Ignite Creation Date:
2024-05-06 @ 9:50 AM
Last Modification Date:
2024-10-26 @ 12:20 PM
Study NCT ID:
NCT03088176
Status:
UNKNOWN
Last Update Posted:
2020-10-12
First Post:
2017-03-07
Brief Title:
Combining Talimogene Laherparepvec With BRAF and MEK Inhibitors in BRAF Mutated Advanced Melanoma
Sponsor:
West Cancer Center
Organization:
West Cancer Center
Study Overview
Official Title:
A Phase 1b Trial of Talimogene Laherparepvec in Combination With Dabrafenib and Trametinib in Advanced Melanoma With an Activating BRAF Mutation
Status:
UNKNOWN
Status Verified Date:
2020-10
Last Known Status:
ACTIVE_NOT_RECRUITING
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:
The purpose of the study is to determine safety and tolerability of the combination of talimogene laherparepvec in combination with dabrafenib and trametinib in BRAF mutated advanced melanoma
Detailed Description:
While targeted therapies can successfully block oncogenic signaling in BRAF mutant melanoma activation of an immune response with agents such as talimogene laherparepvec can induce durable responses in a subset of patients Combining BRAF inhibitors and immunotherapy may specifically target the BRAF driver mutation in the tumor cells and potentially sensitize the immune system to target tumors
The study will enroll up to 20 patients with advanced melanoma and activating mutations in the BRAF gene for the local administration of talimogene laherparepvec in conjunction with oral therapy with dabrafenib and trametinib to describe the safety and tolerability of this combination
Talimogene laherparepvec will be administered by intralesional injection into injectable cutaneous subcutaneous or nodal lesions with or without image ultrasound guidance Talimogene laherparepvec will not be administered into any visceral organ or mucosal membrane lesions The initial dose of talimogene laherparepvec is up to 40 mL of 106 plaque forming units PFUmL Subsequent doses of talimogene laherparepvec are up to 40 mL of 108 PFUmL The second dose of talimogene laherparepvec the first dose of the 108 PFU formulation will be administered at least 21 days following the initial dose Subsequent doses will be given approximately every 2 weeks
Dabrafenib at a dose of 150mg will be self-administered orally twice per day Trametinib at a dose 2mg will be self-administered orally once per day
Subjects will be evaluated by physical exam at the beginning of Cycle 1 Week 1 Cycle 2 Week 4 Cycle 3 Week 6 Cycle 4 Week 8 and every two cycles thereafter Subjects will be evaluated for dose-limiting toxicities defined in protocol at Cycle 2 Week 4 Cycle 3 Week 6 and Cycle 4 Week 8 Efficacy evaluation will be performed by tumor measurements using clinical assessment CT or PETCT every 4 cycles with the first non-baseline measurement prior to Cycle 4 Tumor response will be evaluated using RECIST 11 Adverse events will be recorded and graded using the Common Terminology Criteria for Adverse Events Version 40 CTCAE v40 Other safety assessments will include clinical laboratory values and physical exam findings Reporting of adverse events serious adverse events and documentation of concomitant medications will occur as needed and at every cycle Biopsy of a melanoma lesion preferably uninjected should occur at least one day prior to Cycle 4 Week 8 Blood for biomarker analysis will be obtained immediately prior to the on-treatment biopsy or if the on-treatment biopsy cannot be performed immediately prior to Cycle 4 Week 8
The study will enroll up to 20 patients with advanced melanoma and activating mutations in the BRAF gene for the local administration of talimogene laherparepvec in conjunction with oral therapy with dabrafenib and trametinib to describe the safety and tolerability of this combination
Talimogene laherparepvec will be administered by intralesional injection into injectable cutaneous subcutaneous or nodal lesions with or without image ultrasound guidance Talimogene laherparepvec will not be administered into any visceral organ or mucosal membrane lesions The initial dose of talimogene laherparepvec is up to 40 mL of 106 plaque forming units PFUmL Subsequent doses of talimogene laherparepvec are up to 40 mL of 108 PFUmL The second dose of talimogene laherparepvec the first dose of the 108 PFU formulation will be administered at least 21 days following the initial dose Subsequent doses will be given approximately every 2 weeks
Dabrafenib at a dose of 150mg will be self-administered orally twice per day Trametinib at a dose 2mg will be self-administered orally once per day
Subjects will be evaluated by physical exam at the beginning of Cycle 1 Week 1 Cycle 2 Week 4 Cycle 3 Week 6 Cycle 4 Week 8 and every two cycles thereafter Subjects will be evaluated for dose-limiting toxicities defined in protocol at Cycle 2 Week 4 Cycle 3 Week 6 and Cycle 4 Week 8 Efficacy evaluation will be performed by tumor measurements using clinical assessment CT or PETCT every 4 cycles with the first non-baseline measurement prior to Cycle 4 Tumor response will be evaluated using RECIST 11 Adverse events will be recorded and graded using the Common Terminology Criteria for Adverse Events Version 40 CTCAE v40 Other safety assessments will include clinical laboratory values and physical exam findings Reporting of adverse events serious adverse events and documentation of concomitant medications will occur as needed and at every cycle Biopsy of a melanoma lesion preferably uninjected should occur at least one day prior to Cycle 4 Week 8 Blood for biomarker analysis will be obtained immediately prior to the on-treatment biopsy or if the on-treatment biopsy cannot be performed immediately prior to Cycle 4 Week 8
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?:
False
Is an FDA AA801 Violation?:
None