- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03610022
Relationship Between Pharmacokinetics and Safety of Vismodegib - OPTIVISMO-1 (OPTIVISMO-1)
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
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
-
Bordeaux, France
- CHU de Bordeaux
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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
|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serious side effects (grade 2 or more) during the clinical response follow-up to vismodegib
Time Frame: 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)
|
Occurrence from inclusion to 6 months visit
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Relationship between the plasma concentrations of free and/or total vismodegib, and covariates
Time Frame: From inclusion to 6 months visit
|
From inclusion to 6 months visit
|
|
Clinical response to vismodegib in term of efficacy
Time Frame: 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
|
at least at each visit, from inclusion to 6 months visit
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CHUBX 2017/41
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Locally Advanced Basal Cell Carcinoma
-
Thomas Jefferson UniversityRecruitingLocally Advanced Basal Cell CarcinomaUnited States
-
Gruppo Oncologico del Nord-OvestRecruitingLocally Advanced Basal Cell CarcinomaItaly
-
Sue YomGenentech, Inc.CompletedSkin Cancer | Locally Advanced Basal Cell Carcinoma | Cutaneous MalignancyUnited States
-
Emory UniversityAstex Pharmaceuticals, Inc.RecruitingHead and Neck Carcinoma of Unknown Primary | Locally Advanced Head and Neck Squamous Cell Carcinoma | Locally Advanced Hypopharyngeal Squamous Cell Carcinoma | Locally Advanced Laryngeal Squamous Cell Carcinoma | Locally Advanced Nasopharyngeal Squamous Cell Carcinoma | Locally Advanced Oropharyngeal...United States
-
Novartis PharmaceuticalsCompletedAdvanced Solid Tumors | Recurrent or Refractory Medulloblastoma | Locally Advanced or Metastatic Basal Cell CarcinomaUnited States, United Kingdom, Switzerland, Netherlands
-
Memorial Sloan Kettering Cancer CenterRecruitingSkin Cancer | Squamous Cell Carcinoma | Cutaneous Squamous Cell Carcinoma | Locally Advanced Skin Squamous Cell Carcinoma | Locally Advanced Cutaneous Squamous Cell Carcinoma | Locally Advanced Squamous Cell Carcinoma | Locally Advanced Squamous Cell Carcinoma of the SkinUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingMetastatic Bladder Urothelial Carcinoma | Metastatic Renal Pelvis Urothelial Carcinoma | Metastatic Ureter Urothelial Carcinoma | Metastatic Urethral Urothelial Carcinoma | Metastatic Urothelial Carcinoma | Locally Advanced Bladder Urothelial Carcinoma | Locally Advanced Renal Pelvis Urothelial... and other conditionsUnited States
-
H. Lee Moffitt Cancer Center and Research InstituteGenentech, Inc.RecruitingAdvanced Basal Cell CarcinomaUnited States
-
Mayo ClinicNot yet recruitingMetastatic Lung Non-Small Cell Carcinoma | Metastatic Clear Cell Renal Cell Carcinoma | Resectable Lung Non-Small Cell Carcinoma | Metastatic Malignant Solid Neoplasm | Metastatic Bladder Urothelial Carcinoma | Metastatic Colorectal Carcinoma | Metastatic Triple-Negative Breast Carcinoma | Locally... and other conditionsUnited States
-
Millennium Pharmaceuticals, Inc.CompletedCarcinoma, Basal Cell | Advanced Nonhematologic MalignanciesUnited States
Clinical Trials on Treatment with vismodegib
-
Genentech, Inc.Completed
-
University of Michigan Rogel Cancer CenterCompletedCarcinoma, Basal CellUnited States
-
Genentech, Inc.Completed
-
Hoffmann-La RocheCompletedBasal Cell CarcinomaItaly, Czechia, Hungary, Belgium, Canada, Ireland, Mexico, Portugal, Slovenia, Spain, Turkey, Brazil, Bosnia and Herzegovina, Romania, United Kingdom, Germany, Israel, France, Greece, Russian Federation, Lithuania, Netherlands, Norway, Colomb... and more
-
Sidney Kimmel Comprehensive Cancer Center at Johns...CompletedProstate CancerUnited States
-
SRH Wald-Klinikum Gera GmbHCompletedBasal Cell CarcinomaGermany
-
University Hospital, LilleHoffmann-La RocheCompletedBasal Cell CarcinomaFrance
-
University of ArizonaGenentech, Inc.CompletedBasal Cell CarcinomaUnited States
-
Hoffmann-La RocheTerminatedBasal Cell CarcinomaUnited States
-
Hoffmann-La RocheWithdrawnIdiopathic Pulmonary Fibrosis