Phase II Open-Label Study on Sonidegib Compliance in Locally Advanced Basal Cell Carcinoma Patients with Complete Response

Trial ID: 2024-516797-29-00
Sponsor: Fondazione GONO Plus

Trial statistics

science

test molecule

location_city

research sites

public

country

medical_information

disease

person_search

investigators

Diseases & Conditions

Basal cell carcinoma

Objectives

The primary objective of this study is to evaluate the **compliance** to a tailored regimen of sonidegib in patients with locally advanced basal cell carcinoma who have previously achieved complete response (CR) with any inhibitor of the Hedgehog pathway. This is clinically relevant as it aims to optimize treatment adherence, potentially improving patient outcomes and reducing the risk of disease recurrence.

Secondary objectives include:

Assessing the compliance with the study treatment.
Evaluating the proportion of patients maintaining sonidegib treatment two years after achieving CR.
Evaluating the proportion of patients experiencing relapse-free survival (RFS) after sonidegib interruption for reasons other than disease progression.
Evaluating the safety of sonidegib tailored regimens, measured by the CTCAE v 5.0 scale.
Assessing the quality of life using the ESAS scale.
Assessing the use of concomitant medication and medical resources to manage toxicities caused by the study drug.
Conducting dermoscopic evaluation to collect the most common characteristics of basal cell carcinoma at baseline and during the treatment period.
Conducting translational research to evaluate changes in the molecular pattern of basal cell carcinoma after achieving complete response and in the microenvironment in naive and pre-treated basal cell carcinoma.

Participants

The clinical trial involves participants diagnosed with **locally advanced basal cell carcinoma**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a histologic confirmation of the condition and must have shown a complete response to a Hedgehog inhibitor within the three months prior to screening. The trial does not include a vulnerable population. Participants are expected to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, indicating they are fully active or capable of self-care. Adequate hematopoietic, hepatic, and renal functions are necessary for inclusion. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as agreement not to donate blood or sperm during and after the study, and for women of childbearing potential, a negative pregnancy test is required prior to dosing. The trial population was selected based on these criteria to ensure the safety and efficacy of the tailored regimen of sonidegib being evaluated.

Plans and Procedures

The clinical trial is a **phase II, open-label study** designed to evaluate the compliance to a tailored regimen of **sonidegib** in patients with **locally advanced basal cell carcinoma** who have previously achieved a complete response (CR) with any Hedgehog pathway inhibitor. The trial aims to assess the proportion of patients maintaining the tailored treatment with sonidegib 12 months after enrollment. Secondary endpoints include compliance with the study treatment, the proportion of patients maintaining treatment two years after achieving CR, and the safety of the tailored sonidegib schedules. The study will also evaluate the quality of life and use of concomitant medication.

The trial is expected to last until December 22, 2026, with recruitment having started on January 26, 2021. Participants will be involved in the study for a maximum treatment period of 24 months. The study involves oral administration of Odomzo 200 mg hard capsules, with a maximum daily dose of 200 mg. The trial includes a sequence of study visits, starting with an inclusion (screening) visit to confirm eligibility based on criteria such as age, histologic confirmation of the condition, and adequate hematopoietic, hepatic, and renal function. Follow-up visits will be conducted to monitor compliance, safety, and efficacy, with the end-of-study visit marking the conclusion of the participant's involvement.

Participants may be terminated early from the study if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The study is not categorized as low intervention and involves an EMA-approved drug. The trial design does not include randomization or blinding, as it is an open-label study. The primary objective is to improve compliance and treatment duration through a tailored schedule of sonidegib, with the ultimate goal of maintaining CR in patients with locally advanced basal cell carcinoma.

Treatment

The clinical trial involves the administration of **Odomzo 200 mg hard capsules**, which contain the active substance **sonidegib**. Sonidegib is a chemically derived compound classified under the ATC code L01XJ02. The pharmaceutical form of the medication is a hard capsule, designed for oral administration. Each capsule contains 200 mg of sonidegib, and the maximum daily dose is set at 200 mg. The treatment period for participants is capped at 24 months. The medication is manufactured by Sun Pharmaceutical Industries Europe B.V. and is not formulated for pediatric use. The trial aims to evaluate compliance with a tailored regimen of sonidegib in patients with locally advanced basal cell carcinoma who have previously achieved a complete response with any Hedgehog pathway inhibitor.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of the experimental medication, Odomzo. Participants' compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is open-label, meaning both the researchers and participants are aware of the treatment being administered. The primary objective is to assess the compliance and duration of treatment with sonidegib in the specified patient population.

Efficacy

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of patients maintaining the tailored treatment with **sonidegib** 12 months after enrollment into the study. Secondary endpoints include compliance with the study treatment, measured by the number of sonidegib capsules taken compared to the number foreseen during the study period, and the proportion of patients maintaining treatment 2 years after achieving complete response (CR). Additionally, the trial will evaluate the proportion of patients experiencing relapses after sonidegib interruption for reasons other than disease progression at 1 and 2 years post-CR.

Safety and quality of life are also key components of the efficacy assessment. Safety will be measured using the CTCAE scale, with adverse events (AEs) and serious adverse events (SAEs) described by the number of events and percentages, stratified by grade. Quality of life will be assessed monthly using the Edmonton Symptom Assessment System (ESAS) scales, with scores analyzed for significant predictors using statistical tests such as the Chi-square test or the Wilcoxon t-test. Additional assessments include the use of concomitant medication and medical resources to manage toxicities, dermoscopic evaluation using a videodermatoscope to correlate changes with drug response, and translational analysis of mutation characteristics in Hedgehog pathway genes of basal cell carcinoma (BCC) pre- and post-treatment.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Written, signed informed consent, including consent to photographs of lesions.
Age ≥ 18 years.
Histologic confirmation of locally advanced BCC lesion.
Patients with BCCs already in treatment with Hedgehog inhibitor for: • BCC that has recurred in the same location after three or more surgical procedures and/or curative resection is deemed unlikely • multifocal BCC or extensive tumours with bleeding or infected areas • anticipated 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) • multiple BCCs not amenable to surgical treatment because of oncologic or clinical reasons
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.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Adequate hematopoietic capacity, defined as the following: • Haemoglobin > 8.5 g/dl • Absolute neutrophil count (ANC) = 1000/mmc • Platelet count = 75,000/mmc
Adequate hepatic and renal function, defined as the following: • Aspartate 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 • Calculated serum creatinine clearance (CrCl) = 30 mL/min
For women of childbearing potential, a negative pregnancy test within 7 days prior to commencement of dosing is required
Per donne in età fertile, test di gravidanza negativo entro 7 giorni dall’inizio della terapia.
Participant must agree to not breastfeed during the study and for 20 months after the last dose of study treatment.
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.
Agreement not to donate blood or blood products during the study and for at least 20 months after the last dose was received.
For male patients, agreement not to donate sperm during treatment and for 6 months after the last dose was received.

cancel

Exclusion Criteria

Metastatic BCC.
Inability or unwillingness to swallow capsules.
Inability or unwillingness to comply with study procedures.
Pregnancy or lactation.
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).
Uncontrolled medical illness, including advanced malignancies, at the discretion of the Investigator.
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.