A Study Evaluating Concurrent Chemoradiotherapy Combined With Dual Immune Checkpoint Blockade for Limited-stage Small Cell Lung Cancer

Официальное название

A Phase II Study Evaluating Concurrent Chemoradiotherapy Combined With Dual Immune Checkpoint Blockade (PD-1/CTLA-4) for Limited-stage Small Cell Lung Cancer

Обзор

This study will enroll patients with limited-stage small cell lung cancer (SCLC). Patients will receive chemotherapy (etoposide and platinum-based drugs) combined with dual immune checkpoint blockade (PD-1/CTLA-4) and thymosin alpha 1, with a total cycles of 4. Thoracic radiotherapy was performed no later than the three cycle of chemotherapy. Prophylactic cranial irradiation was recommended for patients who received complete response or partial response after chemoradiotherapy. Finally consolidation therapy with dual immune checkpoint blockade (PD-1/CTLA-4) and thymosin alpha 1 was conducted for one year. The study aims to evaluate the efficacy and safety of this treatment regimen.

Вмешательства

• Препарат Immuno-chemotherapy
  Immuno-chemotherapy regimen included etoposide, cisplatin, iparomlimab and tuvonralimab, and thymosin alpha 1.
• Лучевая терапия Radiotherapy
  Definitive dose of thoracic radiotherapy was delivered no later than the three cycle of immuno-chemotherapy. Prophylactic cranial irradiation (PCI) was delivered with a total dose of 25Gy in 10 fractions. PCI was recommended for patients who achieved complete response or partial response after thoracic chemoradiotherapy.
• Препарат Consolidative therapy
  Consolidation therapy regimen included iparomlimab and tuvonralimab, and thymosin alpha 1, with a duration of one year.

Первичные конечные точки

• Progression-free survival [Срок оценки: 2-year]

Вторичные конечные точки (2)

• Overall survival [Срок оценки: 2-year]
• Treatment-related toxicity [Срок оценки: through study completion, an average of 18 months]

Критерии участия

Критерии включения

• Males or females aged 18 to 75 years or older;
• Patients must have histologically or cytologically confirmed small cell lung cancer (SCLC);
• Stage II-III according to AJCC 8th staging system;
• No prior chemotherapy, radiotherapy, surgery, targeted therapy, or immunotherapy;
• Expected survival ≥ 12 weeks;
• WHO Performance Status (PS) score of 0 or 1;
• Female subjects must not be breastfeeding;
• Women of childbearing potential (WOCBP) must agree to use contraception during the study treatment and for 5 months after the last dose of study drug (i.e., 30 days \[one ovulation cycle\] plus approximately five half-lives of the study drug);
• Adequate organ and bone marrow function as defined by the following criteria:
• Forced Expiratory Volume in 1 second (FEV1) ≥ 800 mL;
• Absolute neutrophil count ≥ 1.5 × 10⁹/L;
• Platelets ≥ 100 × 10⁹/L;
• Hemoglobin ≥ 9.0 g/dL;
• Creatinine clearance ≥ 50 mL/min as calculated by the Cockcroft-Gault formula (Cockcroft and Gault, 1976);
• Serum bilirubin ≤ 1.5 × upper limit of normal (ULN);
• AST and ALT ≤ 2.5 × ULN.

Критерии исключения

• Concurrent enrolment in another clinical study, unless it is an observational(non-interventional) clinical study;
• Mixed small cell and non-small cell lung cancer histology;
• Prior use of anti-PD-1, anti-PD-L1, or anti-CTLA4 antibodies;
• Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access;
• Active or prior documented autoimmune disease within the past 2 years;
• Active or prior documented inflammatory bowel disease (eg. Crohn's disease, ulcerative colitis);
• History of primary immunodeficiency;
• History of organ transplant that requires therapeutic immunosuppression;
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent;
• Known history of tuberculosis;
• History of another primary malignancy within 5 years prior to starting treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study;
• Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control.

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

• Sun Yat-sen University Cancer Center — Гуанчжоу

Публикации

• Garaci E, Pica F, Serafino A, Balestrieri E, Matteucci C, Moroni G, Sorrentino R, Zonfrillo M, Pierimarchi P, Sinibaldi-Vallebona P. Thymosin alpha1 and cancer: action on immune effector and tumor target cells. Ann N Y Acad Sci. 2012 Oct;1269:26-33. doi: 10.1111/j.1749-6632.2012.06697.x. PMID 23045967
• Malhotra J, Chiappori A, Fujioka N, Hanna NH, Feldman LE, Patel M, Moore D, Chen C, Jabbour SK. Phase I/II trial of plinabulin in combination with nivolumab and ipilimumab in patients with recurrent small cell lung cancer (SCLC): Big ten cancer research consortium (BTCRC-LUN17-127) study. Lung Cancer. 2024 Sep;195:107932. doi: 10.1016/j.lungcan.2024.107932. Epub 2024 Aug 21. PMID 39173229
• Huang Y, Yang Y, Zhao Y, Zhao H, Zhou N, Zhang Y, Chen L, Zhou T, Chen G, Wu T, Lu L, Xue S, Kang X, Zhang L, Fang W. QL1706 (anti-PD-1 IgG4/CTLA-4 antibody) plus chemotherapy with or without bevacizumab in advanced non-small cell lung cancer: a multi-cohort, phase II study. Signal Transduct Target Ther. 2024 Jan 29;9(1):23. doi: 10.1038/s41392-023-01731-x. PMID 38282003
• Cheng W, Kang K, Zhao A, Wu Y. Dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in lung cancer. J Hematol Oncol. 2024 Jul 27;17(1):54. doi: 10.1186/s13045-024-01581-2. PMID 39068460
• Duan H, Shi L, Shao C, Wang Y, Wang Z, Ni Y, Zhao J, Sun J, Tong L, Lei J, Jiang T, Liu Z, Yan X. A multicenter, single-arm, open study of neoadjuvant or conversion atezolizumab in combination with chemotherapy in resectable small cell lung cancer (Cohort Study). Int J Surg. 2023 Sep 1;109(9):2641-2649. doi: 10.1097/JS9.0000000000000501. PMID 37428211
• Cheng Y, Spigel DR, Cho BC, Laktionov KK, Fang J, Chen Y, Zenke Y, Lee KH, Wang Q, Navarro A, Bernabe R, Buchmeier EL, Chang JW, Shiraishi Y, Sezgin Goksu S, Badzio A, Shi A, Daniel DB, Hoa NTT, Zemanova M, Mann H, Gowda H, Jiang H, Senan S; ADRIATIC Investigators. Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer. N Engl J Med. 2024 Oct 10;391(14):1313-1327. doi: 10.1056/ PMID 39268857

Идентификаторы

NCT: NCT07103408 · GASTO-10136

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