Neoadjuvant Docetaxel, Cisplatin, and Dual Immunotherapy for Sinonasal Carcinoma

Official title

A Multicenter, Single-Arm, Phase II Trial of Neoadjuvant Docetaxel and Cisplatin Combined With Dual Immunotherapy for Locally Advanced Sinonasal Carcinoma (PANDA Study)

Overview

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 Neoadjuvant Chemo-Immunotherapy
  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.

Primary outcome measures

• Major Pathological Response Rate(MPR) [Time frame: From enrollment to the end of treatment at 9 weeks]

Secondary outcome measures (10)

• Objective Response Rate (ORR) [Time frame: Up to 2 years]
• 2-Year Overall Survival (OS) Rate [Time frame: 2 years from the start of treatment]
• Median Overall Survival (mOS) [Time frame: Up to 2 years]
• 2-Year Progression-Free Survival (PFS) Rate [Time frame: 2 years from the end of the last treatment]
• Median Progression-Free Survival (mPFS) [Time frame: Up to 2 years]
• Duration of Response (DoR) [Time frame: From the first documented CR or PR until the first documented tumor progression or death from any cause, assessed up to 2 years]
• Disease Control Rate (DCR) [Time frame: Up to 2 years]
• R0 Resection Rate [Time frame: At the time of surgery (assessed up to 4 weeks after completion of neoadjuvant therapy)]
• Organ Functional Preservation Rate (OFPR) [Time frame: At 2 years post-treatment]
• Change in Quality of Life Scores (QOL) [Time frame: Baseline and up to 2 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07645846 · 2026-FXY-123

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