Association of Hydroxychloroquine, BRAF and MEK Inhibitors in Metastatic Melanoma : a Retrospective Case-control Study.

Completed

• Conditions: Dermatology and Oncology
• Interventions: Other: pre-treatment data; Other: during study treatment

• Registration Number: NCT04760080
• Lead Sponsor: Hospices Civils de Lyon

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 dabrafenib/trametinib is initially very efficient but it is unfortunately limited because acquired resistances usually occur after a year of treatment. Patients who become resistant to dabrafenib/trametinib 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 BRAF/MEK inhibitors. Hydroxychloroquine is an autophagy inhibitor and it has been suggested in vitro that it could decrease resistance to BRAF/MEK inhibitors.

Following the positive results in 2018 of a phase I/II 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 dabrafenib/trametinib 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 dabrafenib/trametinib/hydroxychloroquine was not approved by a regulatory agency.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-01-01
• Primary Completion: 2020-10-01
• Study Completion: 2020-10-01
• Status Verified: 2021-02
• Study First Submitted: 2021-02-16
• Study First Submitted QC: 2021-02-16
• Last Update Submitted: 2021-02-16
• Study First Posted: 2021-02-18
• Last Update Posted: 2021-02-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

• Patients with metastatic melanoma with an activating BRAF mutation
• Who received at least one line of immunotherapy
• Whose disease is resistant to a BRAF inhibitor used as a single agent or in combination with a MEK inhibitor
• Who received either cytotoxic chemotherapy or the combination dabrafenib + trametinib + hydroxychloroquine after disease progression to dabrafenib/trametinib from January 2008 to June 2020 in the Dermatology ward of the Lyon Sud Hospital

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Exclusion Criteria

• Patients who did not received an immunotherapy prior to dabrafenib/trametinib treatment
• Absence of tumor board validation

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with a metastatic melanoma treated by dabrafenib/trametinib and hydroxychloroquine.	during study treatment	Patients with a metastatic melanoma treated by dabrafenib/trametinib and hydroxychloroquine after acquired resistance to dabrafenib/trametinib. Patients treated * for a BRAF mutated metastatic melanoma in Pr Dalle's dermatology ward at Centre Hospitalier Lyon Sud, * From January 2008 to June 2020 * who received a treatment by immunotherapy before receiving a treatment by dabrafenib/trametinib * who became resistant to dabrafeib/trametinib * and received after disease progression a treatment by dabrafenib/trametinib and hydroxychloroquine
Patients with a metastatic melanoma treated by dabrafenib/trametinib and hydroxychloroquine.	pre-treatment data	Patients with a metastatic melanoma treated by dabrafenib/trametinib and hydroxychloroquine after acquired resistance to dabrafenib/trametinib. Patients treated * for a BRAF mutated metastatic melanoma in Pr Dalle's dermatology ward at Centre Hospitalier Lyon Sud, * From January 2008 to June 2020 * who received a treatment by immunotherapy before receiving a treatment by dabrafenib/trametinib * who became resistant to dabrafeib/trametinib * and received after disease progression a treatment by dabrafenib/trametinib and hydroxychloroquine

Primary Outcome Measures

Name	Time	Method
Comparison of progression free survival (PFS) in patients who are resistant to dabrafenib/trametinib who receive dabrafenib/trametinib/hydroxychloroquine despite tumor progression versus cytotoxic chemotherapy	Patients treated from January 2008 to June 2020 will be included retrospectively in this study. Data cut off will be defined in June 2020.	Progression Free Survival: the length of time during and after the treatment of a cancer, that a patient lives with the disease but it does not get worse

Trial Locations

Locations (1)

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre-Bénite, France