Clinical trial NCT02667574: Study Evaluating the Interest of Vismodegib as Neo-adjuvant Treatment of Basal Cell Carcinoma (BCC)
Official title: Phase II Study Evaluating the Interest of Vismodegib as Neo-adjuvant Treatment of Basal Cell Carcinoma (BCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Basal Cell Carcinoma
Keywords: basal cell carcinoma
surgery
stage
vismodegib
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2016-01-29
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Open-label, non-comparative, multicenter, phase II study of Vismodegib in patients with locally advanced BCC.

Detailed description: Enrolled patients will receive continuous once-daily oral dosing of Vismodegib at a dosage of 150 mg (in accordance with the product SmPC) per administration. One cycle of therapy will be defined as 28 days of treatment. The treatment will be renewed once a month depending on the product tolerance.

The trial will consist of a Screening Period (Day -28 to -1), a Treatment Period (Day 1 to BOR), one End of Treatment Visit, one Surgery Visit and 8 Safety Follow-Up Visits after the last dose of Vismodegib (+/- 5 days). Day 1 of the study will be defined as the first day a patient receives Vismodegib.

Eligibility criteria: Inclusion Criteria:

1. Patients with BCC, which surgery stage is A, B or C (cf. Appendix 3: Definition of surgery stages), with a diameter ≥ 3cm in zones at intermediate risk of tumor recurrence and a BCC with a diameter of ≥ 2 cm in the zones at higher risk of tumor recurrence. According to the HAS recommendations, two zones are taken into consideration:

   * Zones at intermediate risk of tumor recurrence: forehead, cheek, chin, neck and scalp
   * Zones at higher risk of tumor recurrence: nose and periorificial sites of the cephalic extremity
2. The decision to include the patient in this study should be taken during the Pluridisciplinary Committee Meeting (RCP). During this RCP, the radiotherapy should be considered as an inadequate treatment. (If the radiotherapist is absent during the meeting, his opinion should be documented in the patient's medical record).
3. Written informed consent
4. Age ≥ 18 years old
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0, 1, or 2
6. At least one histologically confirmed lesion...
7. Patients with Gorlin syndrome may enroll in this study but must meet the other inclusion criteria
8. Patients with measurable and/or non-measurable disease (as defined by RECIST, v1.1)
9. Adequate organ function, as evidenced by the following laboratory results:

   * Hemoglobin \> 8.5 g/dL
   * Granulocyte count ≥ 1000/μL
   * Platelet count ≥ 75,000/μL
   * Aspartate transaminase (AST ) and alanine transaminase (ALT) ≤ 3 × upper limit of normal (ULN)
   * Total bilirubin ≤ 1.5 × ULN or within 3 × ULN for patients with documented Gilbert syndrome
10. Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥ 1 year.
11. Women of childbearing potential must use one highly-effective method of contraception and one barrier method of contraception during treatment and for 24 months after the final dose. Highly-effective methods of contraception are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (e.g., implants, injectables, or intra-uterine devices; refer to Appendix 8 for more details). At the discretion of the Investigator, acceptable methods of contraception may include total abstinence. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, and postovulation methods\] and withdrawal are not acceptable methods of contraception.).
12. For male patients with female partners of childbearing potential, agreement top use a condom with spermicide, even after vasectomy, during sexual intercourse with partners while being treated with Vismodegib and for two months after completion of study treatment
13. For male patients, agreement not to donate semen during the study and for 24 months after discontinuation of Vismodegib
14. Agreement not to donate blood or blood products during the study and for at least 24 months after discontinuation of Vismodegib.
15. Life expectancy \> 12 weeks
16. Patients covered by a Health Insurance System

Exclusion Criteria:

1. Inability or unwillingness to swallow capsules
2. Patients with BCC situated out of the head or the neck area
3. Pregnancy or lactation
4. Concurrent non-protocol-specified anti-tumor therapy (e.g., chemotherapy, other targeted therapy or photodynamic therapy
5. Chemotherapy within 4 weeks prior to enrollment
6. Participation in another clinical trial within 4 weeks prior to enrollment
7. Radiotherapy within 6 months prior to enrolment
8. Metastatic BCC
9. Uncontrolled medical illnesses such as infection requiring treatment with intravenous antibiotics.
10. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or that renders the patient at high risk from treatment complications.
11. Patients with a rare hereditary problem of galactose intolerance, primary hypolactasia or glucose-galactose malabsorption (according to the product SmPC).
12. Patients unable or unwilling to comply with the protocol requirements
13. Patients in emergency situations
14. Patients kept in detention

Primary outcomes:
measure: the change in surgery stages
timeFrame: Between baseline and maximum 10 months of treatment
Secondary outcomes:
measure: Number of patients with locally advanced BCC with down-staging of surgical procedures with Vismodegib
timeFrame: from 4 to 10 months of treatment
measure: Gravity index related to the surgical or functional results (global score)
timeFrame: At maximum 10 months of treatment
measure: Score of the clinical benefits at BOR
timeFrame: At maximum 10 months of treatment
measure: Assessment of treatment toxicity according to NCI-CTC, v4.0
timeFrame: 2 months after the surgery and maximum 12 months after the Vismodegib initiation
measure: Quality of life assessment by Skindex-16 questionnaire
timeFrame: At screening, at 3 months, at 6 months of treatment
measure: the tumor recurrence rate
timeFrame: at 3 years of follow-up
measure: the cytological response by biopsy
timeFrame: from 4 to 10 months of treatment
Other outcomes:
Locations:
city: Besançon
country: France
facility: CHU de Besançon
city: Bordeaux
country: France
facility: Hôpital St André
city: Boulogne sur mer
country: France
facility: CH de Boulogne sur mer
city: Clermont-Ferrand
country: France
facility: CHU - Hôpital d'Estaing
city: Dijon
country: France
facility: CHU Bocage
city: Lille
country: France
facility: Clinique de Dermatologie
city: Marseille
country: France
facility: Hôpital de la Timone
city: Montpellier
country: France
facility: Hôpital Saint Eloi
city: Paris
country: France
facility: Hôpital Bichat
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: CHU Ambroise Paré
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
city: Pierre-benite
country: France
facility: Centre hospitalier Lyon Sud
city: Reims
country: France
facility: Hôpital Robert Debré
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Vandoeuvre Les Nancy
country: France
facility: Hôpitaux de Brabois
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: University Hospital, Lille
name: Laurent MORTIER, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: