Clinical trial NCT06861712: Chemoimmunotherapy With or Without SBRT Before Surgery for Locally Advanced Oral and Oropharyngeal Cancer
Official title: Neoadjuvant Chemoimmunotherapy With or Without SBRT Followed by Surgery for Locoregionally Advanced Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: A Phase II Randomized Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Oral Squamous Cell Carcinoma (OSCC)
Oropharyngeal Squamous Cell Carcinoma (SCC)
Stereotactic Body Radiation Therapy (SBRT)
Keywords: Oral Squamous Cell Carcinoma (OSCC)
Oropharyngeal Squamous Cell Carcinoma (SCC)
Stereotactic Body Radiation Therapy (SBRT)
Toripalimab
Phase II Clinical Trial
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Hospital of Stomatology, Sun Yat-Sen University
First posted: 2025-03-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study, participants will be randomly assigned to either the experimental group or the control group. The experimental group will first receive SBRT (6Gy\*3 fractions) to treat the primary tumor and metastatic lymph nodes. This will be followed by a combination of Toripalimab, Docetaxel, and Cisplatin for three cycles, every three weeks. The control group will receive the same combination of Toripalimab, Docetaxel, and Cisplatin for three cycles, every three weeks, but without SBRT. After the final round of chemotherapy, all participants will have imaging scans and, three weeks later, undergo surgery. After surgery, they may also receive additional radiotherapy with or without chemotherapy. Patients can also choose whether to continue treatment with Toripalimab after surgery.

Detailed description: Participants will be randomly assigned to the experimental group and the control group. The experimental group will first receive SBRT (Stereotactic Body Radiotherapy) for the primary tumor and positive lymph nodes (prescribed dose: 6 Gy × 3 fractions, once every other day). One to two weeks after SBRT, they will receive 240 mg of Toripalimab + 75 mg/m² of Docetaxel + 75 mg/m² of Cisplatin, administered every 3 weeks for 3 cycles. The control group will receive 240 mg of Toripalimab + 75 mg/m² of Docetaxel + 75 mg/m² of Cisplatin, administered every 3 weeks for 3 cycles. Both groups will undergo imaging assessment 2 weeks after the final chemotherapy cycle. Three weeks after the last chemotherapy cycle, participants will receive curative surgery. Postoperative adjuvant radiotherapy ± chemotherapy will be administered according to preoperative staging and postoperative pathological characteristics. Patients may also choose to continue maintenance treatment with Toripalimab after surgery.

Eligibility criteria: Inclusion Criteria:

1. Oral/oropharyngeal squamous cell carcinoma confirmed by histology and/or cytology.
2. Clinical stage: resectable oral/oropharyngeal squamous cell carcinoma stage III-IVa (AJCC 8th edition)
3. Age: 18-65 years old.
4. According to the Eastern Cooperative Oncology Group (ECOG) criteria (performance status score of 0 or 1).
5. Good organ function:

   A. Hematology: WBC ≥ 4000/μL, neutrophil ≥ 2.000/μL, hemoglobin ≥ 9g/dL, platelet ≥ 100000/μL; B. Liver function: bilirubin ≤ 1.5 times the upper limit of normal (ULN) (patients with known Gilbert's disease and serum bilirubin level ≤ 3 times ULN can be included), AST and ALT ≤ 3 times, and alkaline phosphatase ≤ 3 times ULN; albumin ≥ 3g/dL; C. International normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤ 1.5 times; D. Renal function: serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60mL/min according to the Cockcroft-Gault formula.
6. Expected survival ≥ 3 months.
7. The patient has signed an informed consent form and is willing and able to comply with the study visits, treatment plans, laboratory tests and other study procedures.
8. Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days before enrollment and must agree to take effective contraceptive measures during the study and for at least 60 days after the last dose (including chemotherapy drugs and Teplizumab).
9. If the female partner of the male subject is still of childbearing potential, the male subject must agree to take effective contraceptive measures during the study and for at least 60 days after the last dose.

Exclusion Criteria:

1. Patients with other malignant tumors.
2. Patients with known or suspected autoimmune diseases, including dementia and epilepsy.
3. Patients with severe mental illness.
4. Patients with necrotic lesions and who are assessed by the researchers to be at risk of major bleeding.
5. Patients with severe heart disease, pulmonary dysfunction, heart function and pulmonary function below grade 3 (including grade 3).
6. Patients whose laboratory test values do not meet the relevant standards within 7 days before enrollment.
7. Patients who have received systemic or local glucocorticoid treatment within 4 weeks before enrollment.
8. Patients with complications that require long-term use of immunosuppressive drugs or systemic or local use of corticosteroids with immunosuppressive effects.
9. Patients with active pulmonary tuberculosis (TB) who are currently receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening.
10. Previous use of anti-toripalimab, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell co-stimulation or checkpoint pathway).
11. Subjects with any active autoimmune disease or history of autoimmune disease (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; patients with vitiligo or complete remission of asthma in childhood and no need for any intervention as adults can be included; patients with asthma requiring medical intervention with bronchodilators cannot be included).
12. HIV positive.
13. HBsAg positive and HBVDNA copy number positive (quantitative detection ≥1000cps/ml); positive blood screening for chronic hepatitis C (HCV antibody positive).
14. Any anti-infection vaccine (such as influenza vaccine, varicella vaccine, etc.) received within 4 weeks before enrollment.
15. Women of childbearing age with positive pregnancy test and breastfeeding women.

Primary outcomes:
measure: Pathological Complete Response (pCR)
timeFrame: 2 weeks after the surgery
Secondary outcomes:
measure: Major Pathological Response (MPR)
timeFrame: 2 weeks after the surgery
measure: Objective response rate (ORR)
timeFrame: two weeks after the chemoimmunotherapy
measure: Disease-free survival (DFS):
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2 years
measure: Mandibular preservation rate:
timeFrame: immediately after the surgery
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: one month after the postoperative radiotherapy
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Radiation Oncology, Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
References:
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