Clinical Trial: Pembrolizumab With or Without Vismodegib in Treating Metastatic or Unresectable Basal Cell Skin Cancer

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase Ib Open Label Study of Pembrolizumab for Unresectable or Metastatic Basal Cell Carcinoma

Brief Summary: This phase II trial studies how well pembrolizumab with or without vismodegib works in treating patients with skin basal cell cancer that has spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab, blocks tumor growth in different ways by targeting certain cells. Vismodegib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether pembrolizumab is more effective alone or together with vismodegib in treating skin basal cell cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the overall response rate (ORR) of unresectable or metastatic basal cell carcinoma (BCC) patients to pembrolizumab monotherapy after disease progression on smoothened inhibitor monotherapy.

II. Determine the overall response rate (ORR) of unresectable or metastatic BCC patients to pembrolizumab plus vismodegib after partial response or stable disease on smoothened inhibitor monotherapy.

SECONDARY OBJECTIVES:

I. Determine the nature and severity of adverse events while on pembrolizumab for BCCs.

II. Determine the nature and severity of adverse events while on pembrolizumab plus vismodegib for BCCs.

III. Determine whether levels of lymphocytic infiltration and programmed cell death ligand (PDL)1 are increased after treatment with pembrolizumab, as well as additional search for immunologic biomarkers for response such as cluster of differentiation (CD)8 density in patients with unresectable or metastatic BCC.

IV. Determine whether levels of lymphocytic infiltration and PDL1 are increased after treatment with pembrolizumab plus vismodegib, as well as additional search for immunologic biomarkers for response such as CD8 in patients with unresectable or metastatic BCC.

OUTLINE: Patients are assigned to 1 of 2 treatment arms.

ARM I: Patients experiencing disease progression during previous treatment with vismodegib receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses every 21 days for 24 months in the absence of disease progression
Sponsor: Anne Chang

Current Primary Outcome:

• ORR of unresectable or metastatic BCC patients who have progressive disease on smoothened inhibitor monotherapy to pembrolizumab assessed using RECIST version 1.1 [ Time Frame: Up to 2 years ]
  Overall response rate of the two arms will be calculated and compared.
• ORR of unresectable or metastatic BCC patients who have stable disease or partial response to pembrolizumab plus vismodegib assessed using RECIST version 1.1 [ Time Frame: Up to 2 years ]
  Overall response rate of the two arms will be calculated and compared.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Incidence of adverse event in patients while on pembrolizumab for BCCs graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [ Time Frame: Up to 90 days after completion of study treatment ]
  The nature and severity of adverse events will be tallied for the events of interest and compared between arms.
• Incidence of adverse events in patients while on pembrolizumab plus vismodegib for BCCs graded according to CTCAE version 4.03 [ Time Frame: Up to 90 days after completion of study treatment ]
  The nature and severity of adverse events will be tallied for the events of interest and compared between arms.
• Levels of lymphocytic infiltration after treatment with pembrolizumab [ Time Frame: Up to 2 years ]
  The levels of lymphocytic infiltration after treatment with pembrolizumab in patients with unresectable or metastatic BCC will be tallied and compared between arms.
• Levels of PDL1 after treatment with pembrolizumab [ Time Frame: Up to 2 years ]
  The levels of PDL1 after treatment with pembrolizumab in patients with unresectable or metastatic BCC will be tallied and compared between arms.
• Levels of lymphocytic infiltration after treatment with pembrolizumab plus vismodegib [ Time Frame: Up to 2 years ]
  The levels of lymphocytic infiltration after treatment with pembrolizumab plus vismodegib in patients with unresectable or metastatic BCC will be tallied and compared between arms.
• Levels of PDL1 after treatment with pembrolizumab plus vismodegib [ Time Frame: Up to 2 years ]
  The levels of PDL1 after treatment with pembrolizumab plus vismodegib in patients with unresectable or metastatic BCC will be tallied and compared between arms.
• Overall survival (OS) [ Time Frame: Up to 2 years ]
  To calculate OS, the Kaplan-Meier analysis will be performed.
• Progression free survival (PFS) [ Time Frame: Up to 2 years ]
  To calculate PFS, the Kaplan-Meier analysis will be performed.

Original Secondary Outcome: Same as current

Information By: Stanford University

Dates:
Date Received: February 12, 2016
Date Started: February 2016
Date Completion:
Last Updated: February 1, 2017
Last Verified: February 2017