A Phase II, Open-Label, Safety, Efficacy and Pharmacodynamic Study of oral sonidegib in patients with Basal Cell Carcinoma (BCC) and prior exposure to Hedgehog Pathway inhibitors
- Conditions
- Basal Cell CarcinomaTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-004113-13-BE
- Lead Sponsor
- GZA vzw, GZA Ziekenhuizen, Sint-Augustinus
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
?Understand and voluntarily sign an Institutional Review Board/Independent Ethics Committee-approved informed consent form prior to any study-specific evaluation
?Be 18 years of age at the time the informed consent form is signed
?Have an Eastern Cooperative Oncology Group performance status of 0 to 1
?Have life expectancy of at least 3 months
?Have adequate organ function confirmed by the following laboratory values obtained within 14 days of the first dose of LDE
Bone marrow function
•ANC > 1,5 x 109/L
•Platelets > 100 x 109/L
•Hemoglobin > 9 g/dL
Hepatic function
•Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN); if liver metastases then < 5 x ULN, Bilirubin < 1,5 x ULN
Renal function
•Serum creatinine < 1,5 x ULN
?Have a normal clinical cardiac evaluation
?Have a histologically or cytologically proven BCC
?Have evidence of measurable disease as defined by RECIST Version 1.1 or have lesions that can be biopsied and can be photographically assessed
?Must have been pretreated with either vismodegib or sonidegib
?Must have progressed or became intolerant for further treatment with vismodegib or have progressed after having experienced clinical benefit of treatment with sonidegib
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 28
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28
?History of prior malignancy except:
Curatively treated in-situ cervical cancer
Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
?Untreated or symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least 4 weeks
?Impaired cardiac function or clinically significant cardiac disease, including any of the following:
Unstable angina pectoris
Acute myocardial infarction
?Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or history of chronic hepatitis B or C
?Treatment with chemotherapy, radiation, hormones (except corticosteroids and megestrol acetate), antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitor, or experimental drugs 14 days prior to first scheduled dose of sonidegib and/or ongoing adverse effects from such treatment > NCI CTCAE Grade 1
?Treament with HPI needs to be discontinued for at least 2 weeks
?Females who are pregnant or breastfeeding
?For fertile patients (male and female), refusal to use effective contraception during the period of the trial and for 6 months after the last dose of sonidegib
?Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g. substance abuse, psychiatric disturbance, or uncontrolled intercurrent illness including active infection, arterial thrombosis, and symptomatic pulmonary embolism)
?Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results, and, in the opinion of the investigator, would make the patient inappropriate for entry into the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: ?To evaluate overall response rate and the duration of response (ORR) in patients with locally advanced and/or inoperable BCC after prior treatment with both vismodegib and sonidegib, using 800 mg sonidegib daily;Secondary Objective: ?To evaluate the pathological response in patients with non-sonidegib pre-treated BCC and after treatment with sonidegib<br>?To evaluate the safety profile of continuous daily dosing of sonidegib in patients with BCC;Primary end point(s): ?ORR per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in patients with LA-BCC and metastatic BCC<br>?ORR per photography in patients with multiple inoperable BCCs, not measurable by standard RECIST 1.1<br>?Duration of response and clinical benefit will be determined from the start of treatment with sonidegib until progression;Timepoint(s) of evaluation of this end point: First evaluation at Week 9, thereafter every 8 weeks and at End of Treatment.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): ?To determine the degree of change in cellularity, Ki67 index and apoptotic index, comparing pre-treatment biopsies with a tumour sample obtained after 6 to 8 weeks on sonidegib<br>?To determine the activity of Hedgehog signaling pathway based on Gli1 mRNA expression prior to and after 6 to 8 weeks on sonidegib<br>?The incidence of Grade 3 or 4 adverse events (AEs) and clinical laboratory abnormalities defined as dose-limiting toxicities (DLTs);Timepoint(s) of evaluation of this end point: Tumour biopsy at Week 9 and Week 17 and at End of Treatment, Laboratory evaluation at Week 5 and Week 9, thereafter every 8 weeks and at End of Treatment, Evaluation of Adverse Events from Informed Consent until at least 30 days following the last dose of the study treatment.