The goal of this clinical trial is to evaluate if adding chemotherapy and immunotherapy as induction treatment prior to definitive chemoradiotherapy could improve the outcomes of locally advanced HPV-negative head and neck squamous cell that are not amenable to surgery. The study aims to answer: 1. Does this treatment improve the survival outcomes of participants? 2. How do the tumors of participants response to the treatment? 3. How is the safety of this treatment? Researchers will compare this treatment (induction chemoimmunotherapy, followed by concurrent chemoradiotherapy, and then immunotherapy as maintenance therapy) to concurrent chemoradiotherapy to see whether it provides additional clinical benefits.
This multicenter, prospective, open-label, phase II randomized controlled clinical trial plans to enroll 104 treatment naïve participants with locally advanced (III-IVB by UICC/AJCC 8th), unresectable or inoperable HPV-negative head and neck squamous cell carcinoma (HNSCC). Patients will be stratified by primary tumor site (oropharynx vs. non-oropharynx) and randomly assigned (1:1) to one of two treatment arms: (1) Arm A (Experimental): Induction phase, three cycles of tislelizumab plus paclitaxel and cisplatin; Concurrent chemoradiotherapy (CCRT) phase, definitive radiotherapy concurrent with two cycles of cisplatin; Adjuvant phase, 13 cycles of tislelizumab. (2) Arm B (Comparator): CCRT, definitive radiotherapy concurrent with two cycles of cisplatin. The primary hypothesis is that the addition of induction chemoimmunotherapy and adjuvant immunotherapy improves event-free survival compared to chemoradiotherapy alone.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
104
* As induction immunotherapy, 200 mg administered IV infusion on Day 1 of each 21-day cycle, for 3 cycles. * As adjuvant immunotherapy, 200 mg administered IV infusion on Day 1 of each 21-day cycle, for 13 cycles.
\- As induction chemotherapy, 175 mg/m2 administered IV infusion on Day 2 of each 21-day cycle, for 3 cycles.
\- As induction chemotherapy, 75 mg/m2 administered IV infusion on Day 2-4 of each 21-day cycle, for three cycles.
\- Definitive IMRT: 70Gy given in 35 fractions over 7 weeks
\- As concurrent chemotherapy, 80 mg/m2 administered IV infusion on Day 1-3 of each 21-day cycle, for two cycles.
Fudan Universtiy Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
Event-free Survival (EFS)
Defined as the time to the earliest occurrence of progressive disease that precluded chemoradiotherapy or prevented completion of chemoradiotherapy, disease recurrence, or death from any cause.
Time frame: 2 year
Overall Survival (OS)
Defined as the time from randomization to death due to any cause.
Time frame: 2 year
Locoregional Recurrence-Free Survival (LRFS)
Defined as the time from randomization to the first documented event of local or regional recurrence.
Time frame: 2 year
Distant Metastasis-free survival (DMFS)
Defined as the time from randomization to the first documented event of distant metastasis.
Time frame: 2 year
Objective Response Rate (ORR)
Defined as the proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST). ORR will be evaluated after induction treatment, CCRT, and adjuvant immunotherapy, respectively.
Time frame: Through study completion, an average of 1 year
Incidence of Adverse Events
All adverse events will be documented, including treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs), in the form of all-grade AEs and grade 3-4 AEs. AEs will be evaluated by investigators according to the Common Terminology Criteria for Adverse Events, version 5.0.
Time frame: 2 year
Quality of Life (QoL) (EORTC QLQ-H&N35)
Changes in QoL of participants from baseline to up to 6 months after the completion of adjuvant immunotherapy. QoL will be evaluated with the questionnaires of the head-and-neck-specific module (H\&N35) of the Quality of Life Questionnaire-Core 30 module (QLQ-C30).
Time frame: Baseline and up to 6 months
Quality of life (Qol) (FACT-HN)
Changes in QoL of participants from baseline to up to 6 months after the completion of adjuvant immunotherapy. QoL will be evaluated with the questionnaires of the general and head-and-neck-specific (HN) module of the evaluation tool developed by the Functional Assessment of Cancer Therapy (FACT).
Time frame: Baseline and up to 6 months
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