Ignite Creation Date:
2024-05-06 @ 1:58 AM
Last Modification Date:
2024-10-26 @ 11:12 AM
Study NCT ID:
NCT01940809
Status:
TERMINATED
Last Update Posted:
2022-03-10
First Post:
2013-09-09
Brief Title:
Ipilimumab With or Without Dabrafenib Trametinib andor Nivolumab in Treating Patients With Melanoma That Is Metastatic or Cannot Be Removed by Surgery
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Sequential Safety and Biomarker Study of BRAF-MEK Inhibition on the Immune Response in the Context of Combined CTLA-4 Blockade and PD-1 Blockade for BRAF Mutant Melanoma
Status:
TERMINATED
Status Verified Date:
2022-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Inadequate accrual rate
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This randomized phase I trial studies the side effects and best way to give ipilimumab with or without dabrafenib trametinib andor nivolumab in treating patients with melanoma that has spread to other parts of the body metastatic or cannot be removed by surgery Monoclonal antibodies such as ipilimumab and nivolumab may interfere with the ability of cancer cells to grow and spread Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth It is not yet known whether ipilimumab works better with or without dabrafenib trametinib andor nivolumab in treating melanoma
Detailed Description:
PRIMARY OBJECTIVES
I To evaluate the safety and tolerability of ipilimumab part 1 or ipilimumab plus nivolumab part 2 following lead-in of v-raf murine sarcoma viral oncogene homolog B1 BRAF and mitogen-activated protein kinase kinase MEK inhibitors either alone or in combination in patients with BRAFV600 mutant melanoma
SECONDARY OBJECTIVES
I To determine the response rate to ipilimumab part 1 or ipilimumab plus nivolumab part 2 after BRAF and MEK inhibitors either alone or in combination compared to no prior kinase inhibitor treatment
II To determine the safety and tolerability of dabrafenib and trametinib combination in the setting of prior ipilimumab alone or ipilimumab preceded by BRAF and MEK inhibitors either alone or in combination part 1
III To determine the safety and tolerability of dabrafenib and trametinib combination in the setting of prior ipilimumab plus nivolumab without prior BRAFMEK inhibition or ipilimumab plus nivolumab preceded by BRAF and MEK inhibitors either alone or in combination part 2
IV To determine the response rate to dabrafenib and trametinib in the setting of prior ipilimumab alone or ipilimumab preceded by BRAF and MEK inhibitors either alone or in combination part 1
V To determine the response rate to dabrafenib and trametinib in the setting of prior ipilimumab plus nivolumab without prior MEKBRAF inhibition or prior ipilimumab plus nivolumab preceded by BRAFMEK inhibitors part 2
VI To obtain peripheral blood and tumor tissue for biomarker analysis VII To describe the immune impact of kinase inhibitor therapy on the immune response associated with ipilimumab treatment part 1 or ipilimumab plus nivolumab treatment part 2
VIII To observe and record anti-tumor activity
OUTLINE Patients are randomized to 1 of 4 treatment arms for Part 2 Part 1 closed to accrual 8252015
PART 1 Closed to accrual as of 8252015 ARM A1 Patients receive dabrafenib orally PO twice daily BID and trametinib PO once daily QD for 25 days Patients then receive ipilimumab intravenously IV over 90 minutes Treatment with ipilimumab repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
ARM B1 Patients receive trametinib PO QD for 25 days Patients then receive ipilimumab IV over 90 minutes Treatment with ipilimumab repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
ARM C1 Patients receive dabrafenib PO BID for 25 days Patients then receive ipilimumab IV over 90 minutes Treatment with ipilimumab repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
ARM D1 Patients receive ipilimumab IV over 90 minutes Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
PART 2
ARM A2 Patients receive dabrafenib PO BID and trametinib PO QD for 25 days followed by nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 4 doses followed by nivolumab monotherapy IV every 2 weeks continuously for up to 42 courses
ARM B2 Patients receive trametinib PO QD for 25 days followed by nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 4 doses followed by nivolumab monotherapy IV every 2 weeks continuously for up to 42 courses
ARM C2 Patients receive dabrafenib PO BID for 25 days followed by nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 4 doses followed by nivolumab monotherapy IV every 2 weeks continuously for up to 42 courses
