Trial Combining Pembrolizumab and Cesium 131 Brachytherapy With Salvage Surgery in HNSCC

Phase 1b/II Trial Combining PD1 Inhibition (Pembrolizumab) and Cesium 131 Brachytherapy With Salvage Surgery to Enhance Immunogenicity and Improve Local Control in Head and Neck Cancer

To Study Perioperative PD-1 Inhibitor and Cesium-131 Interstitial Brachytherapy in patients with locally recurrent HNSCC eligible for salvage surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: HNSCC
• Intervention / Treatment: Device: Cesium-131; Drug: Pembrolizumab

Detailed Description

This study is a non-randomized, single-arm, multi-institutional phase 1b/II study including patients with locally recurrent head and neck cancer eligible for resection. Patients who are identified to be eligible for surgical resection will be screened and consented to receive one 200mg IV dose of pembrolizumab followed by salvage surgery. At the time of surgery, they will have Cesium131 seeds implanted. Two to six weeks after surgery, subjects will be started on 200 mg IV of pembrolizumab to be continued every 3 weeks for 6 months. The phase 1b part will enroll 3 patients for a safety run-in, followed by the phase 2 part if no DLTs are seen in these 3 patients. Phase 2 will be used to estimate the 2-year DFS in comparison to a benchmark selected based on a historical control. For correlative studies, archived tissue and surgical specimen will be evaluated by H&E and IHC for immune phenotype. Blood samples will also be collected as shown in schema above for correlative studies (blood will be collected for correlatives and biomarkers before and after the first of pembrolizumab, before starting adjuvant pembrolizumab and at completion of 6 month course of adjuvant pembrolizumab). Patients will be followed approximately every 3 weeks during treatment for the first 6 months, then monthly for 3 months following treatment and then every 3 months thereafter for 24 months for disease free survival (DFS) and overall survival (OS).

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: UCCC Clinical Trials Office; Phone Number: 513-584-7698; Email: cancer@uchealth.com

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19144
      • Thomas Jefferson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• locally recurrent HNSCC and be eligible for salvage surgery
• If patient received radiation therapy in the past, they should have recovered from the acute toxicity to <grade 1
• tumor needs to be deemed resectable

Exclusion Criteria:

• Exposed carotid artery preoperatively requiring sacrifice or bypass intra-operatively
• Patients with active pharyngo-cutaneous
• Patients with more than one site of distant metastatic disease
• Prior immune-based anticancer therapy within last six months

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 & Cesium-131; 200 mg Pembrolizumab (Day -14 pre-surgery; Every 3 weeks after surgery) + Cesium-131 Seeds to deliver 60-70Gy of radiation (Single dose at the time of salvage surgery)

Device: Cesium-131; Cs-131 brachytherapy seed is a low-energy-gamma isotope that is contained in a titanium capsule. Dosing will be determined by a radiation oncologist study team member based on CT scan and intraoperative findings. The number of seeds and spacing will be outlined preoperatively based on the proposed square area of exposure in the resection bed. The plan is to deliver a total of 60-70Gy of radiation to the site.; Other Names: Cs-131; Drug: Pembrolizumab; Pembrolizumab 200 mg will be administered as a 30-minute IV infusion every 3 weeks. The drug will be infused through a peripheral line or an indwelling catheter. The first dose will be given 2 weeks prior to surgery. Post-surgery, pembrolizumab will be started between 2 and 6 weeks and will continue every 3 weeks for a duration of 6 months. Study Drug may be administered up to 3 days before or after the scheduled Day 1 of each cycle due to administrative reasons. The Investigator's Brochure contains specific instructions for the preparation of the standard of care pembrolizumab infusion fluid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Safety measured by dose limiting toxicities (DLTs).	Phase Ib: To determine the safety of the combination of pembrolizumab and Cesium-131 in recurrent HNSCC patients undergoing salvage surgical resection. A 3+3 safety run in will be conducted for the phase 1b part of the protocol. Safety monitoring will begin at the time of enrollment on the study and will continue for at least 4 weeks after completion of the last treatment dose on study.	2 years
Disease-free survival	Phase II: To estimate the disease-free survival (DFS) rate for the combination of pembrolizumab and Cesium 131 in recurrent HNSCC patients undergoing salvage surgical resection	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	To estimate the Overall Survival (OS) Rate	4 years
Loco-regional control rate	To estimate the Loco-regional control rate (LCR)	4 years
Adverse events	To estimate the frequency and severity of adverse events (AE)	4 years

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: IsoRay Medical, Inc.
• Investigators: Principal Investigator: Chad Zender, MD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2021
• Primary Completion (Estimated): February 4, 2025
• Study Completion (Estimated): February 4, 2025

Study Registration Dates

• First Submitted: April 5, 2020
• First Submitted That Met QC Criteria: April 7, 2020
• First Posted (Actual): April 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

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; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: UCCC-HN-20-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No