Study of the Relationship Between the Pharmacokinetics of Vismodegib and Safety Data: a Pilot Study to Therapeutic Optimization in Patients With Basal Cell Carcinoma - OPTIVISMO-1

In patients treated with the Hedgehog (Hh) signaling pathway inhibitor, vismodegib, for Basal Cell Carcinoma (BCC), intolerance to this drug is a cause of non-compliance to treatment and often requires therapy discontinuation in spite of its potent anticarcinomic action. Indeed, vismodegib, at the standard dose of 150 mg/day, leads to many heavy side effects often 1 month after therapy initiation. The major side effects are daily or multiple daily cramps (associated with hypometabolism) in 60% of patients, dysgeusia, ageusia and alopecia (related to stem cells), and tiredness. Currently, there is no recommendation for dose adjustment against the occurrence of these adverse effects, so that clinicians propose temporary or definitive therapeutic discontinuation for around 30% of patients. The management of these therapeutic pauses is a challenge for clinicians, as no data are available on their impact on treatment long-term response. We hypothesize that vismodegib side effects are related to high plasma concentrations of drug in many patients. To date, there is no data from phase 3 study, sparse pharmacokinetic data emanating from Phase 1 and 2 studies in various solid tumors.

Patients included are treated with vismodegib (Hedgehog (Hh) pathway inhibitor) for symptomatic metastatic BCC, or for advanced BCC when surgery and radiotherapy are not appropriate. Included patients are new patients initiating a treatment with vismodegib or patients already on vismodegib. The study of the relationship between plasma concentrations of vismodegib and tolerance, requires at each monthly follow-up visits, monitoring of: concentrations of free (unbound to the α1-GPA) and total (bound and unbound) forms of vismodegib, α1-GPA plasma concentrations, patient's status, data on safety and efficacy, and clinical and biological data (covariates that may modulate the vismodegib pharmacokinetics resulting in increased plasma concentrations). Patients will be followed for 6 months.