Clinical trial NCT06529081: Radiotherapy Strategies for Use in Combined Treatment of Small-cell Lung Cancer
Official title: Assessment of Radiotherapy Strategies for Use in Combined Treatment of Small-cell Lung Cancer at the Stage of Extensive Disease - a Research Experiment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Small Cell Lung Carcinoma
Keywords: Small Cell Lung Carcinoma
Extensive Disease
Chemo-immunotherapy
Radiotherapy
Durvalumab
Atezolizumab
Immunotherapy
Lead sponsor: Copernicus Memorial Hospital
Sponsor class: OTHER
Collaborators: name: Medical Research Agency, Poland
First posted: 2024-07-31
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Progression-free survival (PFS) according to RECIST 1.1 imaging criteria or patient death.
timeFrame: 12 months after last patient entry
Secondary outcomes:
measure: Overall survival.
timeFrame: At the end of the study (an average of 1 year after last patient entry).
measure: Treatment toxicity (incidence of Grade 3 toxicity according to CTCAE v.5).
timeFrame: At the end of the study (an average of 1 year after last patient entry).
measure: Site of progression (primary lesions [present at baseline]/new lesions).
timeFrame: At the end of the study (an average of 1 year after last patient entry).
measure: Objective response rate (ORR).
timeFrame: At the end of the study (an average of 1 year after last patient entry).
measure: Response rate in nonirradiated lesions.
timeFrame: At the end of the study (an average of 1 year after last patient entry).
Other outcomes:
Locations:
city: Łódź
country: Poland
facility: Copernicus Memorial Hospital in Łódź
state: Łódzkie
Study officials:
affiliation: Department of Radiotherapy, Copernicus Memoriał Hospital in Łódź, Poland
name: Łukasz Kuncman, PhD
role: PRINCIPAL_INVESTIGATOR
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