Trial Combining Pembrolizumab and Cesium 131 Brachytherapy With Salvage Surgery in HNSCC
- Registration Number
- NCT04340258
- Lead Sponsor
- University of Cincinnati
- 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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 50
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Pembrolizumab & Cesium-131 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) Pembrolizumab & Cesium-131 Pembrolizumab 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)
- Primary Outcome Measures
Name Time Method Disease-free survival 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
Overall Safety measured by dose limiting toxicities (DLTs). 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.
- Secondary Outcome Measures
Name Time Method Overall Survival 4 years To estimate the Overall Survival (OS) Rate
Loco-regional control rate 4 years To estimate the Loco-regional control rate (LCR)
Adverse events 4 years To estimate the frequency and severity of adverse events (AE)
Trial Locations
- Locations (2)
Thomas Jefferson
🇺🇸Philadelphia, Pennsylvania, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States