Relationship Between Pharmacokinetics and Safety of Vismodegib - OPTIVISMO-1

Sponsor

University Hospital, Bordeaux (Other)

Overall Status

Completed

CT.gov ID

NCT03610022

Collaborator

(none)

Enrollment

Location

Arm

32.3

Actual Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Basal Cell Carcinoma Locally Advanced Basal Cell Carcinoma	Drug: Treatment with vismodegib	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 3, 2018

Actual Primary Completion Date :

May 12, 2021

Actual Study Completion Date :

May 12, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patients with BCC and annexial carcinoma Patients with BCC and annexial carcinoma histologically proven under treatment or new patients under vismodegib	Drug: Treatment with vismodegib Vismodegib 150 mg capsules is administered daily with or without food until disease progression or unacceptable toxicity. Patients are followed in the dermatologic unit of Bordeaux University Hospital (Saint André Hospital) every month. At each consultation, clinical and biological datas, and two blood samples are collected just before taking the drug. One sample is for vismodegib quantification (pharmacokinetic protocol), and the other for the determination of alpha-1 glycoprotein acid level

Arm

Intervention/Treatment

Experimental: Patients with BCC and annexial carcinoma

Patients with BCC and annexial carcinoma histologically proven under treatment or new patients under vismodegib

Drug: Treatment with vismodegib

Vismodegib 150 mg capsules is administered daily with or without food until disease progression or unacceptable toxicity. Patients are followed in the dermatologic unit of Bordeaux University Hospital (Saint André Hospital) every month. At each consultation, clinical and biological datas, and two blood samples are collected just before taking the drug. One sample is for vismodegib quantification (pharmacokinetic protocol), and the other for the determination of alpha-1 glycoprotein acid level

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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