Surgery With or Without Neoadjuvant Treatment of SBRT Plus Chemoimmunotherapy in Resectable Locally Advanced Oral and HPV-unrelated Oropharyngeal Squamous Cell Carcinoma

February 4, 2026 updated by: Fang-Yun Xie, Sun Yat-sen University

SBRT Followed by Neoadjuvant Chemoimmunotherapy Before Surgery in Resectable Locally Advanced Oral and HPV-unrelated Oropharyngeal Squamous Cell Carcinoma: a Randomized Controlled Phase III Trial

The objective of this study is to evaluate the efficacy of neoadjuvant stereotactic body radiation therapy (SBRT) in combination with chemotherapy and immunotherapy, prior to radical surgery, in enhancing the 2-year event-free survival rate and overall survival rate in patients diagnosed with locally advanced oral or HPV-unrelated oropharyngeal cancer.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

184

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat-sen University Cancer Center
        • Contact:
        • Principal Investigator:
          • Ming Song, M.D.
        • Principal Investigator:
          • Fang-Yun Xie, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

The inclusion criteria for this study are as follows:

  • Histologically and/or cytologically confirmed treatment-naïve oral squamous cell carcinoma or HPV-negative oropharyngeal squamous cell carcinoma.
  • Clinical stage III -Ⅳa (8th edition of AJCC).
  • Age: 18 to 75 years old.
  • According to the Eastern Cooperative Oncology Group (ECOG) criteria (with a performance status score of 0 or 1).
  • Good organ function.
  • Expected survival time: ≥ 3 months.
  • The patient has signed the informed consent form and is willing and able to comply with the study's scheduled visits, treatment plans, laboratory tests, and other research procedures.
  • Females of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to enrolment and must agree to use highly effective contraceptive measures during the study period and for at least 60 days after the last dose (including chemotherapeutic drugs and Tislelizumab).
  • If the female partner of a male subject is still of childbearing potential, the male subject must agree to use highly effective contraceptive measures during the study period and for at least 60 days after the last dose.

Exclusion Criteria:

