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

• ClinicalTrials.gov Identifier: NCT04340258
• Recruitment Status: Recruiting
• First Posted: April 9, 2020
• Last Update Posted: March 4, 2021
• Sponsor: University of Cincinnati
• Collaborator: IsoRay Medical, Inc.
• Information provided by (Responsible Party): Shuchi Gulati, University of Cincinnati

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
HNSCC	Device: Cesium-131; Drug: Pembrolizumab	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Non-randomized, single-arm
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 4, 2021
• Estimated Primary Completion Date: February 4, 2023
• Estimated Study Completion Date: February 4, 2025

Arms and Interventions

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Overall Safety measured by dose limiting toxicities (DLTs). [ Time Frame: 2 years ]
   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. Disease-free survival [ Time Frame: 2 years ]
   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

Secondary Outcome Measures :

1. Overall Survival [ Time Frame: 4 years ]
   To estimate the Overall Survival (OS) Rate
2. Loco-regional control rate [ Time Frame: 4 years ]
   To estimate the Loco-regional control rate (LCR)
3. Adverse events [ Time Frame: 4 years ]
   To estimate the frequency and severity of adverse events (AE)

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: UCCC Clinical Trials Office; 513-584-7698; cancer@uchealth.com

Locations

United States, Ohio

University of Cincinnati Medical Center; Recruiting

Cincinnati, Ohio, United States, 45219

Contact: UCCC CTO 513-584-7698 cancer@uchealth.com

Principal Investigator: Shuchi Gulati, MD

Case Western Reserve; Not yet recruiting

Cleveland, Ohio, United States, 44106

United States, Pennsylvania

Thomas Jefferson; Not yet recruiting

Philadelphia, Pennsylvania, United States, 19144

Sponsors and Collaborators

University of Cincinnati

IsoRay Medical, Inc.

Investigators

• Principal Investigator: Shuchi Gulati, MD; University of Cincinnati

More Information

• Responsible Party: Shuchi Gulati, Principal Investigator, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT04340258
• Other Study ID Numbers: UCCC-HN-20-01
• First Posted: April 9, 2020
• Last Update Posted: March 4, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents