Tailored schedule of sonidegib for advanced skin cancer treatment

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

This study is testing a new way to give sonidegib to adults with advanced skin cancer to see if a tailored schedule can reduce side effects while still being effective.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 21 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Gruppo Oncologico del Nord-Ovest (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Brescia)
• Trial ID: NCT04806646 on ClinicalTrials.gov

What this trial studies

This clinical trial focuses on adult patients with locally advanced basal cell carcinoma (BCC) who have achieved a complete response to Hedgehog inhibitors. Participants will receive sonidegib on a tailored schedule that alternates between periods of drug administration and suspension, aiming to minimize side effects while maintaining treatment efficacy. The study includes two treatment schedules: one with 14 days on and 14 days off, and another with 7 days on and 21 days off, with adjustments made based on patient tolerance and side effects. The goal is to evaluate the effectiveness and safety of this tailored approach in managing BCC.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed locally advanced BCC who have shown a complete response to sonidegib.

Not a fit: Patients with BCC that has not responded to Hedgehog inhibitors or those who are not suitable for the tailored treatment schedules may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective and tolerable treatment option for patients with advanced BCC who cannot undergo surgery.

How similar studies have performed: While tailored treatment schedules are a novel approach in this context, similar studies have shown promise in optimizing drug administration for other conditions.

Eligibility criteria

Inclusion Criteria:

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 sonidegib 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 sonidegib 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. Women of child-bearing potential must use two methods of acceptable contraception including one highly effective method and a barrier method, as directed by their physician, during treatment and for at least 20 months after completion of study treatment. 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, combined oral contraception, or intra-uterine devices). Check Appendix B for details.
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:

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.

Where this trial is running

Brescia

• Asst Degli Spedali Civili Di Brescia — Brescia, Italy (Recruiting)

Study contacts

• Principal investigator: Paolo Bossi, MD — Gono - ASST Spedali Civili Brescia
• Study coordinator: Mariarita Arenella

Conditions Locally Advanced Basal Cell Carcinoma