Relationship Between Pharmacokinetics and Safety of Vismodegib - OPTIVISMO-1

Phase 4

Completed

• Conditions: Metastatic Basal Cell Carcinoma; Locally Advanced Basal Cell Carcinoma
• Interventions: Drug: Treatment with vismodegib

• Registration Number: NCT03610022
• Lead Sponsor: University Hospital, Bordeaux

Brief Summary

Vismodegib (ERIVEDGE®) at the standard dose of 150 mg/day orally is indicated for the treatment of advanced Basal Cell Carcinoma (BCC) and is associated with many adverse effects. Cramps, alopecia, dysgeusia, weight loss and others observed in clinical practice, compromize compliance and often lead to treatment discontinuation. Currently, it is the only drug available in this indication. Our main objective is to assess the relationship between plasma concentrations of vismodegib, and the occurrence of adverse effects within 6 months of inclusion in the study.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2018-07-03
• Study First Submitted QC: 2018-07-25
• Study First Posted: 2018-08-01
• Study Start: 2018-09-03
• Primary Completion: 2021-05-12
• Study Completion: 2021-05-12
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-17
• Last Update Posted: 2022-08-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

• Patients with BCC and annexial carcinoma histologically proven under treatment or new patients under vismodegib or patients who restarted treatment
• 18 years-old or older
• Complete medical record
• Members or beneficiaries of a social security system,
• Patients must have given informed consent, free and written.

Exclusion Criteria

• Patients with or without BCC and not treated with vismodegib
• BCC patients who stopped treatment with vismodegib due to non-response or progression on treatment
• Patients under 18 years-old
• Patients whose medical record is incomplete
• Unaffiliated subjects or not beneficiaries of a security system social,
• Patients who have not been informed and have not given their consent, free and written,
• Pregnant and childbearing women without effective contraceptive method
• Patients with confusional state

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients with BCC and annexial carcinoma	Treatment with vismodegib	Patients with BCC and annexial carcinoma histologically proven under treatment or new patients under vismodegib

Primary Outcome Measures

Name	Time	Method
Serious side effects (grade 2 or more) during the clinical response follow-up to vismodegib	Occurrence from inclusion to 6 months visit	Patients already on vismodegib will be monitored at inclusion and for 6 months (M0, M1, M2, M3, M4, M5). New patients will be monitored from the end of the first month after inclusion and during 6 months (M1, M2, M3, M4, M5, M6)

Secondary Outcome Measures

Name	Time	Method
Relationship between the plasma concentrations of free and/or total vismodegib, and covariates	From inclusion to 6 months visit
Clinical response to vismodegib in term of efficacy	at least at each visit, from inclusion to 6 months visit	Classification into 4 categories: progression, stabilité, partial response and complete response according to RECIST criteria

Trial Locations

Locations (1)

Chu de Bordeaux; 🇫🇷 Bordeaux, France