Pilot Study of Sonidegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma

Phase 2

Terminated

Conditions: Carcinoma, Basal Cell
Recurrent Skin Cancer
Basal Cell Nevus Syndrome
Skin Neoplasms

Brief Summary: This pilot trial studies how well sonidegib and buparlisib work in treating patients with basal cell carcinoma that has spread to other places in the body. Sonidegib and buparlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description: PRIMARY OBJECTIVES:

Estimate the overall response rate (ORR) of sonidegib (erismodegib) in combination with buparlisib (hereby referred to as "LB therapy") for patients with locally advanced or metastatic basal cell carcinoma (BCC) in Smoothened inhibitor-naive patients (Cohort 1) and those whose disease is refractory or relapsed on Smoothened inhibitor monotherapy (Cohort 2).

NOTE: This study does not compare the treatment effect between these 2 dissimilar participant groups.

SECONDARY OBJECTIVES:

* Estimate the median duration of response, on or after LB therapy.

* Assess the safety and tolerability of LB therapy.

* Assess the histopathologic effect of LB therapy in tumor biopsies obtained at baseline and following 12 weeks of treatment.

* Assess the effect of LB therapy on gene expression including Hedgehog pathway and phosphatidylinositol 3-kinase (PI3K) pathways.

* Assess correlation between gene mutations in Smoothened, suppressor of fused homolog (Sufu), patched (PTCH), glioma-associated oncogene homolog (Gli)1, 2 and gene expression profiles and response to LB therapy.

OUTLINE:

Patients receive sonidegib orally (PO) once daily (QD) and buparlisib PO QD on days 1 to 28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
BCC Smoothened inhibitor-naive	Sonidegib	Participants with locally advanced or metastatic basal cell carcinoma (BCC) and naive to treatment with Smoothened inhibitors receive sonidegib and buparlisib in repeating 28-day cycles in the absence of disease progression or unacceptable toxicity.
BCC refractory or relapsed after Smoothened inhibitor	Sonidegib	Participants with locally advanced or metastatic basal cell carcinoma (BCC) that is refractory or relapsed after treatment with Smoothened inhibitors receive sonidegib and buparlisib in repeating 28-day cycles in the absence of disease progression or unacceptable toxicity.
BCC Smoothened inhibitor-naive	Buparlisib	Participants with locally advanced or metastatic basal cell carcinoma (BCC) and naive to treatment with Smoothened inhibitors receive sonidegib and buparlisib in repeating 28-day cycles in the absence of disease progression or unacceptable toxicity.
BCC refractory or relapsed after Smoothened inhibitor	Buparlisib	Participants with locally advanced or metastatic basal cell carcinoma (BCC) that is refractory or relapsed after treatment with Smoothened inhibitors receive sonidegib and buparlisib in repeating 28-day cycles in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Up to 2 years	Response was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria, and reported as overall response rate (ORR), comprised of the sum of complete response (CR) rate and partial response (PR) rate. * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR

Secondary Outcome Measures

Name	Time	Method
Median Duration of Response	up to 12 weeks	Response per the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria was monitored for duration of response (DOR) * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions * Stable disease (SD) = Small changes that do not meet any of the above criteria
Adverse Event Frequency	Up to 30 days post-treatment	Adverse events, graded according to the National Cancer Institute CTCAE version 3.0, are reported by treatment arm in total and by Grade 1 to 5.
Changes in Gene Expression Profiles of BCCs Including Hedgehog Pathway and PI3K Pathways	Baseline to 2 years	Immunostaining for the Gli-1; Gli-2; "Patched" (Ptch) ; "Suppressor of Fused" (SuFu); "Smoothened" (Smo)"; and phosphatidylinositol-3-kinase (PI3K) cellular biomarkers were to be contacted at baseline and after 12 weeks of treatment.
Gene Expression Profiles (Correlation of Particular Gene Expression Profiles and Response to LB Therapy Will be Assessed.)	up to 2 years post-treatment	The gene expression profiles for Gli-1; Gli-2; "Patched" (Ptch) ; "Suppressor of Fused" (SuFu); "Smoothened" (Smo)"; and phosphatidylinositol-3-kinase (PI3K) were to be correlated to the clinical response to therapeutic therapy.