Locally Advanced Sinonasal Carcinoma
Conditions
Keywords
Locally Advanced, Sinonasal Carcinoma, neoadjuvant therapy, dual immune checkpoint inhibitors, Docetaxel, Cisplatin
Brief summary
The main objective of this prospective study is to evaluate the effectiveness and safety of a novel neoadjuvant therapy for patients with locally advanced sinonasal carcinoma (SNC). The treatment consists of the standard TP chemotherapy regimen (docetaxel and cisplatin) combined with dual immunotherapy (sintilimab and ipilimumab N01) administered before surgery. Researchers aim to determine the major pathological response (MPR) rate and long-term survival outcomes, while also exploring if this combination treatment approach can help better preserve critical facial and organ functions for SNC patients.
Detailed description
Currently, there is a lack of prospective phase II/III clinical evidence to guide the optimal treatment of locally advanced sinonasal carcinoma (SNC). Based on current clinical guidelines for head and neck squamous cell carcinoma (HNSCC), the investigators hypothesize that the combination of TP chemotherapy with dual immune checkpoint inhibitors (targeting PD-1 and CTLA-4) could significantly improve the major pathological response (MPR) and achieve superior organ function preservation in patients with locally advanced SNC. By evaluating the TP regimen combined with sintilimab and ipilimumab N01, this trial seeks to validate the feasibility of organ function preservation under this therapeutic modality. If successful, this treatment strategy will establish a novel precision treatment paradigm that effectively balances tumor control with organ function preservation, laying a solid foundation for subsequent phase III randomized controlled trials.
Interventions
Drug: Ipilimumab N01, 1mg/kg, D1C1. Drug: Sintilimab, 200mg, Q3W, C1C2C3. Drug: Docetaxel, 75mg/m2, Q3W, C1C2C3. Drug: Cisplatin, 60mg/m2, Q3W, C1C2C3. Procedure: Radical Surgery. Radiation: Adjuvant Radiotherapy.
Sponsors
Sun Yat-sen University
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Nanfang Hospital, Southern Medical University
First Affiliated Hospital, Sun Yat-Sen University
Zhujiang Hospital
Qingyuan People's Hospital
Guangdong Provincial People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A Simon's two-stage minimax design is adopted for this single-arm study to evaluate the efficacy and safety of the neoadjuvant combination therapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Disease Status: Newly diagnosed, pathologically confirmed locally advanced (AJCC 8th edition Stage III-IVA) sinonasal carcinoma (SNC). * Suitable for radical comprehensive treatment, with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1. * 18 to 75 years old. * Defined by the following laboratory test results obtained within 7 days prior to enrollment: Hematology (without blood transfusion or hematopoietic growth factor therapy within 14 days prior to testing): White blood cell (WBC) count ≥ 4.0 × 10\^9/L; Absolute neutrophil count (ANC) ≥ 2.0 × 10\^9/L; Platelet (PLT) count ≥ 100 × 10\^9/L. * Hepatic function: Total bilirubin \< 1.5 × upper limit of normal (ULN) (patients with known Gilbert's disease and serum bilirubin level ≤ 3 × ULN are eligible); Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase \< 1.5 × ULN. For patients positive for hepatitis B surface antigen (HBsAg), HBV-DNA must be ≤ 1000 IU/mL, and prophylactic antiviral therapy is required during the study. * Renal function: Serum creatinine \< 1.5 × ULN, or creatinine clearance ≥ 60 mL/min as calculated by the Cockcroft-Gault formula. * Coagulation: Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN. Patients receiving stable doses of anticoagulant therapy (e.g., low molecular weight heparin or warfarin) with an INR within the expected therapeutic range are eligible. * Thyroid function: Thyroid-stimulating hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels will be evaluated, and patients with normal T3 and T4 levels are eligible. * Contraception: Women of childbearing potential must agree to use highly effective contraceptive measures (e.g., intrauterine device, contraceptive pills, or condoms) during the treatment period and for at least 3 months after the last dose. They must have a negative serum or urine pregnancy test within 7 days prior to enrollment and must not be lactating. Male patients must agree to use highly effective contraceptive measures during the study period and for at least 3 months after the last dose. * Informed Consent: Voluntary participation with written informed consent signed.
