Ignite Creation Date:
2024-05-06 @ 3:48 PM
Last Modification Date:
2024-10-26 @ 1:57 PM
Study NCT ID:
NCT04760080
Status:
COMPLETED
Last Update Posted:
2021-02-18
First Post:
2021-02-16
Brief Title:
Association of Hydroxychloroquine BRAF and MEK Inhibitors in Metastatic Melanoma a Retrospective Case-control Study
Sponsor:
Hospices Civils de Lyon
Organization:
Hospices Civils de Lyon
Study Overview
Official Title:
Adjunction of Hydroxychloroquine in Patients With a Metastatic Melanoma Who Are Resistant to BRAF and MEK Inhibitors a Retrospective Case-control Study
Status:
COMPLETED
Status Verified Date:
2021-02
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:
CHLORO-DATRAM
Brief Summary:
Patients with a BRAF mutated melanoma are usually treated in France by a first line of immunotherapy followed by a second line that combines a BRAF inhibitor dabrafenib vemurafenib encorafenib and a MEK inhibitor trametinib cobimetinib binimetinib
The combination dabrafenibtrametinib is initially very efficient but it is unfortunately limited because acquired resistances usually occur after a year of treatment Patients who become resistant to dabrafenibtrametinib and immunotherapy unfortunately do not have an approved effective treatment at their disposal They usually receive a palliative chemotherapy by dacarbazine or fotemustine and they have a mean overall survival that is less than three months
Activation of autophagy in presence of BRAF and MEK inhibitors is a known mechanism of resistance to BRAFMEK inhibitors Hydroxychloroquine is an autophagy inhibitor and it has been suggested in vitro that it could decrease resistance to BRAFMEK inhibitors
Following the positive results in 2018 of a phase III study in the USA that showed the efficacy and the absence of toxicity of the association of Dabrafenib Trametinib and hydroxychloroquine when used as a first line treatement we proposed to our patients who had become resistant to the dabrafenibtrametinib combination to pursue their treatment beyond progression and to receive in addition hydroxychloroquine
This prescription was initiated in patients for whom no further therapeutic options were available after validation by a multidisciplinary tumor board All patients were informed that the combination dabrafenibtrametinibhydroxychloroquine was not approved by a regulatory agency
The combination dabrafenibtrametinib is initially very efficient but it is unfortunately limited because acquired resistances usually occur after a year of treatment Patients who become resistant to dabrafenibtrametinib and immunotherapy unfortunately do not have an approved effective treatment at their disposal They usually receive a palliative chemotherapy by dacarbazine or fotemustine and they have a mean overall survival that is less than three months
Activation of autophagy in presence of BRAF and MEK inhibitors is a known mechanism of resistance to BRAFMEK inhibitors Hydroxychloroquine is an autophagy inhibitor and it has been suggested in vitro that it could decrease resistance to BRAFMEK inhibitors
Following the positive results in 2018 of a phase III study in the USA that showed the efficacy and the absence of toxicity of the association of Dabrafenib Trametinib and hydroxychloroquine when used as a first line treatement we proposed to our patients who had become resistant to the dabrafenibtrametinib combination to pursue their treatment beyond progression and to receive in addition hydroxychloroquine
This prescription was initiated in patients for whom no further therapeutic options were available after validation by a multidisciplinary tumor board All patients were informed that the combination dabrafenibtrametinibhydroxychloroquine was not approved by a regulatory agency
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
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