Ignite Creation Date:
2024-05-06 @ 2:01 AM
Last Modification Date:
2024-10-26 @ 11:13 AM
Study NCT ID:
NCT01959633
Status:
COMPLETED
Last Update Posted:
2022-02-24
First Post:
2013-09-27
Brief Title:
Vemurafenib Plus Cobimetinib Plus PEG-interferon in Advanced Melanoma Patients Harboring the V600BRAF Mutation
Sponsor:
Fondazione Melanoma Onlus
Organization:
Fondazione Melanoma Onlus
Study Overview
Official Title:
Phase I-II Study of the Combination Vemurafenib Plus Cobimetinib Plus PEG-interferon in Advanced Melanoma Patients Harboring the V600BRAF Mutation
Status:
COMPLETED
Status Verified Date:
2019-06
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:
VEMUPLINT
Brief Summary:
The hypothesis of this study is to evaluate the safety and the efficacy of VemurafenibPEG-interferon combination and the IFNAR1 upregulation lead by this treatment
Detailed Description:
Phase I A cohort of 3 consecutive patients will be treated at each dose level first step Patients are scheduled to receive at least two courses of therapy cycle every 28 days at the same dose level Escalation of the dose to the next higher level proceeds in absence of dose-limiting toxicity DLT Drug-related toxicities will be evaluated during each cycle of therapy and graded according to the NCI Common Toxicity Criteria
Adverse events AEs and the activity of the treatment in terms of ORR will be assessed as primary endpoints respectively for phase I and phase II other variables will be compared as secondary endpoints
The treatment scheme is Peg-Interferon 123 microgramsKg lyophilized powder 296 and 444 μg vials one time per week Vemurafenib film-coated capsules 960 mg bid Cobimetinib tablets 60 mg od 21 days on followed by 7 days off
Interferon treatment should start after 15 days of Vemurafenib Cobimetinib only
Phase I will be conducted at Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione G Pascale PI Paolo Antonio Ascierto and a minimum of 3 patients per cohort will be enrolled Groups of 3 patients will be entered at each dose level vemurafenib 960 mg bid Cobimetinib 60 mg od 21 days on followed by 7 days off Peg-interferon 123 microgramsKg DLT will be determined after 2 courses of therapy if all 3 patients treated at a dose level have been observed for 2 courses of therapy without DLT then the dose will be escalated If at least 23 patients have DLT after the first 2 courses of therapy in each cohort then the previous dose level will be considered as the MTD If 13 patients have DLT then 3 more patients will be treated at this dose level If none of these patients has DLT then the dose will be escalated If at least one of the 3 additional patients has DLT then the previous dose will be considered the MTD
The maximum tolerated dose MTD is then considered the recommended dose for further evaluation next step
Patients experiencing toxicities that were not dose-limiting can be retreated at the same dose level upon full recovery
Special case is represented by patients with liver metastases for whom ALT or AST increases 3xULN ie Grade 2 of the CTCAE requires a closer monitoring of the liver tests In such cases patients with AT up to 5xULN may be allowed to participate in the trial Therefore a threshold level of ALT or AST 3xBaseline value vs the standard 3xULN threshold is considered to prompt closer monitoring for the whole duration of the treatment Patients with rapidly rising or high serum ALT or AST or with ALT or AST elevations accompanied by jaundice require urgent evaluation to find treatable causes of hepatocellular necrosis
Patients will be treated until progression if the MTD is not reached
Phase II Phase II will be conducted in approximately 10 Investigational sites located in Italy and 42 patients will be enrolled in total including 3 patients from the phase I
Treatment will be continued until progression or unacceptable toxicity
Adverse events AEs and the activity of the treatment in terms of ORR will be assessed as primary endpoints respectively for phase I and phase II other variables will be compared as secondary endpoints
The treatment scheme is Peg-Interferon 123 microgramsKg lyophilized powder 296 and 444 μg vials one time per week Vemurafenib film-coated capsules 960 mg bid Cobimetinib tablets 60 mg od 21 days on followed by 7 days off
Interferon treatment should start after 15 days of Vemurafenib Cobimetinib only
Phase I will be conducted at Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione G Pascale PI Paolo Antonio Ascierto and a minimum of 3 patients per cohort will be enrolled Groups of 3 patients will be entered at each dose level vemurafenib 960 mg bid Cobimetinib 60 mg od 21 days on followed by 7 days off Peg-interferon 123 microgramsKg DLT will be determined after 2 courses of therapy if all 3 patients treated at a dose level have been observed for 2 courses of therapy without DLT then the dose will be escalated If at least 23 patients have DLT after the first 2 courses of therapy in each cohort then the previous dose level will be considered as the MTD If 13 patients have DLT then 3 more patients will be treated at this dose level If none of these patients has DLT then the dose will be escalated If at least one of the 3 additional patients has DLT then the previous dose will be considered the MTD
The maximum tolerated dose MTD is then considered the recommended dose for further evaluation next step
Patients experiencing toxicities that were not dose-limiting can be retreated at the same dose level upon full recovery
Special case is represented by patients with liver metastases for whom ALT or AST increases 3xULN ie Grade 2 of the CTCAE requires a closer monitoring of the liver tests In such cases patients with AT up to 5xULN may be allowed to participate in the trial Therefore a threshold level of ALT or AST 3xBaseline value vs the standard 3xULN threshold is considered to prompt closer monitoring for the whole duration of the treatment Patients with rapidly rising or high serum ALT or AST or with ALT or AST elevations accompanied by jaundice require urgent evaluation to find treatable causes of hepatocellular necrosis
Patients will be treated until progression if the MTD is not reached
Phase II Phase II will be conducted in approximately 10 Investigational sites located in Italy and 42 patients will be enrolled in total including 3 patients from the phase I
Treatment will be continued until progression or unacceptable toxicity
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 |
|---|---|---|---|
| 2013-003730-33 | EUDRACT_NUMBER | None | None |