Clinical Trial: Pembrolizumab in High-risk Ductal Carcinoma in Situ (DCIS)

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

Official Title: Testing the Ability of Pembrolizumab to Alter the Tumor Immune MicroEnvironment (TIME) of High Risk DCIS

Brief Summary: This is a pilot study to investigate the change in the immune microenvironment of high risk ductal carcinoma in situ (DCIS) after short term exposure to pembrolizumab.

Detailed Summary: This study will include 3 dose cohorts using a 3+3 cohort dose escalation design (see figure 1) followed by a 4th cohort at the maximum tolerated dose. Unless a dose limiting toxicity (DLT), defined any grade 3 or 4 toxicity, is observed requiring expansion of a cohort or a subject withdraws, 3 subjects will be enrolled into each cohort in the dose escalation phase. Subjects, upon diagnosis with high risk DCIS, will be offered 2 doses of pembrolizumab injected intralesionally (IL) 3 weeks apart (+/- 1 week) with surgery 3 weeks (+/- 2 weeks) after the 2nd dose. The subject will then undergo the surgical treatment as determined by the surgeon and the subject (partial mastectomy or mastectomy). The primary objective of this phase of the study will be safety and feasibility of intralesional injection of pembrolizumab. The maximum tolerated dose will be used in the expansion phase. The expansion cohort will have a target enrollment of 30 subjects randomized to either the control group or the treatment group. 10 subjects will be randomized to the control group and 20 subjects will be randomized to the treatment group. The control group will proceed to surgery alone following the diagnosis of high risk DCIS. The treatment group will receive 2 doses of intralesional pembrolizumab 3 weeks apart (+/- 1 week) prior to surgery. All subjects in the expansion cohort will also undergo a baseline MRI at diagnosis and undergo a 2nd MRI prior to surgery. Baseline and pre-surgical MRI images will be evaluated for changes in tumor volume.
Sponsor: Laura Esserman

Current Primary Outcome:

• Maximum tolerated dose (MTD) [ Time Frame: 18 months ]
  To determine the maximum tolerated dose (MTD), and recommended dose for subsequent expansion cohort, of intralesionally administered pembrolizumab in patients with ductal carcinoma in situ (DCIS) of the breast.
• Dose-limiting toxicities (DLTs) [ Time Frame: 18 months ]
  To define the dose-limiting toxicities (DLTs), tolerability, and feasibility of intralesional administration of pembrolizumab in patients with DCIS.
• Percentage of patients who demonstrate an increase (baseline vs. post intralesional injection) in intralesional CD8+ T cells (treated vs. untreated participants) as measured using multiplex immunofluorescence on FFPE tissue sections [ Time Frame: post intralesional injection ]
  To determine the response rate to intralesional pembrolizumab in patients with DCIS, as measured by an increase (baseline vs. post treatment) in intralesional CD8+ T cells, compared to untreated controls.

Original Primary Outcome:

• Maximum tolerated dose (MTD) [ Time Frame: 18 months ]
  To determine the maximum tolerated dose (MTD), and recommended dose for subsequent expansion cohort, of intralesionally administered pembrolizumab in patients with ductal carcinoma in situ (DCIS) of the breast.
• Dose-limiting toxicities (DLTs) [ Time Frame: 18 months ]
  To define the dose-limiting toxicities (DLTs), tolerability, and feasibility of intralesional administration of pembrolizumab in patients with DCIS.
• Percentage of patients who demonstrate an increase (baseline vs. post intralesional injection) in intralesional CD8+ T cells (treated vs. untreated participants) as measured using multiplex immunofluorescence on FFPE tissue sections [ Time Frame: baseline ]
  To determine the response rate to intralesional pembrolizumab in patients with DCIS, as measured by an increase (baseline vs. post treatment) in intralesional CD8+ T cells, compared to untreated controls.

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University of California, San Francisco

Dates:
Date Received: August 10, 2016
Date Started: August 2016
Date Completion: September 2018
Last Updated: August 18, 2016
Last Verified: August 2016