Neoadjuvant Personalized Anti-PD-1 and Anti-VEGFR Therapy in OSCC Patients

Официальное название

Neoadjuvant Personalized Anti-PD-1 Therapy With Combination of Anti-VEGFR Therapy in Locally Advanced and Resectable Oral Squamous Cell Carcinoma: A Randomized Controlled Phase II Trial

Обзор

To evaluate the efficacy of neoadjuvant anti-PD-1 plus anti-VEGFR therapy for patients with locally advanced and resectable oral squamous cell carcinoma, and the CPS\>10 in the biopsy samples.

Подробное описание

In the previous "Icemelting" trial, neoadjuvant anti-PD-1 plus anti-VEGFR therapy was used in 20 patients with locally advanced and resectable oral squamous cell carcinoma (OSCC), and the neoadjuvant therapy was well-tolerated, with no grade 3-4 toxicity. The MPR rate was 40% (8/20), including 5% (1/20) pathological complete response; furthermore, in the patients with CPS\>10, the MPR rate was 100%. As we know, the MPR might transfer to survival benefit in the patients received neoadjuvant therapy. Therefore, in this randomized phase II trial, we aimed to evaluate the survival benefit of neoadjuvant anti-PD-1 plus anti-VEGFR therapy in the patients with locally advanced OSCC and CPS\>10 (Icemelting-2 trial). A total of 46 patients will be enrolled in this trial, and the primary endpoint is 2-year disease-free survival rate. The neoadjuvant therapy arm will receive three cycles of Carrelizumab plus Apatinib with 14 days each, followed by the standard treatment of surgery and postoperative adjuvant therapy. The control arm will received the standard treatment of surgery and postoperative adjuvant therapy.

Вмешательства

• Препарат Camrelizumab (anti-PD-1 inhibitor)
  The patients will receive three cycles of Camrelizumab, with 14 days each. 200mg of Carrelizumab will be used intravenously on the first day of each cycle.
• Препарат Apatinib (anti-VEGFR inhibitor)
  The patients will receive Apatinib orally 250mg once a day from the first day of each cycle until the 9th day of the third cycle.

Первичные конечные точки

• 2-year disease-free survival rate [Срок оценки: 24 months]

Вторичные конечные точки (2)

• 2-year overall survival rate [Срок оценки: 24 months]
• Major pathological response [Срок оценки: 3 months]

Критерии участия

Критерии включения

• Age: 18 to 75
• Gender: Male and female
• ECOG Score: 0-2
• Histologically confirmed primary oral squamous cell carcinoma (including tongue, gingival, buccal, oral base, hard palate, posterior molar area)
• Clinical stage III/IVA (cT1-2/N1-2/M0 or cT3-4a/N0-2 /M0, AJCC 8th)
• The combined positive score (CPS score) of PD-L1 expression > 10
• Has signed informed consent

Критерии исключения

• Toxicity of ≥ grade 2 (CTCAE 5.0) that has not subsided due to previous anticancer therapy
• Obvious cardiovascular abnormalities (such as myocardial infarction, superior vena cava syndrome, ≥ grade 2 heart disease diagnosed according to the NYHA classification criteria within 3 months prior to enrollment)
• Active severe clinical infection (> NCI-CTCAE Version 5.0 level 2 infection)
• Uncontrollable hypertension (systolic blood pressure > after antihypertensive medication; 150mmHg and/or diastolic blood pressure > 90mmHg) or clinically significant (such as activity) cardiovascular disease, such as cerebrovascular accident (≤ 6 months before screening), myocardial infarction (≤ 6 months before screening), unstable angina, congestive heart failure rated class II or above by NYHA, or severe arrhythmias that cannot be controlled or have a potential impact on trial treatment
• Blood routine examination: WBC < 3,000/mm3, hemoglobin < 8g/L, platelet < 80,000/mm3
• Liver function: ALAT/ASAT > 2.5 times the normal upper limit, bilirubin > 1.5 times the normal upper limit
• Renal function: serum creatinine > 1.5 times the normal upper limit
• Has a history of maxillofacial and neck radiotherapy
• Pregnant or lactating women
• Participation in other clinical studies within 30 days prior to enrollment
• Other conditions that the investigator considers inappropriate for participation

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

• Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine — Шанхай

Идентификаторы

NCT: NCT05069857 · Icemelting-2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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