Neoadjuvant PD-1 Inhibitor Combined With Cetuximab and Platinum in Resectable Locally Advanced Hypopharyngeal Carcinoma

Официальное название

Neoadjuvant Therapy With Toripalimab Combined With Cetuximab and Platinum for Resectable Locally Advanced Hypopharyngeal Cancer

Обзор

The purpose of this clinical trial is to evaluate the efficacy and safety of immunotherapy combined with cetuximab and platinum neoadjuvant therapy in patients with resectable locally advanced hypopharyngeal cancer. Participants will receive three cycles of TPC neoadjuvant therapy (toripalimab+ cetuximab + platinum), radical surgery (laryngeal preservation surgery if possible), and sequential (chemo)radiotherapy treatment after surgery. This trial aims to answer the following questions: 1. pCR rate 2. MPR rate, ORR, LPR/DFS/OS rare at 1 and 2 years 3. Safety and quality of life

Подробное описание

The standard treatment for patients with resectable hypopharyngeal carcinoma is surgery plus postoperative adjuvant radiotherapy or chemoradiotherapy. Growing evidence shows that neoadjuvant therapy may significantly increase pCR in locally advanced SCCHN patients, potentially improving patient survival. The development of drugs, immunotherapy, and targeted therapy has been proven to improve the overall survival of patients with SCCHN significantly, and PD-1 inhibitor combined with cetuximab has also shown promising efficacy in R/M SCCHN. This study explores the effectiveness and safety of immunotherapy combined with cetuximab and platinum neoadjuvant therapy in patients with resectable locally advanced hypopharyngeal carcinoma.

Вмешательства

• Препарат three cycles (toripalimab + cetuximab + platinum)
  Cetuximab 250 mg/m2 i.v. qw (first loading dose 400 mg/m2) for nine doses; Toripalimab 240 mg/m2 i.v. d1, q21d, three cycles; Cisplatin 25 mg/m2 i.v. d1-3, q21d, three cycles or Carboplatin AUC 5 i.v. d1, q21d, three cycles (patients with cisplatin contraindications or renal impairment after cisplatin use).
• Процедура Radical surgery
  The attending physician should select the appropriate surgical treatment and try to perform radical laryngeal preservation surgery for patients with tumor retraction after induction therapy. Patients who cannot preserve laryngeal function due to tumor load need to undergo total laryngeal resection. According to the scope of pharyngectomy, the surgical treatments include partial laryngopharyngectomy, total laryngectomy and partial pharyngectomy, total laryngopharyngectomy, and total pharyngo-lary
• Лучевая терапия Radiotherapy or chemoradiotherapy
  1. Using intensity-modulated radiotherapy (IMRT) technology, the dose of radiotherapy is determined according to whether there are adverse prognostic factors in the postoperative pathology, including positive margins, extracapsular invasion of lymph nodes, primary pT3 or T4, N2 lymph node lesions, peripheral nerve invasion, vascular/lymphatic infiltration. Primary site: residual GTV or tumor bed dose 60-70Gy: 1.8-2.12 Gy / fraction. Cervical lymph nodes or lymphatic drainage area: 56-70 Gy:

Первичные конечные точки

• Pathological complete response (pCR) rate after neoadjuvant chemotherapy [Срок оценки: Within 3 weeks after surgery]

Вторичные конечные точки (6)

• Major pathologic response (MPR) rate [Срок оценки: Within 3 weeks after surgery]
• Objective response rate (ORR) after neoadjuvant therapy [Срок оценки: Up to 14 weeks after the start of neoadjuvant therapy]
• 1-year and 2-year larynx preservation rate (LPR) [Срок оценки: Two years post-radiotherapy]
• 1-year and 2-year disease-free survival (DFS) rate [Срок оценки: Two years post-radiotherapy]
• 1-year and 2-year overall survival (OS) rate [Срок оценки: Two years post-radiotherapy]
• Adverse Effect [Срок оценки: One year post-radiotherapy]

Критерии участия

Критерии включения

• Pathologically confirmed as hypopharyngeal squamous cell carcinoma;
• Age between 18-75 years;
• Patients with resectable locally advanced hypopharyngeal cancer with T3-4aN0-3bM0 (AJCC 8th) require total laryngectomy;
• Have at least one evaluable target lesion according to RECIST 1.1 criteria.
• No previous treatment for hypopharyngeal carcinoma;
• Satisfactory performance status: ECOG (Eastern Cooperative Oncology Group) scale 0-1;
• Estimated survival ≥ 6 months;
• Normal organ function;
• HBV DNA < 500 IU/mL (or 2500 copies/mL) and HCV RNA negative;
• Signed informed consent;
• Patients who are compliant, willing, and able to follow visiting schedules, treatment plans, laboratory tests, and other research procedures.
• Male and no pregnant female; able to use the contraceptive method during treatment.

Критерии исключения

• Have a history of other cancers in the past five years, except for the following cancers that are cured in the past five years: basal cell carcinoma and squamous cell carcinoma of the skin, early prostate cancer, papillary thyroid cancer, breast ductal carcinoma in situ and cervix carcinoma in situ;
• The target lesion has been treated with radiation therapy or surgery, except for biopsy to confirm the diagnosis of hypopharyngeal carcinoma;
• Previous chemotherapy, immunotherapy, or bio-targeted therapy for the primary tumor;
• Patients who have participated in other clinical trials within four weeks before the trial;
• Any of the following diseases within six months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
• Those with hypertension who cannot be reduced to normal range by antihypertensive drugs (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg).
• Patients with grade I or above coronary heart disease, arrhythmia (including QTc interval prolongation > 450 ms for men and > 470 ms for women), and cardiac insufficiency.
• Patients with positive urine protein (urine protein test 2 + or above, or 24-hour urine protein quantification >1.0g).
• Patients with severe allergic history or allergic constitution; an active autoimmune disease that may worsen when receiving immunostimulants. Patients with type I diabetes, vitiligo, psoriasis, or diseases of hypothyroidism or hyperthyroidism that do not require immunosuppressive therapy are eligible to participate in the study.
• Subjects requiring systemic therapy with corticosteroids (> 10 mg prednisone or equivalent) or other immunosuppressants within two weeks before the first use of the study drug.
• Previously diagnosed immunodeficiency or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) - related disease. hepatitis B virus (HBV) surface antigen positive and HBV-DNA ≥ 500 IU/mL (or 2500 copies/mL), or HCV RNA positive. History of active or previous tuberculosis (TB).
• Patients with a history of psychotropic substance abuse who cannot quit or have mental disorders.
• Vaccination within four weeks before enrollment, except for inactivated vaccine.
• Pregnant or lactating women, those who are in the reproductive period and do not use effective contraception;
• Those whom the investigator deems unsuitable to participate in this trial, such as severe acute or chronic medical conditions (including immune colitis, inflammatory bowel disease, non-infectious pneumonia, pulmonary fibrosis) or psychiatric illness (including recent or active suicidal ideation or behavior) or abnormal laboratory tests.

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 · 1 центр

• Eye & ENT Hospital of Fudan University — Шанхай

Идентификаторы

NCT: NCT06151743 · TPC-SCCHN

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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