Phase I/ II Trial Combining PD-1 Inhibition and Neoadjuvant Proton or Photon Radiation Therapy in Recurrent Head and Neck Squamous Cell Carcinoma
- Conditions
- Head and Neck CancerRecurrent Head and Neck Squamous Cell Carcinoma
- Interventions
- Radiation: Proton therapy
- Registration Number
- NCT07213934
- Lead Sponsor
- University of Cincinnati
- Brief Summary
The purpose of the Phase I study is to see if it is safe to use X-ray photon radiation (XRT) and proton radiation (PT) before surgery in patients with recurrent head and neck squamous cell carcinoma (rHNSCC).
The purpose of the Phase II study is to see if using XRT or PT before immunotherapy (pembrolizumab) prior to surgery benefits patients with recurrent head and neck squamous cell carcinoma (rHNSCC).
- Detailed Description
In phase I, cohorts of 3 to 6 patients will be treated with 3 fractions of RT prior to surgery. A de-escalation cohort is planned if toxicity is exceeded in Cohort 1. The types of RT (XRT and PT) will be tested sequentially. The first cohort will include XRT followed by salvage surgery and adjuvant immunotherapy. The RP2D or dose found to be safe will be decided for XRT first. The RP2D for XRT will then be the starting dose cohort for PT to ensure the dose remains safe. The highest dose found to be safe for both types of RT will be used for Phase II. The dose escalation criteria must be met at each dose level including up to 28 days post-surgical resection in order to enroll and treat pts for phase II or de-escalate to the indicated dose level.
Phase II is a two arm window of opportunity multi-center study investigating XRT or PT with PD-1 inhibition in recurrent HNSCC. The study will be conducted in two stages with 2 independent experimental arms based on a Simons 2 Stage Design. PT followed by PD-1 inhibition (Arm 1) or XRT followed by PD-1 inhibition (Arm 2) will be independently compared to a historical control group with the primary endpoint of major pathological response (MPR) and a goal of 35% of patients achieving MPR compared to a baseline of 10% with PD-1 alone. Forty total patients with recurrent HNSCC will be screened and randomized to avoid selection bias to either PT or XRT. Based on a Simon Stage 2 Design, nine patients are required for stage I. Stage II will proceed after determination of Stage I MPR.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard Radiation Therapy Pembrolizumab XRT followed by PD-1 inhibition Photon Therapy Proton therapy PT followed by PD-1 inhibition Photon Therapy Pembrolizumab PT followed by PD-1 inhibition
- Primary Outcome Measures
Name Time Method Dose Limiting Toxicity (DLT) Evaluation defined as the number of subjects experiencing a major, non-grade 5 adverse event as defined by CTCAE v6 or a grade 5 adverse event as defined by CTCAE 6. From the initiation of study treatment to a minimum of 30 days following the end of active study treatment. To determine DLTs during Phase I to determine the recommended Phase 2 dose. A DLT is defined as experiencing ≥ Gr 4 AEs prior to surgery, a delay in surgery past 5 wks from RT, or ≥ Gr 4 surgical complications or Grade 5 adverse events are defined as deaths occurring during the study period, regardless of attribution, as assessed using CTCAE v6.0 criteria.
Major Pathologic Response (MPR) defined as less than 10% viable tumor on resected tumor specimen. Surgery - Week 4 To determine the major pathological response (MPR) in patients undergoing neoadjuvant X-ray photon radiation (XRT) or proton radiation (PT) with pembrolizumab followed by surgical salvage compared to a historical control group undergoing salvage surgery with PD-1 alone.
- Secondary Outcome Measures
Name Time Method Disease Free Survival as measured from time of surgery until either disease recurrence or death from any cause. Surgery - Week 4 through 5 years To determine the disease-free survival (DFS) in patients undergoing neoadjuvant XRT or PT followed by surgical salvage compared to a historical control group undergoing salvage surgery alone. DFS is defined as the duration from time of surgery until either disease progression, recurrence or death due to any cause.
Safety using CTCAE v6.0 and toxicity evaluation. 5 years To determine the safety of neoadjuvant pembrolizumab combined with XRT or PT prior to salvage surgery.
Trial Locations
- Locations (1)
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati Medical Center🇺🇸Cincinnati, Ohio, United States