Pembrolizumab in Combination With Low-dose PFas Neoadjuvant Treatment for Locally Advanced HNSCC

Официальное название

Safety and Efficacy of Pembrolizumab in Combination With Low-dose PF (Cisplatin and 5-Fluorouracil) as Neoadjuvant Treatment for Locally Advanced Head and Neck Squamous Cell Carcinoma: a Multi-center, Single-arm Clinical Study Trial

Обзор

A phase Ⅱ open label multi-cencter clinical trail to evaluate the efficacy and safety of pembrolizumab combined with low-dose PF (cisplatin + 5-fluorouracil) in the neoadjuvant treatment of locally advanced head and neck squamous cell carcinoma

Подробное описание

The investigatorsdesigned a multi-center, single-arm, small sample clinical pilot study. In the clinical trial, patients were given regimes of induction therapy with PLPF (Pembrolizumab + Low dose- P (Platinum) F (5-Fluorouracil)): 6 cycles of Pembrolizumab treatment. Herein, the investigators describe eight consecutive unselected LA SCCHN (Locally Advanced Head and Neck Squamous Cell Carcinoma) patients based on 6 completed cycles of PLPF induction therapy.

Вмешательства

• Комбинированный продукт pembrolizumab+cisplatin + 5-FU
  ivgtt, pembrolizumab 200mg d1+cisplatin20 mg/m2 qd d1-d3 + 5-fluorouracil 3000mg/m2 last for 120hours, six circles. Subjects will undergo surgery after receiving neoadjuvant chemotherapy within 3 weeks, followed by adjuvant therapy and pembrolizumab alone maintenance treatment.

Первичные конечные точки

• Primary site CR rate after neoadjuvant therapy [Срок оценки: Up to 6 months]

Вторичные конечные точки (9)

• Incidence of adverse reactions during neoadjuvant therapy [Срок оценки: up to 2 years]
• The stages of descent after neoadjuvant therapy [Срок оценки: up to 6 months]
• Primary site pCR rate after neoadjuvant therapy [Срок оценки: Up to 6 months]
• EFS [Срок оценки: up to 2 years]
• DFS [Срок оценки: up to 2 years]
• PFS [Срок оценки: up to 2 years]
• OS [Срок оценки: 2 years]
• One year local control rate [Срок оценки: up to 6 months]
• 1-, 2-year survival rates [Срок оценки: up to 2 years]

Критерии участия

Критерии включения

• Age ≥ 18 years old, ≤ 85 years old
• Histologically or cytologically proven squamous cell carcinoma of the head and neck; Patients diagnosed with head and neck squamous cell carcinoma with stage III and IV A without distant metastasis according to AJCC staging (8th editon), including squamous cell carcinoma of oropharyngeal (P16-), oral cavity, hypopharyngeal and larynx
• Measurable primary lesions per RECIST 1.1 criteria
• Treatment-naive patients without any previous disease-related therapy (except for diagnostic biopsies on primary lesions)
• ECOG performance status of 0 or 1
• Selective standard surgery+ standard adjuvant chemo-radiotherapy/radiotherapy as judged by the investigator
• No active autoimmune disease
• No concurrent malignancy
• Life expectancy is estimated to be over 3 months
• Have sufficient tumour tissue samples available for CPS PD-L1 immunohistochemical examination (22C3 DAKO)
• No abvious signs of hematological disorders, ANC≥1.5×109 /L, platelets ≥100×109 /L, Hb≥ 90 g/L,WBC ≥3.0×109 /L before enrollment, no blood transfusion and bleeding tendency within 7 days
• ALT,AST and ALP ≤ 2.5 × upper limit of normal (ULN); Serum bilirubin ≤ 1.5 × ULN, for patients with known Gilbert disease, serum bilirubin ≤ 3 x ULN
• Serum creatinine ≤1.5 or creatinine clearance>50 mL/min
• HPV status determined by p16 IHC, in situ hybridization, or by polymerase chain reaction-based assays
• Able to understand this study, patient and (or) legal representative voluntarily agree to participate in this trial and sign informed consent

Критерии исключения

• Multiple organs failure
• HPV p16 positive oropharyngeal cancer
• Patients with local advanced head and neck squamous cell carcinoma stage T4B and/or N3
• Patients with distant metastasis
• Uncontrolled serious diseases that, as assessed by investigator, may affect the subject's treatment with the study protocol, such as serious heart disease, cerebrovascular disease, uncontrolled diabetes mellitus, uncontrolled hypertension, uncontrolled infection, active peptic ulcer, etc.
• Diagnosis of dementia, altered mental status or any mental illness that would prevent subjects understanding or giving informed consent or completing questionnaires
• Subjects with ≥ Grade 2 peripheral neuropathy according to CTCAE V5.0
• Subjects with ≥ Grade 2 hearing impairment according to CTCAE V5.0
• History of allergy or hypersensitivity to any of the therapeutic ingredients
• Diagnosis of malignancy within 5 years prior to screening, including HNSCC (other than current HNSCC) and other malignancies; Eligibility is achieved if all of the following criteria are met: malignancies received curative therapy, such as adequately treated cervical carcinoma in situ, non-melanoma cutaneum carcinoma, localized prostate cancer after radical operation, breast ductal carcinoma in situ after radical operation; There was also no evidence of recurrence or metastasis based on imaging and tumor markers
• Known history of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
• Patients diagnosed with nasopharyngeal carcinoma or squamous cell carcinoma whose lesions are located in parts other than the oral cavity, oropharynx, larynx and hypopharynx (such as sinuses, paranasal sinuses and unknown primary site)
• Participated in other clinical intervention trials or received other investigational therapies within 30 days prior to screening
• Patients received systemic corticosteroids (prednisone equivalent dose>10mg/day) or other immunosuppressive drugs within 14 days prior to randomization. If there is no active autoimmune disease, inhaled or topical steroid hormones and adrenal hormone replacement therapy with prednisone equivalent doses>10mg per day are permitted
• Pregnant or breastfeeding; Subjects of childbearing age refuse to accept contraceptive measures
• Patients unfit for study as assessed by the investigator
• Received systemic antibiotics within 1 weeks prior to first dose of study therapy or active infection requiring treatment
• Known history of HBV infection (defined as HBsAg positive) or active HCV infection (defined as HCV RNA detected)
• Has received live vaccine during study or within 30 days prior to first dose of study therapy

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 7 центров

• The Affiliated Hospital of Qingdao University — Qingdao
• Zhejiang Provincial People's Hospital — Ханчжоу
• Sir Run Run Shaw Hospital School of Medicine,Zhejiang University — Ханчжоу
• Zhejiang Cancer Hospital — Ханчжоу
• Ningbo Medical Center Lihuili Hospital — Ningbo
• Tianjin Cancer Hospital Airport Hospital — Тяньцзинь
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou

Идентификаторы

NCT: NCT05446467 · KPF20220630

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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