Sonibec

Basal Cell Carcinoma (BCC) is the most common cancer in white-skinned people with increasing incidence rates worldwide. In most patients, BCC can be treated with surgery, radiotherapy, and/or superficial field therapies; however, a minority of patients develop advanced BCC, for which treatment can be challenging and outcomes are poorer. BCC is characterized by molecular alterations in the Hedgehog pathway including inactivating mutations in PTCH1 in 85–90% and activating mutations in SMO in 10%. Sonidegib is a drug targeting Hedgehog patwhay approved by FDA and EMA for treatment of BCC. Clinical trials showed activity and efficacy of sonidegib at a dose of 200 mg daily (oral compounds). However, given the drug burden of toxicities, compliance to study treatment is usually low, in particular, patients that reached a complete response tend to interrupt the treatment, with a consequent risk of lower disease control. Thus, there is a need to make this treatment more tolerable and to improve compliance to sonidegib after obtaining complete response as the persistence on treatment could reflect on better disease control. If we consider data with similar compound, vismodegib (similar Hedgehog pathway inhibitor), for the patiens that achieved a complete response that interrupted the drug, 60% experienced a relapse of disease. Maintenance of complete response for patients represents a meaningful issue; this endpoint is often not achieved due to the difficulty for the patient to remain on treatment because of low compliance in continuous Hedgehog inhibitors assumption. In this regard, there are studies that tested intermittent vismodegib dosing schedules with the aim to improve compliance showing long-term efficacy and reduction of adverse events. SONIBEC study is a phase 2, single arm clinical trial in which patients in complete response with any inhibitor of Hedgehog pathway, will start receiving sonidegib 200 mg 14 days on and 14 days off on a 28 days cycle. In case the patients will experience with such a schedule any grade 2 or 3 toxicities (CTCAE 5.0) lasting for more than 28 days, despite treatment interruption, the patients will start receiving sonidegib 7 days on and 21 days off on 28 days cycle. In case of further unacceptable toxicities, treatment will be interrupted

Main selection criteria are:
– histological diagnosis of locally advanced BCC;
– patients with BCC already in treatment with any inhibitor of Hedgehog pathway;
– patients having shown a complete response to any inhibitor of Hedgehog pathway within 3 months prior to the screening (effort should be made to obtain a histologic confirmation of complete response in the site where disease was present; alternatively complete response must be confirmed by 2 consecutive radiologic exams and by visual and dermoscopic evaluations)
– PS ECOG 0-2
– Adequate bone marrow and organ functionality.

Primary objective of the study is to evaluate the compliance to a tailored regimen of sonidegib in patients who have previously obtained a complete response assuming any inhibitor of Hedgehog pathway in terms of proportion of patients maintaining the tailored treatment with sonidegib 12 months after study enrollment. Secondary objectives are to evaluate the compliance of study treatment, to evaluate the safety of study treatment, to assess patients quality of life (by using ESAS scale), and to assess the use of concomitant medication. The exploratory objective is to evaluate changes in the molecular pattern of BCC after achieving complete response and in the microenvironment in naive and pre treated BCC.