Neoadjuvant Immunochemotherapy and Postoperative Adjuvant Immunotherapy for Head and Neck Squamous Cell Carcinoma Invading the Skull Base

Official title

Tislelizumab Combined With Chemotherapy for Neoadjuvant Immunochemotherapy and Postoperative Adjuvant Therapy for Head and Neck Squamous Cell Carcinoma Invading the Skull Base: A Prospective, Single-arm, Phase II Clinical Study

Overview

This prospective, single-arm, Phase II clinical trial aims to evaluate the efficacy and safety of tislelizumab combined with chemotherapy as neoadjuvant therapy and postoperative adjuvant immunotherapy in patients with skull base-invading head and neck squamous cell carcinoma. The primary objectives are to address the following questions: * What are the objective response rate and pathological response of tislelizumab combined with chemotherapy as neoadjuvant therapy in patients with skull base-invading head and neck squamous cell carcinoma? * Can neoadjuvant therapy convert unresectable skull base-invading head and neck squamous cell carcinoma into a resectable condition? * Can adjuvant immunotherapy after neoadjuvant therapy prolong patients' recurrence-free survival and overall survival? The researchers will administer neoadjuvant therapy (tislelizumab combined with chemotherapy) and adjuvant immunotherapy to patients with skull base-invading head and neck squamous cell carcinoma and assess the treatment's efficacy and safety. Participants will: * Receive neoadjuvant therapy every 3 weeks (tislelizumab 200mg on Day 1, nab-paclitaxel 260mg/m² on Day 1, cisplatin 75mg/m² on Days 1-3) for 3 cycles. * Undergo surgical treatment within 3 weeks after completing neoadjuvant therapy. * Receive (chemo)radiotherapy 4-6 weeks after surgery. * Receive adjuvant immunotherapy (tislelizumab 200mg) every 3 weeks after (chemo)radiotherapy for 8 cycles.

Interventions

• Procedure Neoadjuvant chemoimmunotherapy
  * Neoadjuvant therapy is administered every 3 weeks (Tislelizumab 200mg D1, Nab Paclitaxel 260mg/m² D1, Cisplatin 75mg/m² D1-3) for a total of 3 cycles. * Surgical treatment is performed within 3 weeks after completing neoadjuvant therapy. * Postoperative (chemo)radiotherapy is initiated 4-6 weeks after surgery. * Following (chemo)radiotherapy, adjuvant immunotherapy (Tislelizumab 200mg) is administered every 3 weeks for a total of 8 cycles.
• Drug Tislelizumab Nab paclitaxel
  Neoadjuvant therapy is administered every 3 weeks (Tislelizumab 200mg D1, Nab Paclitaxel 260mg/m² D1, Cisplatin 75mg/m² D1-3) for a total of 3 cycles.

Primary outcome measures

• Objective response rate [Time frame: Within 3 weeks after completion of neoadjuvant therapy]

Secondary outcome measures (8)

• Number of participants with Adverse Events [Time frame: Until 21 days after the end of the study]
• Pathologic Efficacy [Time frame: Perioperative]
• Clinical Downstaging Rate [Time frame: Within 3 weeks after completion of neoadjuvant therapy.]
• Surgical Conversion Rate [Time frame: Within 3 weeks after completion of neoadjuvant therapy.]
• R0 Resection Rate [Time frame: Perioperative]
• Organ Preservation Rate [Time frame: Perioperative]
• Recurrence-Free Survival [Time frame: Until cancer recurrence or death or the last follow-up, whichever came first, assessed up to 24 months]
• Overall Survival [Time frame: Until death from any cause or the last follow-up, whichever came first, assessed up to 24 months]

Eligibility criteria

Inclusion criteria

• Age 18 to 80 years, regardless of gender;
• Histologically confirmed squamous cell carcinoma (including gingiva, buccal mucosa, palate, oropharynx, maxillary sinus, or maxilla/mandible) with radiological evidence of skull base invasion;
• Measurable tumor lesions (meeting RECIST v1.1 criteria);
• Treatment-naïve primary T4b-stage patients (N any, per AJCC 8th Edition, 2017);
• ECOG PS score: 0-1;
• Medically fit for surgery and chemotherapy, with no surgical contraindications;
• Women of childbearing potential (18-49 years) must have a negative pregnancy test within 7 days before treatment. Sexually active men and women must agree to use effective contraception during the trial and for 3 months after treatment cessation;
• Willing to provide written informed consent and comply with scheduled follow-ups, treatments, lab tests, and other study requirements.

