given weekly in combination with dabrafenib and trametinib
II To describe the pharmacokinetics of treatment with dabrafenib trametinib and AT13387
OUTLINE This is a dose-escalation study of onalespib Four dose levels plus a fallback dose are specified in the protocol and are summarized below The trial is based on a standard 33 design with dose escalation beginning in dose level 1 DL1 In a 33 design three patients are initially enrolled into a given dose cohort If there is no dose limiting toxicity DLT observed in any of these subjects the trial proceeds to enroll additional subjects into the next higher dose cohort If one subject develops a DLT at a specific dose an additional three subjects are enrolled into that same dose cohort Development of DLTs in more than 1 of 6 subjects in a specific dose cohort suggests that the maximum total dose MTD has been exceeded and further dose escalation is not pursued Fallback dose level -1 is initiated if more than 1 of 6 subjects in dose level 1 starting dose develop DLTs
Patients receive dabrafenib orally PO twice daily BID trametinib PO once daily QD on days 1-28 and onalespib intravenously IV over 1 hour on days 1 8 and 15 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Dose Level -1 fallback dose
Dabrafenib 75 mg
Trametinib 1 mg
Onalespib 180 mgm2
Dose Level 1 starting dose
Dabrafenib 150 mg
Trametinib 1 mg
Onalespib 180 mgm2
Dose Level 2
Dabrafenib 150 mg
Trametinib 2 mg
Onalespib 180 mgm2
Dose Level 3
Dabrafenib 150 mg
Trametinib 2 mg
Onalespib 220 mgm2
Dose Level 4
Dabrafenib 150 mg
Trametinib 2 mg
Onalespib 260 mgm2
After completion of study treatment patients are followed up at 28 days and every 6 months for up to 2 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| UM1CA186709 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA186709 |
| NCI-2014-00615 | REGISTRY | None | None |
| CTEP9557 | None | None | None |
| 14-186 | None | None | None |
| 9557 | OTHER | None | None |
| 9557 | OTHER | None | None |
| P30CA006516 | NIH | None | None |
| U01CA062490 | NIH | None | None |