Trial of Temozolomide in BAP1 Mutated Patients With Advanced or Metastatic Cutaneous Melanoma

NCT07807878 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: RCAPHM25_0408_BAPtreat2026-527858-40-00
• Study Type: interventional
• Target: 28
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Cutaneous Melanoma

Outcome Measures

Primary Outcomes (1)

• 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.

  84 days

Study Arms (1)

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

Drug: Temozolomide (TMZ)

Interventions

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

patients with advanced cutaneous melanoma with a BAP1 mutation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• The patient must have a pathogenic BAP1 alteration identified by a molecular biology technique in tumor tissue or in circulating cell-free DNA.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

MeSH Terms

Conditions

Melanoma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nausicaa MALISSEN, Doctor

  assistance publique - hôpitaux de Marseille

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clement PIERRE, PhD

CONTACT

+33491435796; clement.pierre@ap-hm.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2026
• First Posted: September 8, 2026
• Study Start (Estimated): June 1, 2027
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): June 1, 2031
• Last Updated: September 8, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share