Cutaneous MelanomaPhase 2BAP1treatNCT07807878
Trial of Temozolomide in BAP1 Mutated Patients With Advanced or Metastatic Cutaneous Melanoma
A Phase 2 study testing Temozolomide (TMZ) in people with Cutaneous Melanoma, run by Assistance Publique Hopitaux De Marseille.
Trial summary
BAP1, or BRCA1-associated protein 1, is a gene involved in DNA repair via homologous recombination and is considered a tumor suppressor gene. It is lost or inactivated in a large number of tumors, and the presence of germline BAP1 mutations is associated with a syndrome of tumor predisposition. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cutaneous Melanoma
- What is being tested?
- Temozolomide (TMZ)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2027to 1 Jun 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
Who may be able to join
- Adult patient (≥18 years old)
- Patients who have received information about the study and have signed an informed consent form.
- Histopathological confirmation of a diagnosis of stage III (unresectable) or stage IV (metastatic) cutaneous melanoma according to the 8th edition of the AJCC staging system.
- Patient has experienced treatment failure after undergoing at least one line of Immunotherapy with at least one immune checkpoint inhibitor (anti-PD1, anti-PD1+anti-CTLA4, or anti-PD1+anti-LAG3) and one line of targeted therapy combining BRAF and MEK inhibitors, if indicated.
- The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or lower.
- The patient must have at least one measurable lesion defined by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).
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- The patient must have a pathogenic BAP1 alteration identified by a molecular biology technique in tumor tissue or in circulating cell-free DNA.
- The inclusion of patients is subject to the following criteria:
- Absolute neutrophil count ≥ 1.5 x 109/L (≥ 1500 per mm3)
- Platelet count ≥ 100 x 109/L
- Hemoglobin ≥ 9 g/dL
- ASAT and/or ALAT ≤ 2.5 x Upper Limit of Normal (ULN); patient with liver metastases ≤ 5 × ULN
- Total bilirubin ≤ 1.5 x ULN
- Creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min for patients with creatinine levels > 1.5 x ULN (according to Cockroft-Gault Appendix D) ;
- International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
- Female patients with a negative highly sensitive pregnancy test, or postmenopausal female patients.
Who cannot join
- Patients with non-cutaneous melanoma, whether uveal, mucosal, of unknown primary origin or leptomeningeal
- Patients who have received a minimum of one line of chemotherapy for melanoma treatment
- Positive serology results for human immunodeficiency virus (HIV), active hepatitis B or C infection (acute or chronic) or uncontrolled infection
- Concomitant presence or history of another malignancy, except for the following: appropriately treated squamous or basal cell carcinoma of the skin (adequate healing is required prior to study entry); any other solid tumor, curatively treated and without evidence of recurrence for at least 2 years prior to study entry.
- Participation in or ongoing treatment with another investigational agent or use of an investigational device within 28 days prior to study treatment.
- NB: Participants who have entered the follow-up phase if an investigational study may participate as long as it has been 4 weeks or an interval of five-half-lives, whichever the shortest is, after the last dose of the previous investigational agent.
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- Subjects covered by Articles L1121-5 through L1121-8 of the Public Health Code (minors, adults under guardianship or conservatorship, patients deprived of their liberty, and pregnant or breastfeeding women).
- Any pathology that, in the investigator's opinion, may be a contraindication to the patient's participation in the clinical study, for reasons of safety or compliance with clinical study procedures.
- Patient with hypersensitivity to IMP temozolomide (including hypersensitivity to dacarbazine, severe myelosuppression) or to any of its excipients.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Phase II Trial of Temozolomide in BAP1 Mutated Patients With Advanced or Metastatic Cutaneous Melanoma
BAP1, or BRCA1-associated protein 1, is a gene involved in DNA repair via homologous recombination and is considered a tumor suppressor gene. It is lost or inactivated in a large number of tumors, and the presence of germline BAP1 mutations is associated with a syndrome of tumor predisposition.
Following our team's observation of two exceptional responses to temozolomide in patients who had reached a therapeutic impasse-one of which lasted 11 months and involved both intracerebral and extracerebral tumors-we hypothesize that this mutation may lead to increased susceptibility to chemotherapy.
