Ignite Creation Date:
2024-05-06 @ 3:03 AM
Last Modification Date:
2024-10-26 @ 11:27 AM
Study NCT ID:
NCT02196181
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-07-11
First Post:
2014-07-18
Brief Title:
Dabrafenib and Trametinib for the Treatment of Patients With Stage III-IV BRAF Mutant Melanoma That Cannot Be Removed by Surgery
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Randomized Phase II Trial of Intermittent Versus Continuous Dosing of Dabrafenib NSC-763760 and Trametinib NSC-763093 in BRAF V600EK Mutant Melanoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial studies how well dabrafenib and trametinib work in treating patients with stage III-IV melanoma that cannot be removed by surgery and contains a B-Raf proto-oncogene serinethreonine kinase BRAF mutation Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
Detailed Description:
PRIMARY OBJECTIVE
I To compare progression-free survival with intermittent dosing and continuous dosing of dabrafenib and trametinib among patients with metastatic BRAF V600EK mutant melanoma
SECONDARY OBJECTIVES
I To estimate the frequency and severity of toxicities of the two dosing schedules
II To compare the frequency and severity of fever grade 1 per Common Terminology Criteria for Adverse Events CTCAE 40 of the two dosing schedules
III To compare the response rate complete and partial response confirmed and unconfirmed overall survival and survival after progression between the two dosing schedules on step 2
TRANSLATIONAL MEDICINE OBJECTIVES
I To evaluate whether acquired molecular events leading to reactivation of the MAPK pathway are more common among patients on the continuous dosing arm than on the intermittent dosing arm using circulating tumor deoxyribonucleic acid DNA ctDNA
II To assess the prognostic association between baseline biomarkers and early molecular events with progression free survival PFS
III To explore the potential interaction between treatment arm and baseline biomarkersearly molecular events with PFS
IV To bank tissue and whole blood in anticipation of future studies to evaluate molecular events associated with clinical benefit and disease progression in patients treated with continuous versus intermittent dabrafenib and trametinib
OUTLINE Patients are randomized to 1 of 2 treatment arms
ARM I CONTINUOUS DOSING Patients receive dabrafenib orally PO twice daily BID and trametinib PO once daily QD on days 1-56 of each cycle Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity Patients also undergo positron emission tomographycomputed tomography PETCT or CT scans in week 1 of cycle 2 and at off treatment follow up prior to progression Additionally patients undergo blood sample collection echocardiography ECHO or multigated acquisition scan MUGA on study
ARM II INTERMITTENT DOSING Patients receive dabrafenib PO BID and trametinib PO QD on days 1-7 and 29-56 of each cycle Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity Patients also undergo PETCT or CT scans in week 1 of cycle 2 and at off treatment follow up prior to progression Additionally patients undergo blood sample collection ECHO or MUGA on study
After completion of study treatment patients are followed up every 6 months for 3 years and then yearly for 2 years
I To compare progression-free survival with intermittent dosing and continuous dosing of dabrafenib and trametinib among patients with metastatic BRAF V600EK mutant melanoma
SECONDARY OBJECTIVES
I To estimate the frequency and severity of toxicities of the two dosing schedules
II To compare the frequency and severity of fever grade 1 per Common Terminology Criteria for Adverse Events CTCAE 40 of the two dosing schedules
III To compare the response rate complete and partial response confirmed and unconfirmed overall survival and survival after progression between the two dosing schedules on step 2
TRANSLATIONAL MEDICINE OBJECTIVES
I To evaluate whether acquired molecular events leading to reactivation of the MAPK pathway are more common among patients on the continuous dosing arm than on the intermittent dosing arm using circulating tumor deoxyribonucleic acid DNA ctDNA
II To assess the prognostic association between baseline biomarkers and early molecular events with progression free survival PFS
III To explore the potential interaction between treatment arm and baseline biomarkersearly molecular events with PFS
IV To bank tissue and whole blood in anticipation of future studies to evaluate molecular events associated with clinical benefit and disease progression in patients treated with continuous versus intermittent dabrafenib and trametinib
OUTLINE Patients are randomized to 1 of 2 treatment arms
ARM I CONTINUOUS DOSING Patients receive dabrafenib orally PO twice daily BID and trametinib PO once daily QD on days 1-56 of each cycle Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity Patients also undergo positron emission tomographycomputed tomography PETCT or CT scans in week 1 of cycle 2 and at off treatment follow up prior to progression Additionally patients undergo blood sample collection echocardiography ECHO or multigated acquisition scan MUGA on study
ARM II INTERMITTENT DOSING Patients receive dabrafenib PO BID and trametinib PO QD on days 1-7 and 29-56 of each cycle Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity Patients also undergo PETCT or CT scans in week 1 of cycle 2 and at off treatment follow up prior to progression Additionally patients undergo blood sample collection ECHO or MUGA on study
After completion of study treatment patients are followed up every 6 months for 3 years and then yearly for 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 |
|---|---|---|---|
| NCI-2014-01470 | REGISTRY | None | None |
| S1320 | OTHER | None | None |
| S1320 | OTHER | None | None |
| U10CA032102 | NIH | None | None |
| U10CA180888 | NIH | CTEP | httpsreporternihgovquickSearchU10CA180888 |