Clinical trial NCT04340258: Trial Combining Pembrolizumab and Cesium 131 Brachytherapy With Salvage Surgery in HNSCC
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: HNSCC
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: IsoRay Medical, Inc.
First posted: 2020-04-09
Enrollment: 50
Sex: ALL
Minimum age (years): 19
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Non-randomized, single-arm
Primary purpose: TREATMENT

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

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).

Eligibility 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

Primary outcomes:
measure: Overall Safety measured by dose limiting toxicities (DLTs).
timeFrame: 2 years
measure: Disease-free survival
timeFrame: 2 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 4 years
measure: Loco-regional control rate
timeFrame: 4 years
measure: Adverse events
timeFrame: 4 years
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson
state: Pennsylvania
Study officials:
affiliation: University of Cincinnati
name: Chad Zender, MD
role: PRINCIPAL_INVESTIGATOR
References: