Dermatology and OncologyCHLORO-DATRAMNCT04760080
Association of Hydroxychloroquine, BRAF and MEK Inhibitors in Metastatic Melanoma : a Retrospective Case-control Study.
An observational study of Dermatology and Oncology, run by Hospices Civils de Lyon at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dermatology and Oncology
- What is being tested?
- pre-treatment data and during study treatment
- How many people
- 31 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jan 2019to 1 Oct 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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 either a treatment by dabrafenib/trametinib and hydroxychloroquine or a cytotoxic chemotherapy
Who may be able to join
- 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
Who cannot join
- Patients who did not received an immunotherapy prior to dabrafenib/trametinib treatment
- Absence of tumor board validation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Adjunction of Hydroxychloroquine in Patients With a Metastatic Melanoma Who Are Resistant to BRAF and MEK Inhibitors : a Retrospective Case-control Study.
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.
Read more
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
- Being tested
- pre-treatment data, during study treatment
- Keywords
- metastatic melanoma, BRAF inhibitor, MEK inhibitor, hydroxychloroquine, autophagy
- Medical subject headings
- Neoplasms, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pre-treatment dataOther
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 treatmentOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: pre-treatment data; Other: during study treatment | |
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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
Measured: Patients treated from January 2008 to June 2020 will be included retrospectively in this study. Data cut off will be defined in June 2020.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2021
- Study start1 Jan 2019
- Primary completion1 Oct 2020
- Study completion1 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dermatology and OncologyStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Victoire REYNAUD, MD, Principal investigator, Centre Hospitalier Lyon Sud, Dermatology unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04760080
- Sponsor's protocol ID
- 69HCL20_1230
- Acronym
- CHLORO-DATRAM
- Status last verified
- Feb 2021
- First submitted
- 16 Feb 2021
- Last updated
- 18 Feb 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunction of Hydroxychloroquine in Patients With a Metastatic Melanoma Who Are Resistant to BRAF and MEK Inhibitors : a Retrospective Case-control Study.
- ClinicalTrials.gov ID
- NCT04760080
- Acronym / sponsor ID
- CHLORO-DATRAM / 69HCL20_1230
- Conditions
- Dermatology and Oncology
- Keywords
- metastatic melanoma, BRAF inhibitor, MEK inhibitor, hydroxychloroquine, autophagy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 1 Oct 2020 (actual)
- Study completion
- 1 Oct 2020 (actual)
- First posted
- 18 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with a metastatic melanoma treated by dabrafenib/trametinib and hydroxychloroquine. | – | Other: pre-treatment data, Other: during study treatmentPatients 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 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 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 either a treatment by dabrafenib/trametinib and hydroxychloroquine or a cytotoxic chemotherapy
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- Patients who did not received an immunotherapy prior to dabrafenib/trametinib treatment
- Absence of tumor board validation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pre-treatment dataWe 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 | Other | Patients with a metastatic melanoma treated by dabrafenib/trametinib and hydroxychloroquine. |
| during study treatmentWe 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. | Other | Patients with a metastatic melanoma treated by dabrafenib/trametinib and hydroxychloroquine. |
Primary outcome
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
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Victoire REYNAUD, MD principal investigator
Centre Hospitalier Lyon Sud, Dermatology unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Dermatology and Oncology, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Patients treated from January 2008 to June 2020 will be included retrospectively in this study. Data cut off will be defined in June 2020.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2021.