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

NCT07402538 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: B2025-532-X01
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Oral Cancer; Oropharyngeal Cancer

Keywords

SBRT; neoadjuvant therapy; locally advanced oral/oropharyngeal cancer

Outcome Measures

Primary Outcomes (1)

• 2-year event-free survival

  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 Outcomes (7)

• 2-year overall survival

  From date of randomization until the date of death from any cause, assessed up to two years.

• MPR

  Three weeks after surgery

• pCR

  Three weeks after surgery

• Mandibular Preservation Rate

  On the day of surgery

• Incidence rates of AEs (Adverse Events) and SAEs (Serious Adverse Events)

  Through study completion, an average of 3 year

Study Arms (2)

Neoadjuvant treatment followed by surgery arm

EXPERIMENTAL

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

Surgery arm

ACTIVE COMPARATOR

Radical surgery followed by postoperative radiotherapy or chemoradiotherapy.

Combination Product: Surgery and postoperative radiotherapy or chemoradiotherapy

Interventions

Surgery and postoperative radiotherapy or chemoradiotherapy COMBINATION_PRODUCT

Radical surgery followed by postoperative radiotherapy or chemoradiotherapy with cisplatin at a dose of 100 mg/m² for three cycles.

Surgery arm

Neoadjuvant treatment of SBRT plus chemoimmunotherapy followed by surgery and postoperative radiotherapy or chemoradiotherapy COMBINATION_PRODUCT

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.

Neoadjuvant treatment followed by surgery arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Mouth Neoplasms; Oropharyngeal Neoplasms

Interventions

Chemoradiotherapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Fang-Yun Xie, M.D.

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

• Ming Song, M.D.

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pu-Yun OuYang, M.D.

CONTACT

020-87342925; ouyangpy@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: January 16, 2026
• First Posted: February 11, 2026
• Study Start: February 24, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)