Patients with large and/or recurrent resectable basal cell carcinoma MedDRA version: 20.0 Level: PT Classification code 10004146 Term: Basal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Erivedge®
Product Name: Vismodegib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: VISMODEGIB
CAS Number: 879085-55-9
Other descriptive name: VISMODEGIB
Concentration unit: mg mill
Sponsors
SRH Wald-Klinikum Gera GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patient aged = 18 years 2. Able to participate and willing to give written informed consent including consent for photographs prior to performance of study-related procedures and to comply with the study protocol. 3. Patients with at least 1 large (= 2 cm in diameter in head/neck region, = 5 cm for trunk/extremities) basal cell carcinoma (BCC), still resectable, but with increased risk for cosmetic disfigurement or functional defects by assessment of the enrolling physician. Patients with large (as defined above) recurrent basal cell carcinoma are also eligible. 4. Patients must be naïve to treatment with vismodegib or other hedgehog pathway inhibitors 5. Local histopathologic confirmation of BCC (3 mm punch biopsy) 6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 7. Consent to undergo mapping biopsies upon reaching complete response 8. Adequate hematologic and organ function, defined by the following laboratory results, to be obtained within 7 days prior to registration and prior to first dose of study drug treatment: • Absolute neutrophilic count > 1,0 x 109/L • Platelet count = 75 x 109/L • Hemoglobin = 8,5 g/dL • Albumin = 2.5 g/dL • Bilirubin = 1.5 x the upper limit of normal (ULN) or within 3 x ULN for patients with documented Gilbert syndrome • AST, ALT, and AP = 3 x ULN • Serum creatinine = 1.5 x ULN 9. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use 2 effective forms of contraception during the course of this study. Females have to continue to always use 2 effective forms of contraception for at least 24 months after completion of study therapy, and males for at least 2 months after end of therapy. Breast feeding is likewise not allowed for at least 24 months after completion of study therapy. • Females of childbearing potential are defined as sexually mature women without prior hysterectomy and who have had menses within the last 12 months. • Females are considered NOT to be of childbearing potential if amenorrheic for >12 months and follicle-stimulating hormone (FSH) level = 40 IU/L. • Females who are amenorrheic = 2 years, FSH requirement are waived. • Effective forms of contraception includes surgical sterilization, a reliable barrier method with spermicidal, birth control pills, or contraceptive hormone implants • Female patients of childbearing potential who desire to have children in the future should be informed about measures regarding conservation of fertility 10. Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential (including pre-menopausal women with tubal ligation). 11. Absence of any psychological, familial, sociological, or geographical condition that potentially hampers compliance with the study protocol and follow-up as defined by the treatment discontinuation schedule. 12. Agreement not to donate blood or blood products during the study and for at least 24 months after discontinuation of vismodegib. Because vismodegib has been detected in seminal fluid, in addition for men, agreement not donate sperm during the study or for at least 2 months after discontinuation of therapy. 13. Optional: Consent to undergo non-invasive imaging examinations by means of confocal laserscan-microscopy (CLSM) and/or optical coherence tomography (OCT), during and after end of study treatment. Are the trial subjects under 18? no Number of subjects for this age ra
Exclusion criteria
Exclusion criteria: 1. History of prior treatment with vismodegib or any other hedgehog pathway inhibitor. 2. Radiotherapy that involved the field of the target lesion(s) within 6 months prior to registration. Only one radiotherapy of the target lesion(s) performed > 6 months prior to registration is allowed. If a second radiotherapy in this field took place, patient will be excluded. 3. Any metastatic BCC 4. Metatypic BCC 5. Known or suspected Gorlin-Goltz syndrome 6. Uncontrolled medical illness, including advanced malignancies (no activities of the malignancies in the past 3 years), at the discretion of the Investigator 7. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications 8. History or current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances 9. Any medical or psychological illness or condition preventing adequate consent or ability to comply with the protocol 10. Inability or unwillingness to swallow capsules 11. Inability or unwillingness to comply with study and follow-up procedures 12. Current severe, uncontrolled systemic disease 13. History of malabsorption or other conditions that would interfere with the absorption of the orally applicated study drug 14. Pregnant, lactating, or breast feeding women 15. Patients with one of the following rare hereditary conditions: galactose intolerance, primary hypolactasia, or glucose-galactose malabsorption 16. Participation in another clinical drug study within 28 days before registration 17. Known or suspected alcohol or drug abuse in the opinion of the investigator 18. Known hypersensitivity reaction to vismodegib or any of the other ingredients of this medicine 19. Treatment with St John’s wort (Hypericum perforatum)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives for this study are as follows: • To evaluate the disease control rate (DCR) defined as CR, PR, or SD after 12 weeks of treatment with vismodegib in the neoadjuvant treatment setting • To assess the objective and relative (%) reduction of the involved skin surface after 12 weeks of treatment with vismodegib (involved skin surface intended for excision at baseline versus surface of the finally excised specimen) ;Secondary Objective: • To evaluate the DCR (CR, PR, or SD) after 12 weeks of treatment with vismodegib in the neoadjuvant treatment setting for different basal cell carcinoma histotypes (superficial, scleroderma, nodular, others) • To assess the duration of overall response (DoR) • To characterize the toxicity and tolerability profile in patients receiving vismodegib in the neoadjuvant setting. • To evaluate health-related quality of life in patients receiving vismodegib for neoadjuvant treatment of basal cell carcinoma as measured by the Skindex-16 • To explore the diagnostic suitability of non-invasive imaging techniques (in vivo confocal laserscan-microscopy (CLSM) and/or optical coherence tomography (OCT)) for the evaluation of response status of patients receiving vismodegib in the neoadjuvant setting;Primary end point(s): • the evaluation of disease control rate (DCR) after 12 weeks of treatment with vismodegib in the neoadjuvant treatment setting. • the assessment of the objective and relative (%) reduction of the involved skin surface after 12 weeks of treatment with vismodegib (involved skin surface intended for excision at baseline versus surface of the finally excised specimen);Timepoint(s) of evaluation of this end point: after 12 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • DCR (CR + PR + SD) after 12 weeks of treatment with vismodegib in the neoadjuvant treatment setting for different basal cell carcinoma histotypes (superficial, scleroderma, nodular, others) • Duration of overall response • Safety and tolerability Safety variables to be analysed during the treatment period include: ? ECOG ? Incidence, type, and severity of AEs ? Incidence and nature of serious adverse events (SAEs) ? Incidence of AEs leading to vismodegib discontinuation or interruption ? Adherence to the treatment, measured by number of patients discontinuing the treatment (for any reason) and treatment interruptions • Health-related quality of life assessed by using the Skindex-16 questionnaire • Correlation of the efficacy by means of non-invasive imaging techniques (CLSM or OCT): o Objective (in mm) and relative (%) reduction of the BCC-involved skin and resection area before and after vismodegib treatment o Deviation (in %) between histopathology of punch biopsies and non-invasive imaging techniques ;Timepoint(s) of evaluation of this end point: • DCR (CR + PR + SD): after 12 weeks of treatment • All other endpoints: during the whole study | — |
Countries
Germany
Contacts
Public ContactPD Dr. med. habil. Martin Kaatz
SRH Wald-Klinikum Gera GmbH
Outcome results
None listed