Sonidegib for Locally advanced basal cell carcinoma

Inclusion criteria

• {"criterion_text":"- Written, signed informed consent, including consent to photographs of lesions.\n- Per donne in età fertile, test di gravidanza negativo entro 7 giorni dall’inizio della terapia.\n- Participant must agree to not breastfeed during the study and for 20 months after the last dose of study treatment.\n- For male patients with female partners of childbearing potential, agreement to use a condom, even after a vasectomy, during sexual intercourse with female partners while being treated with sonidegib, and for 6 months after the last dose was received.\n- Agreement not to donate blood or blood products during the study and for at least 20 months after the last dose was received.\n- For male patients, agreement not to donate sperm during treatment and for 6 months after the last dose was received.\n- Age ≥ 18 years.\n- Histologic confirmation of locally advanced BCC lesion.\n- Patients with BCCs already in treatment with Hedgehog inhibitor for: •\tBCC that has recurred in the same location after three or more surgical procedures and/or curative resection is deemed unlikely •\tmultifocal BCC or extensive tumours with bleeding or infected areas •\tanticipated substantial morbidity and/or deformity from surgery (e.g. removal of all or part of a facial structure, such as nose, ear, eyelid, eye; or requirement for limb amputation) •\tmultiple BCCs not amenable to surgical treatment because of oncologic or clinical reasons\n- Patient having shown a complete response (CR) to Hedgehog inhibitor within the 3 months prior to the screening. In BCC every effort should be made to obtain histologic confirmation of CR mainly in case of doubt, performing several biopsies in the sites where disease was present. CR must have been confirmed by 2 consecutive radiologic exams and by visual and dermoscopic examinations.\n- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.\n- Adequate hematopoietic capacity, defined as the following: •\tHaemoglobin > 8.5 g/dl •\tAbsolute neutrophil count (ANC) = 1000/mmc •\tPlatelet count = 75,000/mmc\n- Adequate hepatic and renal function, defined as the following: •\tAspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 times the upper limit of normal (ULN), Total bilirubin = 1.5 × ULN or within 3 × ULN for patients with documented Gilbert syndrome •\tCalculated serum creatinine clearance (CrCl) = 30 mL/min\n- For women of childbearing potential, a negative pregnancy test within 7 days prior to commencement of dosing is required"}

Exclusion criteria

• {"criterion_text":"- Metastatic BCC.\n- Inability or unwillingness to swallow capsules.\n- Inability or unwillingness to comply with study procedures.\n- Pregnancy or lactation.\n- Concurrent non–protocol-specified anti-tumour therapy (e.g., chemotherapy, other targeted therapy, radiation therapy, or photodynamic therapy, including participation in an experimental drug study).\n- Uncontrolled medical illness, including advanced malignancies, at the discretion of the Investigator.\n- 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."}

Primary endpoints

• {"endpoint_text":"- Proportion of patients maintaining the tailored treatment with sonidegib 12 months after enrolment into the study.","definition_or_measurement_approach":"Proportion (percentage) of patients who remain on the tailored sonidegib treatment at 12 months after enrolment; endpoint measured as proportion at 12 months as stated."}

Secondary endpoints

• {"endpoint_text":"- Compliance with the study treatment (number of sonidegib cps assumed/number of sonidegib cps foreseen during the study period).","definition_or_measurement_approach":"Measured as number of sonidegib capsules taken divided by number of capsules expected during the study period."}
• {"endpoint_text":"- Proportion of patients maintaining treatment 2 years after achieving CR.","definition_or_measurement_approach":"Proportion (percentage) of patients still on treatment two years after achieving complete response."}
• {"endpoint_text":"- Proportion of patients who experimented relapses after sonidegib interruption for causes other than disease progression at 1 year after achieving CR.","definition_or_measurement_approach":"Proportion (percentage) of patients with relapse within 1 year after treatment interruption for non-progression causes."}
• {"endpoint_text":"- Proportion of patients who experimented relapse after sonidegib interruption for causes other than disease progression at 2 years after achieving CR.","definition_or_measurement_approach":"Proportion (percentage) of patients with relapse within 2 years after treatment interruption for non-progression causes (relapse-free survival assessment)."}
• {"endpoint_text":"- Safety of the tailored sonidegib schedules (schedule 1: 14 days on - 14 days off; schedule 2: 7 days on – 21 days off) measured by CTCAE scale. AEs and SAEs will be described as number of events and percentages, stratified for grade.","definition_or_measurement_approach":"Adverse events and serious adverse events will be recorded and graded by CTCAE v5.0; reported as counts and percentages stratified by grade for each schedule."}
• {"endpoint_text":"- Quality of life measured by monthly ESAS (Edmonton Symptom Assessment System scales. The QoL scores for each domain and the overall QoL will be described and possible significant predictors of the QoL scores will be analysed using the Chi-square test or the Wilcoxon t test, when appropriate.","definition_or_measurement_approach":"Monthly ESAS scores per domain and overall QoL will be described; statistical analyses (Chi-square or Wilcoxon t-test) to assess predictors where appropriate."}
• {"endpoint_text":"- Use of concomitant medication and use of medical resources to manage toxicities caused by the study drug (e.g., general practitioner’s consultation, other medical visits, etc). Number of drugs and access to medical visits will be registered for descriptive purposes.","definition_or_measurement_approach":"Descriptive recording of concomitant medications and medical resource use (number of drugs, number of medical visits) related to toxicity management."}
• {"endpoint_text":"- Dermoscopic Evaluation: Dermoscopic images of the lesion area will be obtained using a videodermatoscope. Changes during treatment period will be described and correlate with drug response.","definition_or_measurement_approach":"Dermoscopic images obtained with videodermatoscope; changes described and correlated with clinical response."}
• {"endpoint_text":"- Translational analysis: characteristics of mutation in Hh pathway genes of BCC pre and post-treatment and evaluation of microenvironment in naive and pre-treated BCC.","definition_or_measurement_approach":"Molecular characterization of Hedgehog pathway gene mutations pre- and post-treatment and microenvironment evaluation in naive and pre-treated BCC samples (translational research)."}

Italy

Earliest CTIS Part Ii Submission Date

13-08-2024

Latest Decision Or Authorization Date

14-07-2025

Processing Time Days

335

Number Of Sites

10

Number Of Participants

21

Primary sponsor

Full Name

Fondazione GONO Plus

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"Sun Pharmaceutical Industries Europe B.V.","duties_or_roles":"Source of monetary support","organisation_type":""}