Neoadjuvant Immunochemotherapy in PD-L1-negative LACC

Официальное название

Neoadjuvant Chemotherapy Plus Camrelizumab in PD-L1-negative Locally Advanced Cervical Cancer: a Multicentre, Single-arm, Phase 2 Trial

Обзор

This is a multicenter, prospective, single-arm, phase 2 clinical trial designed to evaluate the therapeutic efficacy of the NACI (neoadjuvant chemotherapy plus Camrelizumab) for PD-L1-negative locally advanced cervical cancer.

Подробное описание

This multicenter, prospective, single-arm clinical trial is designed to enroll patients with PD-L1-negative, locally advanced cervical cancer. Patients will receive an initial course of priming neoadjuvant chemotherapy, followed by two courses of neoadjuvant immunochemotherapy. The study aims to evaluate the effects of combining neoadjuvant chemotherapy with a PD-1 inhibitor on tumor remission rates, surgical complications, positive margin rates, and patient survival. Additionally, the trial will investigate changes in local immune-related factors and tumor cells during treatment, as well as identify biomarkers that may influence the efficacy of neoadjuvant immunochemotherapy.

Вмешательства

• Препарат Camrelizumab
  200 mg, intravenously, 20-60 min. 2 times, every 21 days
• Препарат Paclitaxel-albumin
  260 mg/m² over 30 min, 3 times, every 21 days
• Препарат Cisplatin
  4 h, 75-80 mg/m², 3 times, every 21 days
• Процедура radical surgery
  Radical hysterectomy + pelvic lymphadenectomy 士 para-aortic lymphadenectomy

Первичные конечные точки

• Pathologic complete response [Срок оценки: undergoing surgery; up to 2 years.]

Вторичные конечные точки (7)

• Surgical Complications [Срок оценки: during and after surgery; an average of 3 years.]
• Objective response rate [Срок оценки: measured 3 weeks after the last dose of neoadjuvant treatment and before surgery; up to 2 years.]
• Positive surgical margin rate [Срок оценки: undergoing surgery; 2 years]
• event-free survival [Срок оценки: 7 years]
• overall survival [Срок оценки: 7 years]
• adverse event [Срок оценки: 7 years]
• Patient Reported Outcomes [Срок оценки: 7 years]

Критерии участия

Критерии включения

• FIGO 2018 stage IB3, IIA2, or IIB/IIIC1r (tumor size>4cm) cervical cancer and without any treatment (After undergoing gynecological examinations by two associate chief physicians or above, the staging of the patients was determined);
• Has at least one measurable lesion based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. In principle, the size of the lesion as shown by the magnetic resonance imaging examination is used as the criterion.
• Histologically confirmed squamous carcinoma, adenocarcinoma (common type) or adenosquamous carcinoma of the cervix;
• Negative PD-L1 expression on preoperative pathological examination (Combined positive score < 1);
• 18-70 years of age;
• Eastern Cooperative Oncology Group score ≤ 1;
• WBC≥3.5\*10\^9/L, NEU≥1.5\*10\^9/L, Platelet≥100×10\^9 /L; AST and ALT ≤1.5 times normal upper limit; Total bilirubin ≤1.5 times the upper limit of normal value; serum creatinine and blood urea nitrogen ≤the upper limit of normal value;
• Well-compliance and willing to keep in touch;
• Willing to participate in this study, sign the informed consent, and comply with the requirements and limitations outlined in the Informed Consent Form (ICF) and this form.

Критерии исключения

• Active, known, or suspected autoimmune disease, or a history of an autoimmune disease, except for the following: vitiligo, alopecia areata, Graves's disease, psoriasis, or eczema that has not required systemic therapy within the last 2 years, hypothyroidism that is asymptomatic or requires only stable doses of hormone replacement therapy (due to autoimmune thyroiditis), type 1 diabetes that requires only stable doses of insulin replacement therapy, asthma that subsides completely in childhood and does not require intervention in adulthood, or diseases that do not recur in the absence of external triggers;
• Prior treatment with immune checkpoint inhibitors, including, but not limited to, other anti-PD-1, anti-PD-L1 antibodies, CTLA-4 antibodies, or antibodies against immune co-stimulators (e.g., antibodies against ICOS, CD40, CD137, GITR, OX40 targets, etc.), or any other therapy targeting a tumor's immune mechanism of action;
• Known hypersensitivity to any component and/or any excipient of the trial prescribed medication;
• Immunosuppressive drugs or systemic corticosteroids for immunosuppression (> mg/day of prednisone or other equivalent) within 2 weeks prior to trial dosing; topical, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids are permitted;
• Received herbs with antitumor effects or drugs with immunomodulatory effects (e.g., thymidine, interferon, interleukin-2) within 2 weeks prior to the trial;
• Active systemic infection requiring systemic treatment;
• Serious infection within 4 weeks prior to the first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia;
• Patients with untreated chronic hepatitis B, or HBV carriers with chronic hepatitis B virus (HBV) DNA greater than 1,000 IU/mL, or patients with active hepatitis C. Inactive HBsAg carriers, patients with hepatitis B who have received treatment and are in stable condition (HBV < 1000 IU/mL), and patients with cured hepatitis C are eligible for enrollment. HCV antibody-positive subjects will be eligible for the study only if they have a negative HCV RNA test;
• Known active tuberculosis (TB), patients with suspected active TB should undergo chest X-ray and sputum examination in conjunction with clinical signs and symptoms for exclusion;
• Immunodeficiency or human immunodeficiency virus (HIV antibody positive);
• Subjects with active inflammatory bowel disease or a history of such disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea). Subjects who are unable to swallow or who have malabsorption syndrome, uncontrolled nausea, vomiting, diarrhea, or other gastrointestinal disorders that severely interfere with drug intake and absorption;
• Known interstitial lung disease that is symptomatic or may interfere with detection or treatment of immune-associated pneumonia;
• Treatment with a live or attenuated vaccine administered within 4 weeks prior to the first trial dose, inactivated seasonal influenza virus vaccine is permitted;
• Have received a prior allogeneic bone marrow transplant or solid organ transplant;
• History of primary malignant tumor within the last 5 years;
• Have undergone major surgery (e.g., open abdomen, open chest, organ resection, etc.) and severe trauma within 28 days prior to the first dose of the implantable infusion device is permitted;
• With a history of gastrointestinal perforation, gastrointestinal fistula, or female genital fistula;
• Uncontrolled other co-morbidities, symptoms, or medical history, including (i) persons with one of the following cardiovascular diseases or cardiovascular risk factors: myocardial infarction, unstable angina, pulmonary embolism, acute/continuous myocardial ischemia, cerebral vascular accident, transient ischemic attack, or other arterial or venous thrombosis, embolism, or cerebral ischemic event of clinical significance/requiring pharmacologic intervention; and persons who have had, within 6 months, a symptoms of congestive heart failure (New York Heart Association (NYHA) class III and above); (ii) clinically significant bleeding symptoms or a history of significant bleeding characteristics such as gastrointestinal bleeding, gastric ulcer bleeding, or vasculitis within 1 month prior to the first dose; (iii) clinically active hemoptysis, active diverticulitis, abdominal abscesses, and gastrointestinal obstruction; and (iv) uncontrolled pleural effusion, pericardial effusion, or ascites requiring Repeated drainage of ascites; ⑤ Abnormal liver or kidney development or history of surgery;
• Pregnant or breastfeeding female patients; women of childbearing age who refuse to accept contraceptive measures during neoadjuvant immunotherapy;
• Concurrent participation in other interventional clinical trials; participation in observational and non-interventional clinical trials is permitted;
• Any condition that, in the judgment of the investigator, may result in risk in the receipt of the study drug or that would interfere with the evaluation of the safety of the study drug or the interpretation of the study results. Patients who, in the judgment of the Investigator, are unlikely to comply with the study steps, restrictions, and requirements are not permitted to participate in this study.

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 · 12 центров

• Anhui Provincial Cancer Hospital — Хэфэй
• Beiing Friendship Hospital, Capital Medical University — Пекин
• The First Affiliated Hospital (Southwest Hospital), Army Medical University (Third Militar — Чунцин
• Gansu Provincial Maternity and Child-care Hospital — Lanzhou
• The Affiliated Tumor Hospital of Guangxi Medical University — Nanning
• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Ухань
• Xiangya Hospital, Central South University — Чанша
• Shengjing Hospital of China Medical University — Шэньян
• … и ещё 4 центра

Идентификаторы

NCT: NCT06288360 · NACI-CERV-002 · MA-CervC-II-007 · [2024](S019)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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