Read the detailed description
Although the therapeutic management of melanoma has undergone a revolution over the past decade with the advent of immune checkpoint inhibitors on the one hand, and BRAF- and MEK-targeted therapies in patients harboring a BRAF V600 mutation on the other hand, half of patients do not achieve a durable response to these strategies. In light of these major advances, chemotherapy has gradually been abandoned, even in patients with limited therapeutic options, because of its very low response rate.
BAP1, or BRCA1-associated protein 1, is involved in DNA repair through homologous recombination and is considered a tumor suppressor gene. It is lost or inactivated in a wide range of tumors, and the presence of germline BAP1 mutations is associated with a tumor predisposition syndrome (BAP1 tumor predisposition syndrome, BAP1-TPDS).
Following the observation by our team of two exceptional responses, both intracranial and extracranial, lasting more than six months, in two young patients with metastatic melanoma harboring a constitutional BAP1 mutation, treated in the third and eighth lines of therapy, respectively, we hypothesize that this mutation may confer increased susceptibility to chemotherapy, as has been reported in pleural mesothelioma. This increased susceptibility could help guide the therapeutic strategy for affected patients, who account for approximately 1% of cutaneous melanomas in the germline setting and 5-17% of cutaneous melanomas when somatic mutations are considered.
As it remains unclear whether this effect is restricted to germline BAP1 mutations, we chose to include both germline and somatic BAP1 mutations in this study. This is particularly relevant because, in routine clinical practice, the germline or somatic nature of a BAP1 mutation is often determined at a later stage. Somatic mutation testing is frequently performed only as part of a molecular biology panel before predictive medicine strategies are considered, guided by molecular tumor boards, in patients with limited therapeutic options.
Validation of this hypothesis could make it possible to identify patients who may benefit from this readily available and inexpensive treatment.
- Conditions
- Cutaneous Melanoma
- Being tested
- Temozolomide (TMZ)
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Temozolomide (TMZ)Drug
Patients will be treated at a dose of 200mg/m2 from day 1 to day 5, every 28 days, for up to two years
| Study group | Role | What they receive |
|---|---|---|
| patients with advanced cutaneous melanoma with a BAP1 mutation | Experimental | Patient will be treated with temozolomide at a dose of 200mg/m2 from day 1 to day 5, every 28 days, for up to two years Receives: Drug: Temozolomide (TMZ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate at day 84
Overall response rate will be defined as the percentage of patients with a partial response or a complete response according to RECIST 1.1 criteria.
Measured: 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2026
- Study start1 Jun 2027 (estimated)
- Primary completion1 Jan 2030 (estimated)
- Study completion1 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cutaneous MelanomaStudies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nausicaa MALISSEN, Doctor, Principal investigator, assistance publique - hôpitaux de Marseille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07807878
- Sponsor's protocol ID
- RCAPHM25_0408_BAPtreat
- Other IDs
- 2026-527858-40-00
- Acronym
- BAP1treat
- Status last verified
- Sep 2026
- First submitted
- 2 Sep 2026
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Temozolomide in BAP1 Mutated Patients With Advanced or Metastatic Cutaneous Melanoma
- ClinicalTrials.gov ID
- NCT07807878
- Acronym / sponsor ID
- BAP1treat / RCAPHM25_0408_BAPtreat
- Conditions
- Cutaneous Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- 1 Jun 2027 (estimated)
- Primary completion
- 1 Jan 2030 (estimated)
- Study completion
- 1 Jun 2031 (estimated)
- First posted
- 8 Sep 2026 (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.
BAP1, or BRCA1-associated protein 1, is a gene involved in DNA repair via homologous recombination and is considered a tumor suppressor gene. It is lost or inactivated in a large number of tumors, and the presence of germline BAP1 mutations is associated with a syndrome of tumor predisposition.
Following our team's observation of two exceptional responses to temozolomide in patients who had reached a therapeutic impasse-one of which lasted 11 months and involved both intracerebral and extracerebral tumors-we hypothesize that this mutation may lead to increased susceptibility to chemotherapy.
