Ignite Creation Date:
2024-05-06 @ 1:14 PM
Last Modification Date:
2024-10-26 @ 1:11 PM
Study NCT ID:
NCT03979651
Status:
UNKNOWN
Last Update Posted:
2020-05-08
First Post:
2019-06-05
Brief Title:
MEK and Autophagy Inhibition in MetastaticLocally Advanced Unresectable Neuroblastoma RAS NRAS Melanoma
Sponsor:
Hospices Civils de Lyon
Organization:
Hospices Civils de Lyon
Study Overview
Official Title:
MEK and Autophagy Inhibition in MetastaticLocally Advanced Unresectable Neuroblastoma RAS NRAS Melanoma A Phase IbII Trial of Trametinib Plus Hydroxychloroquine in Patients With NRAS Melanoma
Status:
UNKNOWN
Status Verified Date:
2020-05
Last Known Status:
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:
CHLOROTRAMMEL
Brief Summary:
Patients with metastatic Neuroblastoma RAS NRAS melanoma are currently treated with first line immune checkpoint inhibitors nivolumab pembrolizumab Thus far no targeted therapy has been approved in NRAS mutated melanoma as a second line treatment because although the use of a MEK inhibitor binimetinib alone was superior to the gold standard chemotherapy dacarbazine in a phase 3 trial the progression free survival gain was very modest
In vitro and in vivo work from the study teams lab McMAHON Huntsman Cancer Institute HCI Salt Lake City as well as Ravi Amaravardi and Jean Mulchey-Levy suggests that the activation of autophagy is a mechanism of resistance to BRAF and MEK inhibitors in RAS and RAF mutated cancers such as melanoma pediatric brain tumors and pancreatic adenocarcinoma The study team has shown in vivo in four different NRAS mutated melanoma Patient Derived Xenograft PDX models that the combination of the MEK inhibitor trametinib and the autophagy inhibitor chloroquine results in a more dramatic tumor regression and inhibition than trametinib or chloroquine used as single agents Nat Med 2019 Apr254620-627 doi 101038s41591-019-0367-9 Epub 2019 Mar 4 In two of the PDX models the combination resulted in almost complete tumor regression quasi disappearance that was not observed in the single agent treatment arms
Trametinib MEKINISTR is an orally available MEK inhibitor that is currently approved in combination with the BRAF inhibitor dabrafenib TAFINLARR to treat BRAF mutated metastatic melanoma at the standard dosing of 2 milligrams mg once a day Hydroxychloroquine PLAQUENILR is an orally available autophagy inhibitor that has been used for many years to treat autoimmune diseases like lupus sarcoidosis and rheumatoid arthritis at the standard dosing of 400-600mgday For this study the investigating team would like to evaluate the safety and tolerability of the combination of hydroxychloroquine and trametinib in a phase I trial in patients with NRAS mutated metastatic melanoma
In vitro and in vivo work from the study teams lab McMAHON Huntsman Cancer Institute HCI Salt Lake City as well as Ravi Amaravardi and Jean Mulchey-Levy suggests that the activation of autophagy is a mechanism of resistance to BRAF and MEK inhibitors in RAS and RAF mutated cancers such as melanoma pediatric brain tumors and pancreatic adenocarcinoma The study team has shown in vivo in four different NRAS mutated melanoma Patient Derived Xenograft PDX models that the combination of the MEK inhibitor trametinib and the autophagy inhibitor chloroquine results in a more dramatic tumor regression and inhibition than trametinib or chloroquine used as single agents Nat Med 2019 Apr254620-627 doi 101038s41591-019-0367-9 Epub 2019 Mar 4 In two of the PDX models the combination resulted in almost complete tumor regression quasi disappearance that was not observed in the single agent treatment arms
Trametinib MEKINISTR is an orally available MEK inhibitor that is currently approved in combination with the BRAF inhibitor dabrafenib TAFINLARR to treat BRAF mutated metastatic melanoma at the standard dosing of 2 milligrams mg once a day Hydroxychloroquine PLAQUENILR is an orally available autophagy inhibitor that has been used for many years to treat autoimmune diseases like lupus sarcoidosis and rheumatoid arthritis at the standard dosing of 400-600mgday For this study the investigating team would like to evaluate the safety and tolerability of the combination of hydroxychloroquine and trametinib in a phase I trial in patients with NRAS mutated metastatic melanoma
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?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2019-001399-13 | EUDRACT_NUMBER | None | None |