Locally Advanced Head and Neck Squamous Cell Carcinoma
Conditions
Brief summary
Most patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed with locally advanced disease. While cisplatin-based chemoradiotherapy remains the standard-of-care treatment for this patient population, it is still associated with a high rate of disease recurrence. Given the relatively high mutational burden of HNSCC, immunotherapy has emerged as a promising therapeutic strategy. The addition of PD-1 inhibitors to induction chemotherapy has been shown to improve antitumor responses without increasing treatment-related toxicity. In addition, radiotherapy can further potentiate systemic antitumor immune responses. Sintilimab, a PD-1 monoclonal antibody, has demonstrated robust antitumor activity across multiple solid malignancies. Early clinical evidence indicates a synergistic antitumor effect when combined with hypofractionated radiotherapy. Nevertheless, clinical data regarding the combination of sintilimab with chemoradiotherapy in locally advanced HNSCC remain limited. Accordingly, we designed a multicenter, single-arm phase II trial to evaluate the efficacy and safety of sintilimab in combination with definitive chemoradiotherapy for patients with locally advanced HNSCC.
Interventions
COMBINATION_PRODUCTHypofractionated Induction RT (5Gy×3) Followed by Sintilimab, Platinum-Based CCRT and Sintilimab
Induction therapy consists of two cycles of sintilimab injection combined with hypofractionated radiotherapy (5 Gy × 3), followed by sequential concurrent chemoradiotherapy delivered at 50 Gy in 25 fractions with two cycles of platinum-based chemotherapy (cisplatin, nedaplatin or carboplatin). Upon completion of chemoradiotherapy, patients are administered maintenance sintilimab injection for a minimum of six months.
Sponsors
Second Affiliated Hospital, Zhejiang University, School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Provide written informed consent and understand and agree to comply with study requirements and the study visit schedule. 2\. Male or female subjects aged ≥18 and ≤75 years at the time of signing the informed consent form. 3\. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1. 4\. Histologically or cytologically confirmed stage III IVB head and neck squamous cell carcinoma as assessed by the investigator. 5\. No prior systemic therapy for head and neck squamous cell carcinoma (including chemotherapy, EGFR monoclonal antibodies, anti PD 1 or anti PD L1 antibodies, anti CTLA 4 antibodies and other immune checkpoint inhibitors). 6\. At least one measurable target lesion per RECIST version 1.1 criteria. 7. Expected survival time ≥12 weeks. 8. Adequate bone marrow and organ function (no administration of any cellular/blood components, colony stimulating factors or cytokines within 14 days prior to laboratory testing): 1. Hematology: Absolute neutrophil count (ANC) ≥1.5×10⁹/L or within normal range; Platelet count (PLT) ≥100×10⁹/L; Hemoglobin (HGB) ≥90 g/L. 2. Hepatic function: Total bilirubin (TBIL) ≤1.5×ULN; For subjects with Gilbert's syndrome, TBIL ≤3×ULN; For subjects without liver metastasis, AST and ALT ≤2.5×ULN; For subjects with liver metastasis, AST and ALT ≤5×ULN; Albumin (ALB) ≥28 g/L. 3. Renal function: Serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance rate (CCR) ≥60 mL/min (calculated by Cockcroft Gault formula or measured via 24 hour urine collection); Urinalysis showing urinary protein \<2+. Subjects with baseline urinary protein ≥2+ must undergo 24 hour urine collection with 24 hour urinary protein \<1 g (if both assays are performed, the 24 hour urine result will be used for eligibility determination). 4. Coagulation function: International normalized ratio (INR) ≤1.5; Activated partial thromboplastin time (APTT) ≤1.5×ULN. 9\. Male and female subjects of non childbearing potential, or those who agree to use at least one highly effective contraceptive method during the study (starting 14 days prior to screening or first study drug administration, whichever occurs earlier, continuing for 180 days after the last dose of study drug).
Exclusion criteria
* 1\. History of hypersensitivity to PD 1 agents or platinum containing components. 2\. History or concurrent presence of other malignancies (except for malignancies cured with no relapse for more than 5 years, including basal cell carcinoma, carcinoma in situ of the cervix, and papillary thyroid carcinoma). 3\. Uncontrolled clinical cardiac symptoms or diseases, including: a. New York Heart Association (NYHA) class II or higher heart failure. b. Unstable angina pectoris. c. Myocardial infarction within the past 12 months. d. Clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention. 4\. Prior treatment history, including: 1. Previous treatment with anti PD 1, anti PD L1, or anti CTLA 4 antibodies. 2. Use of any investigational drug within 4 weeks prior to the first dose of study drug. 3. Concurrent participation in another clinical trial, unless it is an observational (non interventional) clinical study. 4. Patients requiring systemic corticosteroid therapy (≥10 mg prednisone equivalent dose per day) or other immunosuppressive agents within 2 weeks before the first dose of study drug, except for local inflammation, hypersensitivity, and prophylaxis for nausea and vomiting. Other special situations should be discussed with the investigator. In the absence of active autoimmune disease, inhaled or topical corticosteroids, or adrenal hormone replacement doses equivalent to \>10 mg/day prednisone are permitted. 5. Patients who have received anti tumor vaccines or live vaccines within 4 weeks prior to the first dose of study drug. 6. Patients who have undergone major surgery or sustained severe trauma within 4 weeks prior to the first dose of study drug. 5\. Not recovered to ≤ Grade 1 from previous anti tumor therapy according to Common Terminology Criteria for Adverse Events (CTCAE) (alopecia and residual neuropathy related to prior platinum based therapy are excluded), or failing to meet the levels specified in inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-year progression-free survival rate (1-year PFS rate) | 1 year from the date of enrollment | The proportion of patients who remain alive without disease progression (including local recurrence, regional recurrence, distant metastasis, or death) one year after the start of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From enrollment to the first documented tumor response assessment | Objective Response Rate (ORR) refers to the proportion of patients who achieve a measurable reduction in tumor burden, specifically those who experience a complete response (CR) or partial response (PR) according to standardized criteria (such as RECIST). |
| Progression-free survival(PFS) | From the date of enrollment until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 3 year. | Progression-free survival is the length of time from the start of treatment (or from randomization/enrollment) until the disease progresses or the patient dies from any cause, whichever occurs first. |
| Distant Metastasis-Free Survival (DMFS) | From the date of enrollment until the date of first documented distant metastasis or death from any cause, whichever occurs first, assessed up to 3 year. | Distant Metastasis-Free Survival (DMFS) is the length of time from the start of treatment (or from diagnosis/enrollment) until the first occurrence of distant metastasis or death from any cause, whichever happens first. |
| Overall Survival(OS) | From the date of enrollment until the date of death due to any cause, assessed up to 3 year. | Overall Survival(OS) is defined as the period from the date of first treatment administration to the date of death due to any cause. |
| Adverse events. | From enrollment to the end of treatment at 3 years. | The incidence, type, and severity of adverse events (AEs), serious AEs, and immune-related AEs (irAEs) were assessed in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 5.0). |
Countries
China
Contacts
CONTACTDongjun Dai, Doctor
Outcome results
None listed