Exclusion criteria
* History of other malignancies within the past 5 years, except for curatively treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, and papillary thyroid carcinoma. * Presence of residual measurable lesions or new tumor/metastasis according to RECIST 1.1 criteria, or deemed inoperable by a head and neck surgeon. * History of severe hypersensitivity reactions to other monoclonal antibodies or any components of the PD-1 inhibitors. * Prior and Concomitant Therapies: Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody (or any other antibody targeting T-cell costimulation or checkpoint pathways). * Use of high-dose glucocorticoids or traditional Chinese medicine with anti-tumor properties within 4 weeks prior to the first dose of the study drug. * Prior vaccination with an anti-tumor vaccine, or receipt of a live vaccine within 4 weeks prior to the first dose of the study drug. * Receipt of any investigational drug within 4 weeks prior to the first dose of the study drug. * Presence of comorbidities requiring long-term immunosuppressive therapy, or requiring systemic or local administration of corticosteroids at immunosuppressive doses prior to enrollment. * Concurrent Trials: Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up phase of an interventional study. * Recent Medical Events: Major surgery or severe trauma within 4 weeks prior to the first dose of the study drug. * Organ Transplantation: History of organ transplantation. * Autoimmune Diseases: Known or suspected active autoimmune disease. * Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS). * Concurrent positive HBsAg and positive HBV DNA copy number (quantitative detection ≥ 1000 cps/mL). Positive blood screening for chronic hepatitis C (HCV antibody positive). Concurrent HBV and HCV co-infection. (Note: Patients with normal liver function who have been on oral antiviral therapy for more than one week may be eligible). * Failure to meet relevant laboratory criteria within 7 days prior to enrollment; abnormal coagulation function (PT \> 16s, APTT \> 53s, TT \> 21s, Fib \< 1.5 g/L), bleeding tendency, or undergoing active thrombolytic or anticoagulant therapy. Significantly impaired cardiac, hepatic, pulmonary, renal, or bone marrow function. History of dementia or seizures. * Severe Infections: Severe infection (CTCAE \> Grade 2) within 4 weeks prior to the first dose of the study drug, such as severe pneumonia requiring hospitalization, bacteremia, or infectious complications; baseline chest imaging indicating active pulmonary inflammation; presence of signs and symptoms of infection within 2 weeks prior to the first dose of the study drug, or requiring oral or intravenous antibiotic therapy (excluding prophylactic use of antibiotics). * Pregnancy and Lactation: Pregnant or lactating women; women of childbearing potential who refuse to use effective contraceptive measures. * Compliance and Legal Capacity: Refusal or inability to sign the informed consent form; presence of personality or psychiatric disorders; lack of or limited civil capacity. * Other: Presence of any other treatment contraindications deemed inappropriate by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathological Response Rate(MPR) | From enrollment to the end of treatment at 9 weeks | Defined as the percentage of participants whose resected tumor specimens show ≤10% viable tumor cells upon microscopic examination following neoadjuvant therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 2 years | Defined as the proportion of patients who achieve a Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
| 2-Year Overall Survival (OS) Rate | 2 years from the start of treatment | Defined as the percentage of participants who are alive 2 years after the initiation of treatment. |
| Median Overall Survival (mOS) | Up to 2 years | Defined as the time from the start of treatment to death from any cause in 50% of the evaluated patients. |
| 2-Year Progression-Free Survival (PFS) Rate | 2 years from the end of the last treatment | Defined as the percentage of participants who remain alive and free of disease recurrence, new metastasis, or disease progression 2 years after the completion of the last treatment. |
| Median Progression-Free Survival (mPFS) | Up to 2 years | Defined as the time from the start of treatment until disease progression or death in 50% of the evaluable patients. |
| Duration of Response (DoR) | From the first documented CR or PR until the first documented tumor progression or death from any cause, assessed up to 2 years | Evaluated per RECIST v1.1. |
| Disease Control Rate (DCR) | Up to 2 years | Defined as the percentage of patients who achieve a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) following treatment. |
| R0 Resection Rate | At the time of surgery (assessed up to 4 weeks after completion of neoadjuvant therapy) | Defined as the percentage of patients achieving a complete tumor resection with microscopically negative margins. |
| Organ Functional Preservation Rate (OFPR) | At 2 years post-treatment | Defined as the percentage of living patients at 2 years post-treatment who do not require salvage radical surgery and successfully preserve major physiological functions. Patients must meet all 4 conditions: Maxilla \& Oral: No total maxillectomy (limited/scaffold-preserving excision allowed); no permanent tube feeding; intelligible speech; no severe trismus (mouth opening \>2.5cm). Orbit \& Vision: No enucleation/orbital exenteration; ipsilateral vision better than light perception (≥0.05); no intractable diplopia, severely restricted eye movement, or eyelid dysfunction causing exposure keratitis. Skull Base \& Neurological: No massive cranial/dural defect from extensive resection; no persistent CSF leak; no severe treatment-induced CNS complications. Appearance: No obvious facial collapse or disfigurement; adequate subjective satisfaction (FACE-Q scale); no external facial prosthesis required. |
| Change in Quality of Life Scores (QOL) | Baseline and up to 2 years | The psychological state and overall quality of life of the patients will be evaluated using the QOL-V30 questionnaire. Higher scores generally represent a higher quality of life or level of functioning. |
Contacts
CONTACTKaiyue Mao
CONTACTXiaoyun Feng
PRINCIPAL_INVESTIGATORXuekui Liu
Sun Yat-Sen University Cancer Center
PRINCIPAL_INVESTIGATORChunyan Chen
Sun Yat-Sen University Cancer Center
Outcome results
None listed