ARM D2 Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 4 doses followed by nivolumab monotherapy IV every 2 weeks continuously for up to 42 courses
After 12 weeks of treatment with ipilimumab or ipilimumab and nivolumab followed by nivolumab monotherapy all patients may continue to receive dabrafenib PO BID and trametinib PO QD in the absence of disease progression
After completion of study treatment patients are followed up for 14 weeks
I To evaluate the safety and tolerability of ipilimumab part 1 or ipilimumab plus nivolumab part 2 following lead-in of v-raf murine sarcoma viral oncogene homolog B1 BRAF and mitogen-activated protein kinase kinase MEK inhibitors either alone or in combination in patients with BRAFV600 mutant melanoma
SECONDARY OBJECTIVES
I To determine the response rate to ipilimumab part 1 or ipilimumab plus nivolumab part 2 after BRAF and MEK inhibitors either alone or in combination compared to no prior kinase inhibitor treatment
II To determine the safety and tolerability of dabrafenib and trametinib combination in the setting of prior ipilimumab alone or ipilimumab preceded by BRAF and MEK inhibitors either alone or in combination part 1
III To determine the safety and tolerability of dabrafenib and trametinib combination in the setting of prior ipilimumab plus nivolumab without prior BRAFMEK inhibition or ipilimumab plus nivolumab preceded by BRAF and MEK inhibitors either alone or in combination part 2
IV To determine the response rate to dabrafenib and trametinib in the setting of prior ipilimumab alone or ipilimumab preceded by BRAF and MEK inhibitors either alone or in combination part 1
V To determine the response rate to dabrafenib and trametinib in the setting of prior ipilimumab plus nivolumab without prior MEKBRAF inhibition or prior ipilimumab plus nivolumab preceded by BRAFMEK inhibitors part 2
VI To obtain peripheral blood and tumor tissue for biomarker analysis VII To describe the immune impact of kinase inhibitor therapy on the immune response associated with ipilimumab treatment part 1 or ipilimumab plus nivolumab treatment part 2
VIII To observe and record anti-tumor activity
OUTLINE Patients are randomized to 1 of 4 treatment arms for Part 2 Part 1 closed to accrual 8252015
PART 1 Closed to accrual as of 8252015 ARM A1 Patients receive dabrafenib orally PO twice daily BID and trametinib PO once daily QD for 25 days Patients then receive ipilimumab intravenously IV over 90 minutes Treatment with ipilimumab repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
ARM B1 Patients receive trametinib PO QD for 25 days Patients then receive ipilimumab IV over 90 minutes Treatment with ipilimumab repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
ARM C1 Patients receive dabrafenib PO BID for 25 days Patients then receive ipilimumab IV over 90 minutes Treatment with ipilimumab repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
ARM D1 Patients receive ipilimumab IV over 90 minutes Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
PART 2
ARM A2 Patients receive dabrafenib PO BID and trametinib PO QD for 25 days followed by nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 4 doses followed by nivolumab monotherapy IV every 2 weeks continuously for up to 42 courses
ARM B2 Patients receive trametinib PO QD for 25 days followed by nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 4 doses followed by nivolumab monotherapy IV every 2 weeks continuously for up to 42 courses
ARM C2 Patients receive dabrafenib PO BID for 25 days followed by nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 4 doses followed by nivolumab monotherapy IV every 2 weeks continuously for up to 42 courses
ARM D2 Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 4 doses followed by nivolumab monotherapy IV every 2 weeks continuously for up to 42 courses
After 12 weeks of treatment with ipilimumab or ipilimumab and nivolumab followed by nivolumab monotherapy all patients may continue to receive dabrafenib PO BID and trametinib PO QD in the absence of disease progression
After completion of study treatment patients are followed up for 14 weeks
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-2013-01703 | REGISTRY | None | None |
| 13-304 | None | None | None |
| 9377 | OTHER | None | None |
| 9377 | OTHER | None | None |
| P30CA006516 | NIH | None | None |
| U01CA062490 | NIH | None | None |