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

NCT06529081 | Recruiting

• 1 other identifier: 2023/ABM/01/00040
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Small Cell Lung Carcinoma

Keywords

Small Cell Lung Carcinoma; Extensive Disease; Chemo-immunotherapy; Radiotherapy; Durvalumab; Atezolizumab; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) according to RECIST 1.1 imaging criteria or patient death.

  The assessment of the impact of consolidative (radical/palliative) radiotherapy on residual post-chemoimmunotherapy (during immunotherapy) lesions on progression-free survival (PFS).

  12 months after last patient entry

Secondary Outcomes (5)

• Overall survival.

  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).

  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).

  At the end of the study (an average of 1 year after last patient entry).

• Objective response rate (ORR).

  At the end of the study (an average of 1 year after last patient entry).

• Response rate in nonirradiated lesions.

  At the end of the study (an average of 1 year after last patient entry).

Study Arms (3)

Standard Treatment

NO INTERVENTION

PDL1/PD1 immunotherapy (durvalumab or atezolozumab - according to the SmPC) after chemo-immunotherapy based on platinum compounds.

Standard Treatment with Palliative Radiotherapy

EXPERIMENTAL

Radiation: Palliative Radiotherapy

Standard Treatment with Radical/Ablative Radiotherapy

EXPERIMENTAL

Radiation: Radical/Ablative Radiotherapy

Interventions

Palliative Radiotherapy RADIATION

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).

Standard Treatment with Palliative Radiotherapy

Radical/Ablative Radiotherapy RADIATION

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.

Standard Treatment with Radical/Ablative Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Copernicus Memorial Hospital: lead
• Medical Research Agency, Poland: collaborator

Study Sites (2)

Center of Oncology of the Lublin Region St. Jana z Dukli in Lublin

Lublin, Poland

RECRUITING

Copernicus Memorial Hospital in Łódź

Lodz, Łódź Voivodeship, 93-513, Poland

RECRUITING

Related Publications (9)

• 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, phase 3, randomised, superiority trial. Lancet Oncol. 2017 Aug;18(8):1116-1125. doi: 10.1016/S1470-2045(17)30318-2. Epub 2017 Jun 20.

  PMID: 28642008 BACKGROUND

• 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. Epub 2018 Sep 25.

  PMID: 30280641 BACKGROUND

• 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 BACKGROUND

• 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-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. doi: 10.1016/S1470-2045(20)30539-8. Epub 2020 Dec 4.

  PMID: 33285097 BACKGROUND

• 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 Lung Cancer (ED SCLC): NRG Oncology RTOG 0937. J Thorac Oncol. 2017 Oct;12(10):1561-1570. doi: 10.1016/j.jtho.2017.06.015. Epub 2017 Jun 23.

  PMID: 28648948 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Schoenfeld DA. Sample-size formula for the proportional-hazards regression model. Biometrics. 1983 Jun;39(2):499-503.

  PMID: 6354290 BACKGROUND

• Kuncman L, Fijuth J, Tworek D, Sierko E, Cisek P, Maslowski M, Lisik-Habib M, Orzechowska M, Galwas-Kliber K, Antczak A, Chmielewska I, Ziolkowska B, Kurczewska-Michalak M, Kuznicki W, Jedrzejczak N, Ranoszek K, Bilski M. Radiotherapy(R) Integration(I) Strategy for Small(S)-Cell Lung Cancer in Extensive(E) Stage (RISE) with up to 10 metastases- a study protocol of a randomized phase II trial. BMC Cancer. 2025 Jan 24;25(1):142. doi: 10.1186/s12885-025-13552-y.

  PMID: 39856583 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Łukasz Kuncman, PhD

  Department of Radiotherapy, Copernicus Memoriał Hospital in Łódź, Poland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Łukasz Kuncman, PhD

CONTACT

+4842 689 55 55; lm.kuncman@kopernik.lodz.pl

Jacek Fijuth, Prof

CONTACT

+4842 689 55 51; jacekf@kopernik.lodz.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 26, 2024
• First Posted: July 31, 2024
• Study Start: April 1, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

PL (2)