Exclusion criteria

• Previous anti-tumor treatments including chemotherapy, radiotherapy, or immunotherapy; Refusal to sign informed consent;
• Patients who refuse the study treatment protocol; patients unable to complete treatment as planned; or patients unable to comply with regular follow-up due to psychological, social, familial or geographical reasons;
• Patients with known allergies to any study medications;
• Patients with poor systemic conditions unfit for treatment: as determined by routine tests (complete blood count, blood biochemistry, ECG, chest X-ray, etc.). Poor systemic conditions include: hemoglobin <60g/L, WBC <3.0×10⁹/L, platelets <80×10⁹/L, or serum creatinine >133μmol/L - such patients may be recommended for conservative treatment;
• Patients with autoimmune diseases requiring long-term immunosuppressive or corticosteroid therapy;
• Pregnant or lactating women (pregnancy testing should be considered for sexually active women of childbearing potential);
• Patients with current or previous malignancies (except adequately treated non-melanoma skin cancer, cervical carcinoma in situ, or papillary thyroid carcinoma);
• Participation in other clinical trials within 30 days prior to enrollment;
• Other conditions that may compromise patient safety or compliance as assessed by investigators, including: severe comorbidities (including psychiatric disorders), significantly abnormal laboratory results, or other high-risk familial/social factors.

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

China · 1 center

• Hospital of Stomatology, Sun Yat-sen University — Guangzhou

Publications

• Zhang Z, Wu B, Peng G, Xiao G, Huang J, Ding Q, Yang C, Xiong X, Ma H, Shi L, Yang J, Hong X, Wei J, Qin Y, Wan C, Zhong Y, Zhou Y, Zhao X, Leng Y, Zhang T, Wu G, Yao M, Zhang X, Yang K. Neoadjuvant Chemoimmunotherapy for the Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: A Single-Arm Phase 2 Clinical Trial. Clin Cancer Res. 2022 Aug 2;28(15):3268-3276. doi: 10.1158/1078-0432 PMID 35766967
• Patel SA, Gibson MK, Deal A, Sheth S, Heiling H, Johnson SM, Douglas K, Flores M, Blumberg J, Lumley C, Yarbrough WG, Shen C, Chera BS, Bauman JR, Hackman T, Weiss J. A phase 2 study of neoadjuvant chemotherapy plus durvalumab in resectable locally advanced head and neck squamous cell carcinoma. Cancer. 2023 Nov 1;129(21):3381-3389. doi: 10.1002/cncr.34930. Epub 2023 Jul 3. PMID 37395170
• Wu D, Li Y, Xu P, Fang Q, Cao F, Lin H, Li Y, Su Y, Lu L, Chen L, Li Y, Zhao Z, Hong X, Li G, Tian Y, Sun J, Yan H, Fan Y, Zhang X, Li Z, Liu X. Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial. Nat Commun. 2024 Mar 11;15(1):2177. doi: 10.1038/s41467-024-46444-z. PMID 38467604
• Zhong LP, Zhang CP, Ren GX, Guo W, William WN Jr, Sun J, Zhu HG, Tu WY, Li J, Cai YL, Wang LZ, Fan XD, Wang ZH, Hu YJ, Ji T, Yang WJ, Ye WM, Li J, He Y, Wang YA, Xu LQ, Wang BS, Kies MS, Lee JJ, Myers JN, Zhang ZY. Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous PMID 23129742
• Sharma P, Stecklein SR, Yoder R, Staley JM, Schwensen K, O'Dea A, Nye L, Satelli D, Crane G, Madan R, O'Neil MF, Wagner J, Larson KE, Balanoff C, Kilgore L, Phadnis MA, Godwin AK, Salgado R, Khan QJ, O'Shaughnessy J. Clinical and Biomarker Findings of Neoadjuvant Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer: NeoPACT Phase 2 Clinical Trial. JAMA Oncol. 2024 Feb 1;10 PMID 37991778
• Romero D. Neoadjuvant chemoimmunotherapy is effective in locally advanced cervical cancer. Nat Rev Clin Oncol. 2024 Feb;21(2):84. doi: 10.1038/s41571-023-00855-x. No abstract available. PMID 38110599
• Sepesi B, Swisher SG. Role of neoadjuvant chemoimmunotherapy for resectable NSCLC. Nat Rev Clin Oncol. 2022 Aug;19(8):497-498. doi: 10.1038/s41571-022-00647-9. No abstract available. PMID 35585121
• Masarwy R, Kampel L, Horowitz G, Gutfeld O, Muhanna N. Neoadjuvant PD-1/PD-L1 Inhibitors for Resectable Head and Neck Cancer: A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg. 2021 Oct 1;147(10):871-878. doi: 10.1001/jamaoto.2021.2191. PMID 34473219

Identifiers

NCT: NCT07145931 · GHKQ-202503-L011

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