Ignite Creation Date:
2024-05-06 @ 10:42 AM
Last Modification Date:
2024-10-26 @ 12:34 PM
Study NCT ID:
NCT03332589
Status:
TERMINATED
Last Update Posted:
2022-05-20
First Post:
2017-10-30
Brief Title:
E6201 Plus Dabrafenib for the Treatment of Metastatic Melanoma Central Nervous System Metastases CNS
Sponsor:
Spirita Oncology LLC
Organization:
Spirita Oncology LLC
Study Overview
Official Title:
A Phase 1 Study of E6201 Plus Dabrafenib for the Treatment of Central Nervous System Metastases CNS From BRAF V600-Mutated Metastatic Melanoma
Status:
TERMINATED
Status Verified Date:
2021-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Single center study Principal Investigator left institution
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a Phase 1 study of E6201 plus dabrafenib for the treatment of CNS metastases in BRAF V600-mutated metastatic melanoma A total of up to N28-34 subjects with melanoma metastasized to the CNS will be included
Detailed Description:
Selected subjects will be both males and females age 18 years histologically confirmed melanoma with BRAF V600 mutation with CNS metastasis archived tumor sample from the primary recurrent or metastatic disease with documented BRAF mutation recovered from all acute toxicities Grade 1 due to prior immunotherapy determined to have adequate renal and hepatic function and no known history of significant cardiac disease
Monotherapy Safety Run-in Phase Following screening a total of up to 4 subjects were enrolled E6201 was administered by intravenous IV infusion over a 2-hour period at a dose of 320 mgm2 twice weekly Days 1 4 8 11 15 and 18 for three weeks repeated every 28 days 1 cycle until progression of disease observation of unacceptable adverse events intercurrent illness or changes in the subjects condition that prevents further study participation
Combination Safety Run-in Phase Following screening a total of 6-12 subjects are anticipated to establish the recommended doses of E6201 plus dabrafenib E6201 will be administered by IV infusion over a 2-hour period twice weekly Days 1 4 8 11 15 and 18 repeated every 28 days plus dabrafenib orally twice daily 1 cycle
Dose Level 1 E6201 320 mgm2 twice weekly plus dabrafenib 150 mg BID Dose Level -1 E6201 240 mgm2 twice weekly plus dabrafenib 150 mg BID Dose Level -2 E6201 240 mgm2 twice weekly plus dabrafenib 100 mg BID Dose Level -3 E6201 160 mgm2 twice weekly plus dabrafenib 100 mg BID Dose Level -4 E6201 160 mgm2 twice weekly plus dabrafenib 75 mg BID Dose Level -5 E6201 160 mgm2 twice weekly plus dabrafenib 50 mg BID
A total of 6 subjects will be treated at the combined MTD doses for both drugs in the Combination Safety Run-in Phase before beginning the Expansion Phase
Expansion Phase An additional cohort of up to N18 subjects will be treated at the E6201 plus dabrafenib combined MTD Subjects treated at the MTD in the Combination Safety Run-in Phase will count towards accrual in the Expansion Phase
CNS disease response will be assessed according to 2 methodologies Response Evaluation Criteria in Solid Tumors RECIST v 11 and Response Assessment in Neuro-Oncology - Brain Metastases RANO-BM Non-CNS systemic disease will be assessed according to RECIST v 11
Blood for hematology and serum chemistry determinations will be collected and ECGs will be taken during the study Assessments will be obtained at Week 8 and every 8 weeks thereafter until documented progression of disease PD Subjects who demonstrate clinical benefit will be allowed to continue therapy with E6201 until progression of disease observation of unacceptable adverse events intercurrent illness or changes in the subjects condition that prevents further study participation
Monotherapy Safety Run-in Phase Following screening a total of up to 4 subjects were enrolled E6201 was administered by intravenous IV infusion over a 2-hour period at a dose of 320 mgm2 twice weekly Days 1 4 8 11 15 and 18 for three weeks repeated every 28 days 1 cycle until progression of disease observation of unacceptable adverse events intercurrent illness or changes in the subjects condition that prevents further study participation
Combination Safety Run-in Phase Following screening a total of 6-12 subjects are anticipated to establish the recommended doses of E6201 plus dabrafenib E6201 will be administered by IV infusion over a 2-hour period twice weekly Days 1 4 8 11 15 and 18 repeated every 28 days plus dabrafenib orally twice daily 1 cycle
Dose Level 1 E6201 320 mgm2 twice weekly plus dabrafenib 150 mg BID Dose Level -1 E6201 240 mgm2 twice weekly plus dabrafenib 150 mg BID Dose Level -2 E6201 240 mgm2 twice weekly plus dabrafenib 100 mg BID Dose Level -3 E6201 160 mgm2 twice weekly plus dabrafenib 100 mg BID Dose Level -4 E6201 160 mgm2 twice weekly plus dabrafenib 75 mg BID Dose Level -5 E6201 160 mgm2 twice weekly plus dabrafenib 50 mg BID
A total of 6 subjects will be treated at the combined MTD doses for both drugs in the Combination Safety Run-in Phase before beginning the Expansion Phase
Expansion Phase An additional cohort of up to N18 subjects will be treated at the E6201 plus dabrafenib combined MTD Subjects treated at the MTD in the Combination Safety Run-in Phase will count towards accrual in the Expansion Phase
CNS disease response will be assessed according to 2 methodologies Response Evaluation Criteria in Solid Tumors RECIST v 11 and Response Assessment in Neuro-Oncology - Brain Metastases RANO-BM Non-CNS systemic disease will be assessed according to RECIST v 11
Blood for hematology and serum chemistry determinations will be collected and ECGs will be taken during the study Assessments will be obtained at Week 8 and every 8 weeks thereafter until documented progression of disease PD Subjects who demonstrate clinical benefit will be allowed to continue therapy with E6201 until progression of disease observation of unacceptable adverse events intercurrent illness or changes in the subjects condition that prevents further study participation
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