Head & Neck Cancer, Head & Neck Squamous Cell Carcinoma, Postoperative Adjuvant Treatment
Conditions
Brief summary
A Multicenter, Randomized, Controlled, Open-Label, Phase III Clinical Trial.To evaluate the efficacy and safety of postoperative radiotherapy combined with Nimotuzumab followed by Benmelstobart in high-risk patients with head and neck squamous cell carcinoma who are ineligible for cisplatin chemotherapy. The primary endpoint is disease-free survival (DFS). A total of 185 patients will be enrolled in both the study group and the control group, respectively, with a total planned enrollment of 370 patients. Enrollment is expected to be completed within 2 years, followed by a 3-year follow-up period after the last patient is enrolled.
Interventions
DRUGBemcentinib
1200 mg on Day 1, every 3 weeks (Q3W) for a total of 17 cycles, initiated 3-4 weeks after completion of radiotherapy.
DRUGNimotuzumab
200 mg on Day 1, once weekly (QW) for a total of 7 cycles.
RADIATIONradiotherapy
Intensity-modulated radiation therapy (IMRT) will be administered at a total dose of 60-66 Gy (2 Gy per fraction, 30-33 fractions). A boost to a clearly defined high-risk area may be applied at the investigator's discretion.
Sponsors
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years. 2. Patients ineligible for cisplatin chemotherapy, defined as meeting any of the following:① Age \> 70 years;② Renal insufficiency (creatinine clearance \< 50 mL/min; criterion ⑩ below does not apply if this criterion is met);③ Severe tinnitus or hearing impairment (requiring hearing aid, or audiometry showing ≥ 25 dB loss at two consecutive frequencies);④ Unable to receive intravenous hydration (e.g., due to cardiac dysfunction or other comorbidities, as judged by the investigator);⑤ Neuropathy \> Grade 1;⑥ Patient refusal of chemotherapy. 3. Histologically confirmed locally advanced head and neck squamous cell carcinoma (AJCC 8th edition Stage III-IVB), including oral cavity cancer, HPV-negative/unrelated oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer. 4. Underwent radical surgery with at least one high-risk feature: Extracapsular extension (ECE) of lymph node metastasis; Close margin (\< 1 mm) or positive margin; * 4 metastatic lymph nodes, or multiple perineural invasions. 5. No evidence of distant metastasis on imaging. 6. Sufficient tumor tissue available for EGFR and PD-L1 testing; for oropharyngeal cancer, HPV/p16 testing is required (testing may be waived if results are already available). 7. Expected survival ≥ 6 months. 8. ECOG performance status 0-1. 9. Adequate hematologic function: WBC ≥ 3 × 10⁹/L; ANC ≥ 1.5 × 10⁹/L; Platelets ≥ 100 × 10⁹/L; Hemoglobin ≥ 90 g/L. 10. Adequate renal function:Serum creatinine ≤ 1.5 × ULN or creatinine clearance (CrCl) \> 50 mL/min (calculated by Cockcroft-Gault formula): Female: CrCl = (140 - Age) × Weight (kg) × 0.85 / (72 × Scr (mg/dL)) Male: CrCl = (140 - Age) × Weight (kg) × 1.00 / (72 × Scr (mg/dL)) 11. Adequate hepatic function: Total bilirubin ≤ 1.5 × ULN; AST ≤ 2.5 × ULN; ALT ≤ 2.5 × ULN. 12. Women of childbearing potential: negative serum or urine pregnancy test within 14 days before enrollment, and agreement to use effective contraception during the study.Male subjects: use effective contraception from the start of treatment until 180 days after the last study drug administration. 13. Voluntary participation in the study, signed written informed consent, good compliance, and willingness to comply with follow-up procedures.
Exclusion criteria
1. Prior radiotherapy for head and neck cancer before enrollment. 2. Prior treatment with similar immunological or targeted agents. 3. Participation in another interventional clinical trial within 30 days prior to screening. 4. Evidence of distant metastasis. 5. History of other malignancy within the previous 5 years, except cured carcinoma in situ of the cervix, non-melanoma skin cancer, localized differentiated thyroid cancer (papillary / follicular), localized prostate cancer, and ductal carcinoma in situ. 6. Uncontrolled concurrent medical conditions (e.g., heart failure, diabetes mellitus, hypertension, thyroid disease, psychiatric disorders, etc.). 7. Known HIV infection, active viral hepatitis, or active tuberculosis. 8. Major surgical procedure within 30 days before the first dose of study medication, or planned major surgery during the study. 9. Hypersensitivity to any study drug or their components. 10. Pregnancy (confirmed by serum or urine HCG test) or lactating women; subjects of childbearing potential unwilling or unable to use effective contraception (for both male and female subjects) until at least 6 months after the last study treatment. 11. Subjects considered inappropriate for study participation by the investigator. 12. Subjects unwilling to participate in the study or unable to provide written informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease-Free Survival (DFS | From enrollment until disease recurrence, metastasis, second primary cancer, or death from any cause, assessed up to 3 years after last patient enrolled |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From enrollment until death from any cause, assessed up to 3 years after last patient enrolled | — |
| Locoregional Recurrence-Free Survival (LRRFS) | From enrollment until first locoregional recurrence, assessed up to 3 years after last patient enrolled | — |
| Distant Metastasis-Free Survival (DMFS) | From enrollment until first distant metastasis, assessed up to 3 years after last patient enrolled | — |
| Change From Baseline in Global Quality of Life Score (EORTC QLQ-C30) | Up to 24 months. | Assessed using EORTC QLQ-C30 (V3) questionnaires.The EORTC QLQ-C30 is a 30-item validated questionnaire designed to assess the quality of life in cancer patients. It includes five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea/vomiting), a global health status/quality of life scale, and six single items assessing additional symptoms (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All scales and single items are scored on a range from 0 to 100. For the functional scales and global health status scale, higher scores indicate better quality of life or functioning. For the symptom scales and single items, higher scores indicate worse symptoms or greater severity. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the first dose of nimotuzumab through 30 days after the last dose (approximately 8 weeks total).] | Incidence of Treatment-Emergent Adverse Events (CTCAE 5.0） |
| Change From Baseline in Head and Neck-Specific Quality of Life Score (EORTC QLQ-H&N35) | Up to 24 months | Assessed using EORTC QLQ-H\&N35 questionnaires.The EORTC QLQ-H\&N35 is a 35-item validated questionnaire specifically designed to assess quality of life in head and neck cancer patients. It includes seven symptom scales (pain, swallowing, senses, speech, social eating, social contact, and sexuality) and eleven single items addressing additional head and neck-specific symptoms (e.g., teeth problems, mouth opening, dry mouth, sticky saliva, coughing, feeling ill, use of painkillers, nutritional supplements, feeding tube, weight loss, and weight gain). All scales and single items are scored on a range from 0 to 100, with higher scores indicating worse symptoms or greater severity. |
Countries
China
Contacts
CONTACTGuopei Zhu
CONTACTShengjin Dou
Outcome results
None listed