Clinical Trial: Sonidegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: An Open-Label Pilot Study to Evaluate the Efficacy and Safety of a Combination Treatment of Sonidegib (LDE225) and Buparlisib (BKM120) For the Treatment of Advanced Basal Cell Carcinomas

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 Summary:

PRIMARY OBJECTIVES:

I. To 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).

SECONDARY OBJECTIVES:

I. To estimate the median duration of response, on or after LB therapy. II. To assess the safety and tolerability of LB therapy. III. To assess the histopathologic effect of LB therapy in tumor biopsies obtained at baseline and following 12 weeks of treatment.

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

V. To 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 1-28. 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.


Sponsor: Anne Chang

Current Primary Outcome: ORR by Response Evaluation Criteria In Solid Tumors 1.1 criteria [ Time Frame: Up to 2 years ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Median duration of response [ Time Frame: After 12 weeks of treatment ]
  • Frequency of adverse events, graded according to the National Cancer Institute CTCAE version 3.0 [ Time Frame: Up to 30 days post-treatment ]
  • Changes in gene expression profiles of BCCs including Hedgehog pathway and PI3K pathways [ Time Frame: Baseline to 2 years ]
  • Gene expression profiles (Correlation of particular gene expression profiles and response to LB therapy will be assessed.) [ Time Frame: Up to 2 years ]
    Correlation of particular gene expression profiles and response to LB therapy will be assessed.


Original Secondary Outcome: Same as current

Information By: Stanford University

Dates:
Date Received: November 25, 2014
Date Started: February 2015
Date Completion: June 2017
Last Updated: April 24, 2017
Last Verified: April 2017