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Relationship Between Pharmacokinetics and Safety of Vismodegib - OPTIVISMO-1 (OPTIVISMO-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03610022
Recruitment Status : Recruiting
First Posted : August 1, 2018
Last Update Posted : February 7, 2020
Information provided by (Responsible Party):
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.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
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 : September 3, 2018
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Vismodegib

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

Primary Outcome Measures :
  1. 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)

Secondary Outcome Measures :
  1. Relationship between the plasma concentrations of free and/or total vismodegib, and covariates [ Time Frame: From inclusion to 6 months visit ]
  2. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03610022

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Contact: Marie BEYLOT-BARRY, PU-PH +33 5 57 82 25 00
Contact: Benjamin SOURISSEAU

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Chu de Bordeaux Recruiting
Bordeaux, France
Contact: Marie BEYLOT-BARRY   
Contact: Benjamin SOURISSEAU   
Sponsors and Collaborators
University Hospital, Bordeaux

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Responsible Party: University Hospital, Bordeaux Identifier: NCT03610022    
Other Study ID Numbers: CHUBX 2017/41
First Posted: August 1, 2018    Key Record Dates
Last Update Posted: February 7, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Bordeaux:
Human plasma concentrations
Adverse events
Additional relevant MeSH terms:
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Carcinoma, Basal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Basal Cell