  • Patients with concurrent other malignant tumors
  • Patients with known or suspected autoimmune diseases, including dementia and epilepsy.
  • Patients with severe mental disorders at the same time
  • Patients with necrotic lesions who are assessed by the investigator as having a risk of massive hemorrhage
  • Patients with severe heart disease or pulmonary dysfunction, and those with cardiac or pulmonary function grade ≤ 3 (grade 3 inclusive)
  • Patients with laboratory test results that do not meet the relevant criteria within 7 days prior to enrollment
  • Received systemic or local glucocorticoid therapy within 4 weeks prior to enrollment
  • Patients with comorbidities requiring long-term treatment with immunosuppressive drugs, or requiring systemic or local administration of corticosteroids at immunosuppressive doses.
  • Patients with active tuberculosis (TB), who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year prior to screening.
  • A history of prior use of anti-Tislelizumab, anti-PD-L1 antibodies, anti-PD-L2 antibodies, or anti-CTLA-4 antibodies (or any other antibodies targeting T-cell co-stimulation or checkpoint pathways).
  • Subjects with any active autoimmune diseases or a history of autoimmune diseases (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism); subjects with vitiligo or those whose childhood asthma has been completely relieved and who do not require any intervention in adulthood are eligible for enrollment; those with asthma requiring medical intervention with bronchodilators are not eligible for enrollment.
  • HIV-positive subjects
  • Positive for HBsAg with concurrent positive HBV DNA copy number (quantitative test ≥ 1000 cps/ml); positive for chronic hepatitis C on blood screening (HCV antibody positive)
  • Received any anti-infective vaccines (such as influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment
  • Pregnant women with positive pregnancy test results among females of childbearing potential and lactating women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoadjuvant treatment followed by surgery arm
Initially, the patient underwent neoadjuvant treatment, including stereotactic body radiotherapy (SBRT) followed by chemoimmunotherapy of Tislelizumab (200 mg), Docetaxel (75 mg/m²), and Cisplatin (75 mg/m²). A subsequent imaging re-examination is to be performed for assessment two weeks after the last chemotherapy cycle. Finally, curative surgical resection should be performed 3-4 weeks after the last chemotherapy cycle, followed by adjuvant postoperative radiotherapy or chemoradiotherapy.
Combination product: Neoadjuvant treatment of SBRT plus chemoimmunotherapy followed by surgery and postoperative radiotherapy or chemoradiotherapy
The patient was initially subjected to a neoadjuvant treatment regime, encompassing stereotactic body radiotherapy (SBRT) and chemoimmunotherapy. The SBRT was administered with a dose of 6 Gy per fraction to the primary tumour and metastatic lymph nodes, administered every other day for a total of three fractions. Following this, a period of one to two weeks was to elapse before the initiation of Tislelizumab (200 mg), Docetaxel (75 mg/m²), and Cisplatin (75 mg/m²), on a three-week cycle, for a total of two cycles. A subsequent imaging re-examination was to be performed for assessment two weeks after the final chemotherapy cycle. Finally, curative surgical resection was to be performed 3-4 weeks after the final chemotherapy cycle, followed by adjuvant postoperative radiotherapy or chemoradiotherapy with cisplatin at a dose of 100 mg/m² for two cycles.
Active Comparator: Surgery arm
Radical surgery followed by postoperative radiotherapy or chemoradiotherapy.
Combination product: Surgery and postoperative radiotherapy or chemoradiotherapy
Radical surgery followed by postoperative radiotherapy or chemoradiotherapy with cisplatin at a dose of 100 mg/m² for three cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-year event-free survival
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to two years.
The time interval from randomization to the occurrence of imaging tumor progression during the neoadjuvant treatment stage that makes surgery impossible, or postoperative imaging or biopsy results show local tumor recurrence, lymph node recurrence, distant metastasis, or death for any cause.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to two years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-year overall survival
Time Frame: From date of randomization until the date of death from any cause, assessed up to two years.
The time interval from random start to death for any cause.
From date of randomization until the date of death from any cause, assessed up to two years.
MPR
Time Frame: Three weeks after surgery
Proportion of patients with ≤10% viable tumor cells identified per AJCC/CAP Tumor Regression Grading (TRG) protocol evaluation of surgical specimens.
Three weeks after surgery
pCR
Time Frame: Three weeks after surgery
Proportion of patients with no viable tumor cells identified upon complete and systematic evaluation of postoperative specimens under the AJCC/CAP Tumor Regression Grading (TRG) protocol, including microscopic examination of all sampled primary tumor sites and regional lymph nodes.
Three weeks after surgery
Mandibular Preservation Rate
Time Frame: On the day of surgery
Proportion of oral cancer patients retaining mandibular continuity after primary tumor resection.
On the day of surgery
Incidence rates of AEs (Adverse Events) and SAEs (Serious Adverse Events)
Time Frame: Through study completion, an average of 3 year
Percentage of patients with adverse events ≥ Grade 3 among all treated patients.
Through study completion, an average of 3 year
Quality of life assessment
Time Frame: Postoperatively at 24 months
Quality of life was assessed using the EORTC QLQ-C30 scale at postoperative time point of 2 year.
Postoperatively at 24 months
Quality of life assessment
Time Frame: Postoperatively at 24 months
Quality of life was assessed using the QLQ-H&N35 scale at postoperative time point of 2 year
Postoperatively at 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Fang-Yun Xie, M.D., Sun Yat-sen University
  • Principal Investigator: Ming Song, M.D., Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 24, 2026

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

January 16, 2026

First Submitted That Met QC Criteria

February 4, 2026

First Posted (Actual)

February 11, 2026

Study Record Updates

Last Update Posted (Actual)

February 11, 2026

Last Update Submitted That Met QC Criteria

February 4, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B2025-532-X01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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