Phase II Trial of Adjuvant Cisplatin and Radiation With Pembrolizumab in Resected Head and Neck Squamous Cell Carcinoma

Phase II Investigation of Adjuvant Combined Cisplatin and Radiation With Pembrolizumab in Resected Head and Neck Squamous Cell Carcinoma

The purpose of this research study is to test the safety and the benefit of adding pembrolizumab (a therapy that activates the immune system to fight cancer) to standard of care treatment for head and neck cancer. The standard of care treatment will include surgery followed by radiation for 6 weeks. Some patients may also receive cisplatin as standard of care once a week for 6 weeks if the cancer is found to be "high risk". High risk includes cancer that was not completely removed (positive margins) or cancer that has invaded through the outer lining of your lymph nodes.

Study Overview

• Status: Active, not recruiting
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Procedure: Surgery; Radiation: Radiation Therapy; Drug: Cisplatin

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville - James Graham Brown Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients eligible for resection with one or more of the following

  1. Any T stage with ≥ N2 disease;
  2. T4 disease, any N stage;
  3. T3 Oral Cavity, any N stage; or
  4. Clinical evidence of extra-capsular extension on scans.
• Must be willing to undergo definitive resection with neck dissection.
• Performance status 0 or 1 on Eastern Cooperative Oncology Group Performance Scale.
• Adequate labs
• Appropriate staging imaging.

Exclusion Criteria:

• Diagnosis of immunodeficiency or receiving systemic steroid therapy or immunosuppressive therapy within 7 days prior to planned first dose of trial treatment.
• Nasopharyngeal or sinonasal carcinoma
• Confirmed metastatic disease
• Human Papillomavirus (HPV)+ disease of the oropharynx
• Known history of active tuberculosis (TB), autoimmune disease, pneumonitis, infection, HIV, Hepatitis B, or Hepatitis C

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab; Pembrolizumab in combination with standard of care surgery followed by radiation therapy with or without cisplatin	Drug: Pembrolizumab; Pembrolizumab administered one week prior to surgery and then every three weeks in the adjuvant setting for a total of 7 doses.; Other Names: Keytruda; Procedure: Surgery; gross total surgical resection; Radiation: Radiation Therapy; 60-66 Gy over 6 weeks; Drug: Cisplatin; Weekly during radiation therapy for 6 doses only for patients with high risk pathological features

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Related Adverse Effects	Number of participants with treatment related adverse effects as assessed using CTCAE v4.0 of pembrolizumab when combined with radiation alone and chemoradiation. Compared as percentage of grade 3 and 4 adverse events with historical control percentages.	All adverse events were recorded from the time the consent form is signed through 30 days following cessation of treatment. Any AE related to study drug after 30 days post treatment, subjects were followed until resolution.
Disease Free Survival in Resected High Risk Patients Treated With Adjuvant Pembrolizumab and Chemoradiation	• High risk is defined as those with biopsies that have the following features: extracapsular spread or those with positive surgical margins.	1 year
Disease Free Survival in Resected Intermediate Risk Patients Treated With Adjuvant Pembrolizumab and Radiation	• Intermediate risk is defined as those with biopsies that do not have the following features: extracapsular spread or those with positive surgical margins.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Immune Response to Pembrolizumab as Defined by PD-L1 CPS in the Baseline Tumor Tissue	Change in distribution of the tumor immune microenvironment after Pembrolizumab administration in tumor biopsy tissue using markers of T cells and T cell activation using PD-L1 CPS. PD-L1 CPS is defined as the PD-L1 combined positive score. PD-L1 CPS is defined as Combined positivity score (CPS) was calculated by summing the numbers of PD-L1-positive tumor cells and immune cells and dividing by the total number of viable tumor cells. Additionally, PD-L1 is a protein that helps the body immune system remain in control. The denominator in this case is 72 subjects that were evaluable. Evaluable means the subject had a pre-surgery pembrolizumab and a biopsy taken. The numerators are explained below.	1 week between receiving a pre-surgery dose of pembrolizumab and surgery when the biopsy was taken
Overall Survival in Resected Intermediate Risk Patients Treated With Adjuvant Pembrolizumab and Radiation	• Intermediate risk is defined as those with biopsies that do not have the following features: extracapsular spread or those with positive surgical margins	1 year
Overall Survival in Resected High Risk Patients Treated With Adjuvant Pembrolizumab and Chemoradiation	• High risk is defined as those with biopsies that have the following features: extracapsular spread or those with positive surgical margins.	1 year

Collaborators and Investigators

• Sponsor: Trisha Wise-Draper
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): April 16, 2021
• Study Completion (Anticipated): November 2, 2025

Study Registration Dates

• First Submitted: December 21, 2015
• First Submitted That Met QC Criteria: December 23, 2015
• First Posted (Estimate): December 29, 2015

Study Record Updates

• Last Update Posted (Estimate): May 4, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: UCCI-HN-15-01