Detailed description
Although the therapeutic management of melanoma has undergone a revolution over the past decade with the advent of immune checkpoint inhibitors on the one hand, and BRAF- and MEK-targeted therapies in patients harboring a BRAF V600 mutation on the other hand, half of patients do not achieve a durable response to these strategies. In light of these major advances, chemotherapy has gradually been abandoned, even in patients with limited therapeutic options, because of its very low response rate.
BAP1, or BRCA1-associated protein 1, is involved in DNA repair through homologous recombination and is considered a tumor suppressor gene. It is lost or inactivated in a wide range of tumors, and the presence of germline BAP1 mutations is associated with a tumor predisposition syndrome (BAP1 tumor predisposition syndrome, BAP1-TPDS).
Following the observation by our team of two exceptional responses, both intracranial and extracranial, lasting more than six months, in two young patients with metastatic melanoma harboring a constitutional BAP1 mutation, treated in the third and eighth lines of therapy, respectively, we hypothesize that this mutation may confer increased susceptibility to chemotherapy, as has been reported in pleural mesothelioma. This increased susceptibility could help guide the therapeutic strategy for affected patients, who account for approximately 1% of cutaneous melanomas in the germline setting and 5-17% of cutaneous melanomas when somatic mutations are considered.
As it remains unclear whether this effect is restricted to germline BAP1 mutations, we chose to include both germline and somatic BAP1 mutations in this study. This is particularly relevant because, in routine clinical practice, the germline or somatic nature of a BAP1 mutation is often determined at a later stage. Somatic mutation testing is frequently performed only as part of a molecular biology panel before predictive medicine strategies are considered, guided by molecular tumor boards, in patients with limited therapeutic options.
Validation of this hypothesis could make it possible to identify patients who may benefit from this readily available and inexpensive treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| patients with advanced cutaneous melanoma with a BAP1 mutation | Experimental | Drug: Temozolomide (TMZ)Patient will be treated with temozolomide at a dose of 200mg/m2 from day 1 to day 5, every 28 days, for up to two years |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Adult patient (≥18 years old)
- Patients who have received information about the study and have signed an informed consent form.
- Histopathological confirmation of a diagnosis of stage III (unresectable) or stage IV (metastatic) cutaneous melanoma according to the 8th edition of the AJCC staging system.
- Patient has experienced treatment failure after undergoing at least one line of Immunotherapy with at least one immune checkpoint inhibitor (anti-PD1, anti-PD1+anti-CTLA4, or anti-PD1+anti-LAG3) and one line of targeted therapy combining BRAF and MEK inhibitors, if indicated.
- The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or lower.
Key exclusion criteria (9 listed)
- Patients with non-cutaneous melanoma, whether uveal, mucosal, of unknown primary origin or leptomeningeal
- Patients who have received a minimum of one line of chemotherapy for melanoma treatment
- Positive serology results for human immunodeficiency virus (HIV), active hepatitis B or C infection (acute or chronic) or uncontrolled infection
- Concomitant presence or history of another malignancy, except for the following: appropriately treated squamous or basal cell carcinoma of the skin (adequate healing is required prior to study entry); any other solid tumor, curatively treated and without evidence of recurrence for at least 2 years prior to study entry.
- Participation in or ongoing treatment with another investigational agent or use of an investigational device within 28 days prior to study treatment.
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 |
|---|---|---|
| Temozolomide (TMZ)Patients will be treated at a dose of 200mg/m2 from day 1 to day 5, every 28 days, for up to two years | Drug | patients with advanced cutaneous melanoma with a BAP1 mutation |
Primary outcome
Overall response rate at day 84
Time frame: 84 days
Overall response rate will be defined as the percentage of patients with a partial response or a complete response according to RECIST 1.1 criteria.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2026.
- Individual participant dataSharing planned: No
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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.
Nausicaa MALISSEN, Doctor principal investigator
assistance publique - hôpitaux de Marseille
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Temozolomide (TMZ) in people with Cutaneous Melanoma, run by Assistance Publique Hopitaux De Marseille.
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 16 inclusion and 9 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: opening soon, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clement PIERRE, PhD (+33491435796, clement.pierre@ap-hm.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate at day 84 (time frame: 84 days). 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 8 Sep 2026; AzTrials last refreshed its copy on 7 Nov 2026.