Head and Neck Cancer Squamous Cell Carcinoma, Neoadjuvant Chemoimmunotherapy, Objective Response Rate, Skull Base--Cancer
Conditions
Keywords
Head and Neck Cancer Squamous Cell Carcinoma, Skull Base--Cancer, Neoadjuvant Chemoimmunotherapy, Objective response rate
Brief summary
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
PROCEDURENeoadjuvant 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.
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.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | Within 3 weeks after completion of neoadjuvant therapy | Objective Response Rate (ORR) is a pivotal efficacy endpoint in oncology therapeutic evaluation, defined as the proportion of patients whose tumor burden shrinks to a prespecified threshold (achieving either complete or partial response). This metric is measured using internationally standardized criteria (RECIST 1.1), with radiographic imaging to monitor changes in the sum of target lesion diameters. Based on Standardized Criteria (e.g., RECIST 1.1). Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥30% decrease in tumor size (sum of target lesions). ORR = CR + PR (expressed as a percentage). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Efficacy | Perioperative | The percentage of residual tumor cells in tumor bed of pathological specimens after surgery. Pathological complete response (pCR) refers to tumors the absence of any viable tumor cells within the tumor bed. Major pathological response (MPR) is defined as 10% or fewer residual viable tumor cells within the tumor bed. |
| Clinical Downstaging Rate | Within 3 weeks after completion of neoadjuvant therapy. | The proportion of patients with reduction in clinical TNM stage. |
| Surgical Conversion Rate | Within 3 weeks after completion of neoadjuvant therapy. | The proportion of patients with initially unresectable tumors that become resectable after treatment. |
| Number of participants with Adverse Events | Until 21 days after the end of the study | To evaluate the adverse events during the study period according to the NCI-CTCAE, version 5.0, including vital signs, physical examination, laboratory tests, changes in ECOG score, etc., as well as adverse events and serious adverse events, are calculated to the incidence of adverse events and serious adverse events. |
| Organ Preservation Rate | Perioperative | The proportion of patients who, despite pretreatment tumor invasion into critical organs (e.g., eyeball, internal carotid artery, dura mater), successfully retain the involved organ while still achieving R0 resection. |
| Recurrence-Free Survival | Until cancer recurrence or death or the last follow-up, whichever came first, assessed up to 24 months | The time from enrollment until cancer recurrence or death from any cause. |
| Overall Survival | Until death from any cause or the last follow-up, whichever came first, assessed up to 24 months | The time from enrollment until death from any cause or the last follow-up. |
| R0 Resection Rate | Perioperative | The proportion of patients achieving complete tumor removal with microscopically negative margins (no residual tumor cells). |
Countries
China
Contacts
Primary ContactYujie Liang
Outcome results
None listed