A phase II, open-label study improving compliance and time of treatment after obtaining complete response through a tailored schedule of sonidegib in locally advanced basal cell carcinomas (BCC) – the SONIBEC trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione GONO Plus

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Jan 2021 → ongoing

Decision date (initial)

2024-10-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Sun Pharmaceutical Industries Europe B.V.

External identifiers

EU CT number

2024-516797-29-00

EudraCT number

2020-002613-17

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To evaluate the compliance to a tailored regimen of sonidegib in patients who have previously obtained CR assuming any inhibitor of the Hedgehog pathway.

Secondary objectives 8

1. To assess the compliance with the study treatment.
2. To evaluate the proportion of patients maintaining sonidegib treatment 2 years after achieving CR.
3. To evaluate the proportion of patients who experimented relapse free survival (RFS) after sonidegib interruption for causes other than disease progression.
4. To evaluate the safety of sonidegib tailored regimens (measured by CTCAE v 5.0 scale).
5. To assess the quality of life (ESAS scale).
6. To assess the use of concomitant medication and use of medical resources to manage toxicities caused by the study drug.
7. Dermoscopic Evaluation: to collect the most common characteristics of BCC at baseline and during treatment period.
8. Translational research: to evaluate the changes in molecular pattern of BCC after achieving complete response and in microenvironment in naive and pre-treated BCC.

Conditions and MedDRA coding

locally advanced basal cell carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Written, signed informed consent, including consent to photographs of lesions.
2. Age ≥ 18 years.
3. Histologic confirmation of locally advanced BCC lesion.
4. 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
5. 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
7. Adequate hematopoietic capacity, defined as the following: • Haemoglobin > 8.5 g/dl • Absolute neutrophil count (ANC) = 1000/mmc • Platelet count = 75,000/mmc
8. 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
9. For women of childbearing potential, a negative pregnancy test within 7 days prior to commencement of dosing is required
10. Per donne in età fertile, test di gravidanza negativo entro 7 giorni dall’inizio della terapia.
11. Participant must agree to not breastfeed during the study and for 20 months after the last dose of study treatment.
12. 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.
13. Agreement not to donate blood or blood products during the study and for at least 20 months after the last dose was received.
14. For male patients, agreement not to donate sperm during treatment and for 6 months after the last dose was received.

Exclusion criteria 7

1. Metastatic BCC.
2. Inability or unwillingness to swallow capsules.
3. Inability or unwillingness to comply with study procedures.
4. Pregnancy or lactation.
5. 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).
6. Uncontrolled medical illness, including advanced malignancies, 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients maintaining the tailored treatment with sonidegib 12 months after enrolment into the study.

Secondary endpoints 9

1. Compliance with the study treatment (number of sonidegib cps assumed/number of sonidegib cps foreseen during the study period).
2. Proportion of patients maintaining treatment 2 years after achieving CR.
3. Proportion of patients who experimented relapses after sonidegib interruption for causes other than disease progression at 1 year after achieving CR.
4. Proportion of patients who experimented relapse after sonidegib interruption for causes other than disease progression at 2 years after achieving CR.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione GONO Plus

Sponsor organisation

Fondazione GONO Plus

Address

Interno 11, Via Cesarea 8 Via Cesarea 8

City

Genoa

Postcode

16121

Country

Italy

Scientific contact point

Organisation

Fondazione GONO Plus

Contact name

Paolo Bossi

Public contact point

Organisation

Fondazione GONO Plus

Contact name

Paolo Bossi

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications