Radiotherapy Strategies for Use in Combined Treatment of Small-cell Lung Cancer

Официальное название

Assessment of Radiotherapy Strategies for Use in Combined Treatment of Small-cell Lung Cancer at the Stage of Extensive Disease - a Research Experiment

Обзор

The purpose of this study is to evaluate the efficacy of radiotherapy as part of the combined treatment approach for patients diagnosed with histopathologically confirmed small cell lung cancer (SCLC) in the advanced stage of extensive disease (ED) who are undergoing chemo-immunotherapy. The planned study aims to assess the impact of incorporating consolidative radiotherapy into the treatment strategy, focusing on residual changes following chemo-immunotherapy (during immunotherapy) and its effect on progression-free survival. This research experiment will be conducted as a randomized multi-center study, comprising the following treatment arms: * Arm I: Continuation of standard of care - PDL1/PD1 immunotherapy (durvalumab or atezolozumab) after chemo-immunotherapy based on platinum compounds; * Arm II: Standard of care, followed by consolidating radiotherapy of the chest area and possibly metastases (if indicated) in doses and for palliative indications (total dose of 30 Gy in 10 daily doses of 3 Gy each); * Arm III: Standard of care, followed by consolidating radiotherapy in the radical/ablative doses (total dose of 45 Gy delivered in 15 daily fractions of 3 Gy for the chest area, and total dose of 24 Gy in single fractions of 8 Gy administered every 2-3 days for the metastatic lesions) of the chest area and all metastatic lesions. Additionally, as part of routine weekly blood collections, an extra volume of 10 ml of blood will be collected. This additional blood sample will be obtained before starting radiotherapy, during each week of radiotherapy (maximum three collections), and at the time of disease progression (one collection), resulting in a total of five extra samples. The collected blood will be prepared, stored and used for circulating tumor DNA (ctDNA) testing, according to the protocol. The ctDNA analysis data will be utilized as a potential marker to determine the time to progression and assess the benefits derived from the administered radiotherapy.

Вмешательства

• Лучевая терапия Palliative Radiotherapy
  Standard treatment with added consolidative radiotherapy to the chest area and possibly metastatic lesions (if indicated) in doses and for palliative indications (total dose of 30 Gy in 10 daily doses of 3 Gy each).
• Лучевая терапия Radical/Ablative Radiotherapy
  Standard treatment with added radical/ablative radiotherapy (total dose of 45 Gy in 15 daily fractions of 3 Gy to the chest area and total dose of 24 Gy administered in single fractions of 8 Gy every 2-3 days to the metastatic lesions) to the chest area and all metastatic lesions.

Первичные конечные точки

• Progression-free survival (PFS) according to RECIST 1.1 imaging criteria or patient death. [Срок оценки: 12 months after last patient entry]

Вторичные конечные точки (5)

• Overall survival. [Срок оценки: At the end of the study (an average of 1 year after last patient entry).]
• Treatment toxicity (incidence of Grade 3 toxicity according to CTCAE v.5). [Срок оценки: At the end of the study (an average of 1 year after last patient entry).]
• Site of progression (primary lesions [present at baseline]/new lesions). [Срок оценки: At the end of the study (an average of 1 year after last patient entry).]
• Objective response rate (ORR). [Срок оценки: At the end of the study (an average of 1 year after last patient entry).]
• Response rate in nonirradiated lesions. [Срок оценки: At the end of the study (an average of 1 year after last patient entry).]

