Relationship Between Pharmacokinetics and Safety of Vismodegib - OPTIVISMO-1
Nyckelord
Abstrakt
Beskrivning
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.
Datum
| Senast verifierad: | 01/31/2020 |
| Först skickat: | 07/02/2018 |
| Beräknad anmälan inlämnad: | 07/24/2018 |
| Först publicerad: | 07/31/2018 |
| Senaste uppdatering skickad: | 02/04/2020 |
| Senaste uppdatering publicerad: | 02/06/2020 |
| Faktiskt startdatum för studien: | 09/02/2018 |
| Uppskattat primärt slutdatum: | 10/31/2020 |
| Beräknat slutfört datum: | 10/31/2020 |
Tillstånd eller sjukdom
Intervention / behandling
Drug: Patients with BCC and annexial carcinoma
Fas
Armgrupper
| Ärm | Intervention / behandling |
|---|---|
| Experimental: Patients with BCC and annexial carcinoma Patients with BCC and annexial carcinoma histologically proven under treatment or new patients under vismodegib | Drug: Patients with BCC and annexial carcinoma 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 |
Urvalskriterier
| Åldrar berättigade till studier | 18 Years Till 18 Years |
| Kön som är berättigade till studier | All |
| Accepterar friska volontärer | Ja |
| Kriterier | 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 |
Resultat
Primära resultatåtgärder
1. Serious side effects (grade 2 or more) during the clinical response follow-up to vismodegib [Occurrence from inclusion to 6 months visit]
Sekundära resultatåtgärder
1. Relationship between the plasma concentrations of free and/or total vismodegib, and covariates [From inclusion to 6 months visit]
2. Clinical response to vismodegib in term of efficacy [at least at each visit, from inclusion to 6 months visit]
