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

• ClinicalTrials.gov Identifier: NCT02641093
• Recruitment Status: Active, not recruiting
• First Posted: December 29, 2015
• Results First Posted: May 6, 2023
• Last Update Posted: May 6, 2023
• Sponsor: Trisha Wise-Draper
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Trisha Wise-Draper, University of Cincinnati

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Head and Neck Cancer	Drug: Pembrolizumab; Procedure: Surgery; Radiation: Radiation Therapy; Drug: Cisplatin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 96 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Investigation of Adjuvant Combined Cisplatin and Radiation With Pembrolizumab in Resected Head and Neck Squamous Cell Carcinoma
• Actual Study Start Date: January 2016
• Actual Primary Completion Date: April 16, 2021
• Estimated Study Completion Date: November 2, 2025

Arms and Interventions

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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment Related Adverse Effects [ Time Frame: 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. ]
   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.
2. Disease Free Survival in Resected High Risk Patients Treated With Adjuvant Pembrolizumab and Chemoradiation [ Time Frame: 1 year ]
   • High risk is defined as those with biopsies that have the following features: extracapsular spread or those with positive surgical margins.
3. Disease Free Survival in Resected Intermediate Risk Patients Treated With Adjuvant Pembrolizumab and Radiation [ Time Frame: 1 year ]
   • Intermediate risk is defined as those with biopsies that do not have the following features: extracapsular spread or those with positive surgical margins.

Secondary Outcome Measures :

1. Tumor Immune Response to Pembrolizumab as Defined by PD-L1 CPS in the Baseline Tumor Tissue [ Time Frame: 1 week between receiving a pre-surgery dose of pembrolizumab and surgery when the biopsy was taken ]

   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.

2. Overall Survival in Resected Intermediate Risk Patients Treated With Adjuvant Pembrolizumab and Radiation [ Time Frame: 1 year ]
   • Intermediate risk is defined as those with biopsies that do not have the following features: extracapsular spread or those with positive surgical margins
3. Overall Survival in Resected High Risk Patients Treated With Adjuvant Pembrolizumab and Chemoradiation [ Time Frame: 1 year ]
   • High risk is defined as those with biopsies that have the following features: extracapsular spread or those with positive surgical margins.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Kentucky

University of Louisville - James Graham Brown Cancer Center

Louisville, Kentucky, United States, 40202

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, Ohio

University of Cincinnati Medical Center

Cincinnati, Ohio, United States, 45219

Ohio State University

Columbus, Ohio, United States, 43210

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Trisha Wise-Draper

Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Trisha Wise-Draper, MD, PhD; University of Cincinnati

  Study Documents (Full-Text)

Documents provided by Trisha Wise-Draper, University of Cincinnati:

Study Protocol and Statistical Analysis Plan  [PDF] March 18, 2021

More Information

• Responsible Party: Trisha Wise-Draper, Principal Investigator, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT02641093
• Other Study ID Numbers: UCCI-HN-15-01
• First Posted: December 29, 2015
• Results First Posted: May 6, 2023
• Last Update Posted: May 6, 2023
• Last Verified: April 2023

Additional relevant MeSH terms:

Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Neoplasms by Site; Pembrolizumab; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action