Chemotherapy Plus Immunotherapy Combined With SBRT as Neoadjuvant Therapy for Patients With Resectable NSCLC

Официальное название

A Prospective Cohort Study of Chemotherapy Plus Immunotherapy Combined With Stereotactic Body Radiotherapy as Neoadjuvant Therapy for Patients With Resectable Non-small Cell Lung Cancer

Обзор

In this study, patients with EGFR/ALK wild-type, resectable locally advanced NSCLC are expected to receive 1 cycle of chemoimmunotherapy as neoadjuvant therapy, followed by SBRT to the primary lung lesion, and chemoimmunotherapy for 2 cycles. Surgical treatment will be given within 4-6 weeks after the last cycle of chemoimmunotherapy, then immunotherapy maintenance for 1 year.

Вмешательства

• Препарат Chemotherapy
  Patients with squamous cell carcinoma can choose paclitaxel + cisplatin/carboplatin and patients with nonsquamous cell carcinoma can choose pemetrexed + cisplatin/carboplatin. The chemotherapy treatment lasts 3 cycles.
• Препарат Immunotherapy
  Investigators choose PD-1 or PD-L1 according to drug indication and the immunotherapy lasts 3 cycles preoperatively and 1 year after surgery.
• Процедура Radical resection of lung cancer
  Radical resection of lung cancer with lymph node dissection
• Лучевая терапия SBRT
  SBRT for primary lung lesion 8Gy\*3F after first cycle of chemoimmunotherapy

Первичные конечные точки

• Pathological complete response (pCR) [Срок оценки: Assessed up to 24 weeks]

Вторичные конечные точки (4)

• Major pathologic response (MPR) [Срок оценки: Assessed up to 24 weeks]
• 1-year event-free survival (1 year EFS) [Срок оценки: Assessed up to 100 months]
• The R0 resection rate [Срок оценки: Assessed up to 24 weeks]
• Incidence of treatment-related adverse events [Срок оценки: assessed up to 100 months]

Критерии участия

Критерии включения

• Histologically or pathologically confirmed, newly diagnosed non-small cell lung cancer patients;
• Age ≥18 years;
• (Eastern Cooperative Oncology Group, ECOG) (Performance Status, PS) score 0-1;
• According to the 8th-9th edition of (American Joint Committee on Cancer, AJCC) (stage II-IIIA, for stage IIIB included T3-4N2, T4 only included tumor > 7cm);
• Puncture or biopsy samples were tested EGFR/ALK negative;
• Surgically or potentially resectable after discussion by multidisciplinary team (MDT);
• Who has not received systemic antitumor therapy and has not received chest radiotherapy;
• Evaluable lesions in the lung or mediastinum;
• The organ function level should meet the following criteria one week before enrollment: 1) Bone marrow function: hemoglobin ≥80g/L, white blood cell count ≥4.0\*10\^9/L or neutrophil count ≥1.5\*10\^9/L, platelet count ≥100\*10\^9/L; 2) Liver: total serum bilirubin level ≤1.5 times the normal upper limit, when serum total bilirubin level > 1.5 times the normal upper limit, direct bilirubin level ≤ normal upper limit, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the normal upper limit; 3) Kidney: blood creatinine level < 1.5 times the normal upper limit or creatinine clearance ≥50ml/min, urea nitrogen ≤200mg/L; Serum albumin ≥30g/L;
• Male/female of childbearing age agrees to use contraception during the trial period (surgical ligation or oral contraceptives/IUDs + condom contraception);
• Sign informed consent.

Критерии исключения

• Patients with severe dysfunctions of the heart, lungs and other organs who are not suitable for surgery;
• Patients with severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granuloma), etc;
• Other malignancies within 5 years (excluding non-melanoma skin cancer and cervical cancer);
• Patient with active infection, heart failure, heart attack, unstable angina pectoris or unstable arrhythmia within the last 6 months;
• Congenital or acquired immunodeficiency disorders include human immunodeficiency virus (HIV) or a history of organ transplantation or allogeneic stem cell transplantation;
• Patients treated with other immunological agents, chemotherapy agents, other drugs in clinical trials and long-term cortisol therapy were excluded;
• Patients who are allergic or contraindicated to PD-1 inhibitors.

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

• Department of Thoracic Oncology, Hangzhou Cancer Hospital — Ханчжоу

Публикации

• Zhang JT, Liu SY, Gao W, Liu SM, Yan HH, Ji L, Chen Y, Gong Y, Lu HL, Lin JT, Yin K, Jiang BY, Nie Q, Liao RQ, Dong S, Guan Y, Dai P, Zhang XC, Yang JJ, Tu HY, Xia X, Yi X, Zhou Q, Zhong WZ, Yang XN, Wu YL. Longitudinal Undetectable Molecular Residual Disease Defines Potentially Cured Population in Localized Non-Small Cell Lung Cancer. Cancer Discov. 2022 Jul 6;12(7):1690-1701. doi: 10.1158/2159-8 PMID 35543554
• Xia L, Mei J, Kang R, Deng S, Chen Y, Yang Y, Feng G, Deng Y, Gan F, Lin Y, Pu Q, Ma L, Lin F, Yuan Y, Hu Y, Guo C, Liao H, Liu C, Zhu Y, Wang W, Liu Z, Xu Y, Li K, Li C, Li Q, He J, Chen W, Zhang X, Kou Y, Wang Y, Wu Z, Che G, Chen L, Liu L. Perioperative ctDNA-Based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1). Clin Cancer PMID 34844976
• Qiu B, Guo W, Zhang F, Lv F, Ji Y, Peng Y, Chen X, Bao H, Xu Y, Shao Y, Tan F, Xue Q, Gao S, He J. Dynamic recurrence risk and adjuvant chemotherapy benefit prediction by ctDNA in resected NSCLC. Nat Commun. 2021 Nov 19;12(1):6770. doi: 10.1038/s41467-021-27022-z. PMID 34799585
• Galluzzi L, Aryankalayil MJ, Coleman CN, Formenti SC. Emerging evidence for adapting radiotherapy to immunotherapy. Nat Rev Clin Oncol. 2023 Aug;20(8):543-557. doi: 10.1038/s41571-023-00782-x. Epub 2023 Jun 6. PMID 37280366
• Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, Chen KN, Dooms C, Majem M, Eigendorff E, Martinengo GL, Bylicki O, Rodriguez-Abreu D, Chaft JE, Novello S, Yang J, Keller SM, Samkari A, Spicer JD; KEYNOTE-671 Investigators. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Aug 10;389(6):491-503. doi: 10.1056/NEJMoa2302983. Epub 2023 Jun 3. PMID 37272513

Идентификаторы

NCT: NCT06718309 · HZCH-2024-003

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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