Postoperative Radiotherapy Combined With Nimotuzumab Followed by Benmelstobart in High-Risk Patients With Head and Neck Squamous Cell Carcinoma

Официальное название

A Multicenter, Randomized, Controlled, Open-Label, Phase III Clinical Trial 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

Обзор

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.

Вмешательства

• Препарат Bemcentinib
  1200 mg on Day 1, every 3 weeks (Q3W) for a total of 17 cycles, initiated 3-4 weeks after completion of radiotherapy.
• Препарат Nimotuzumab
  200 mg on Day 1, once weekly (QW) for a total of 7 cycles.
• Лучевая терапия radiotherapy
  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.

Первичные конечные точки

• Disease-Free Survival (DFS [Срок оценки: From enrollment until disease recurrence, metastasis, second primary cancer, or death from any cause, assessed up to 3 years after last patient enrolled]

Вторичные конечные точки (6)

• Overall Survival (OS) [Срок оценки: From enrollment until death from any cause, assessed up to 3 years after last patient enrolled]
• Locoregional Recurrence-Free Survival (LRRFS) [Срок оценки: From enrollment until first locoregional recurrence, assessed up to 3 years after last patient enrolled]
• Distant Metastasis-Free Survival (DMFS) [Срок оценки: 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) [Срок оценки: Up to 24 months.]
• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Срок оценки: From the first dose of nimotuzumab through 30 days after the last dose (approximately 8 weeks total).]]
• Change From Baseline in Head and Neck-Specific Quality of Life Score (EORTC QLQ-H&N35) [Срок оценки: Up to 24 months]

Критерии участия

Критерии включения

• Age ≥ 18 years.
• 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.
• 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.
• 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.
• No evidence of distant metastasis on imaging.
• 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).
• Expected survival ≥ 6 months.
• ECOG performance status 0-1.
• Adequate hematologic function:

WBC ≥ 3 × 10⁹/L; ANC ≥ 1.5 × 10⁹/L; Platelets ≥ 100 × 10⁹/L; Hemoglobin ≥ 90 g/L.

• 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))

• Adequate hepatic function:

Total bilirubin ≤ 1.5 × ULN; AST ≤ 2.5 × ULN; ALT ≤ 2.5 × ULN.

• 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.
• Voluntary participation in the study, signed written informed consent, good compliance, and willingness to comply with follow-up procedures.

Критерии исключения

• Prior radiotherapy for head and neck cancer before enrollment.
• Prior treatment with similar immunological or targeted agents.
• Participation in another interventional clinical trial within 30 days prior to screening.
• Evidence of distant metastasis.
• 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.
• Uncontrolled concurrent medical conditions (e.g., heart failure, diabetes mellitus, hypertension, thyroid disease, psychiatric disorders, etc.).
• Known HIV infection, active viral hepatitis, or active tuberculosis.
• Major surgical procedure within 30 days before the first dose of study medication, or planned major surgery during the study.
• Hypersensitivity to any study drug or their components.
• 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.
• Subjects considered inappropriate for study participation by the investigator.
• Subjects unwilling to participate in the study or unable to provide written informed consent.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai 9th people's hospital — Шанхай

Идентификаторы

NCT: NCT07445048 · BPL-Nim-SCCHN-91

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