Критерии участия

Критерии включения

• Histopathological confirmation of small cell lung cancer based on histological or cytological examination.
• Primary clinical stage: Extensive stage of the disease according to VASLG classification or stage IV according to TNM classification.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 prior to randomization.
• Partial response (PR) or stable disease (SD) to platinum-based doublet chemotherapy with durvalumab or atezolizumab based on restaging (positron emission tomography \[PET\]/computed tomography \[CT\] or CT or magnetic resonance imaging \[MRI\]).
• Ability to undergo radiotherapy at a total dose of 45 Gy in 15 daily fractions of 3 Gy to the chest area and a total dose of 24 Gy administered in single fractions every 2-3 days of 8 Gy to the metastatic lesions.
• Clinical control of brain metastases (prior whole-brain irradiation at any stage is acceptable before study entry).
• Measurable residual disease after chemioimmunotherapy (according to RECIST 1.1 solid tumor response assessment criteria) or in case of CR/PR presence of tumor lesions not classified as measurable.
• Volume and number (up to 10) of metastatic lesions allowing for radiotherapy in doses according to the study protocol.
• Absence of clinically significant and uncontrolled co-morbidities with pharmacological treatment.
• Absence of active autoimmune diseases except for diabetes, hypothyroidism, psoriasis, eczema, lichen planus, and vitiligo.
• Adequate hematopoietic function allowing treatment with atezolizumab or durvalumab, according to the current SmPC (Summary of Product Characteristics).
• Renal and hepatic function allowing treatment according to the current SmPC for atezolizumab or durvalumab.

Критерии исключения

• Age under 18 years old.
• Premenopausal women who do not accept the need for effective contraception during radiotherapy and/or chemotherapy/immunotherapy.
• Individuals excluded from participation in a medical experiment based on Article 23A(1) of the Act on the Profession of Physician and Pharmacist.
• Coexistence of other uncontrolled malignant neoplasms.
• Contraindications to the use of atezolizumab or durvalumab as specified in the SmPC.
• Grade 2 or greater CTCAE v.5 pneumonitis secondary to immunotherapy.
• Participation in another clinical trial during the study.
• Prior chest radiotherapy that precludes safe administration of radiotherapy according to the study protocol. Prior palliative radiotherapy to metastatic sites is acceptable before study entry if clinically indicated as determined by the physician.
• Contraindications to radiotherapy according to the approved protocol.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Польша · 2 центра

• Center of Oncology of the Lublin Region St. Jana z Dukli in Lublin — Lublin
• Copernicus Memorial Hospital in Łódź — Lodz

Публикации

• Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A, Bezjak A, Cardenal F, Fournel P, Harden S, Le Pechoux C, McMenemin R, Mohammed N, O'Brien M, Pantarotto J, Surmont V, Van Meerbeeck JP, Woll PJ, Lorigan P, Blackhall F; CONVERT Study Team. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phas PMID 28642008
• Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. doi: 10.1056/NEJMoa1809064. E PMID 30280641
• Slotman BJ, van Tinteren H, Praag JO, Knegjens JL, El Sharouni SY, Hatton M, Keijser A, Faivre-Finn C, Senan S. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet. 2015 Jan 3;385(9962):36-42. doi: 10.1016/S0140-6736(14)61085-0. Epub 2014 Sep 14. PMID 25230595
• Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etopo PMID 33285097
• Gore EM, Hu C, Sun AY, Grimm DF, Ramalingam SS, Dunlap NE, Higgins KA, Werner-Wasik M, Allen AM, Iyengar P, Videtic GMM, Hales RK, McGarry RC, Urbanic JJ, Pu AT, Johnstone CA, Stieber VW, Paulus R, Bradley JD. Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lun PMID 28648948
• Timmerman R. A Story of Hypofractionation and the Table on the Wall. Int J Radiat Oncol Biol Phys. 2022 Jan 1;112(1):4-21. doi: 10.1016/j.ijrobp.2021.09.027. No abstract available. PMID 34919882
• Herbreteau G, Langlais A, Greillier L, Audigier-Valette C, Uwer L, Hureaux J, Moro-Sibilot D, Guisier F, Carmier D, Madelaine J, Otto J, Souquet PJ, Gounant V, Merle P, Molinier O, Renault A, Rabeau A, Morin F, Denis MG, Pujol JL. Circulating Tumor DNA as a Prognostic Determinant in Small Cell Lung Cancer Patients Receiving Atezolizumab. J Clin Med. 2020 Nov 27;9(12):3861. doi: 10.3390/jcm9123861. PMID 33261056
• Schoenfeld DA. Sample-size formula for the proportional-hazards regression model. Biometrics. 1983 Jun;39(2):499-503. PMID 6354290

Идентификаторы

NCT: NCT06529081 · 2023/ABM/01/00040

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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