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

NCT ID: NCT04760080

Last Updated: 2021-02-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 31 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-01-01
• Study Completion Date: 2020-10-01

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.

Conditions

Dermatology and Oncology

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

Patients with a metastatic melanoma treated by dabrafenib/trametinib and hydroxychloroquine.

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

pre-treatment data

Intervention Type: OTHER

We will evaluate in all patients pre-treatment data :

• Melanoma staging at treatment initiation
• Melanoma characteristics at initial diagnosis
• Number and location of metastasis
• Performans status
• Demographic information

during study treatment

Intervention Type: OTHER

We will evaluate in all patients during study treatment :

• Rate of adverse events
• Type of adverse events
• Radiological response to treatment by CTscans that are routinely performed every three months.

Patients with a metastatic melanoma treated by cytotoxic chemotherapy.

Patients with a metastatic melanoma treated by cytotoxic chemotherapy 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 under dabrafenib/trametinib a treatment by cytotoxic chemotherapy

No interventions assigned to this group

Interventions

pre-treatment data

We will evaluate in all patients pre-treatment data :

• Melanoma staging at treatment initiation
• Melanoma characteristics at initial diagnosis
• Number and location of metastasis
• Performans status
• Demographic information

Intervention Type: OTHER

during study treatment

We will evaluate in all patients during study treatment :

• Rate of adverse events
• Type of adverse events
• Radiological response to treatment by CTscans that are routinely performed every three months.

Intervention Type: OTHER

Eligibility Criteria

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

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Victoire REYNAUD, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Lyon Sud, Dermatology unit

Locations

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Countries

France

Other Identifiers

69HCL20_1230

Identifier Type: -

Identifier Source: org_study_id