Palliative RadIotherapy of Multiple Metastatic Sites Before First Line of Systemic Therapy With Immune Checkpoint Inhibitors and Chemotherapy in Metastatic Non-Small-Cell Lung Cancer

NCT05440916 | Completed Phase 2

• 1 other identifier: 0120-127/2022/3
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

The study is designed as a non-randomized Phase 2 clinical intervention study. The study will include patients with disseminated Non-Small Cell Lung Carcinoma (NSCLC) which are eligible for first line of systemic treatment with immune checkpoint inhibitors and platinum-based chemotherapy (PDL1 less than 50%). Patients will receive palliative radiotherapy to multiple sites (2 to 5 sites) prior to systemic treatment. Results of treatment will be compared to historical cohort of patients treated only with systemic therapy.

Conditions

Carcinoma, Non-Small-Cell Lung; Metastatic Lung Non-Small Cell Carcinoma; Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Disease status will be evaluated based on imaging results until progression or death; assessed every three months.

  From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months after the completion of study.

Secondary Outcomes (4)

• Overall Survival (OS)

  From the date of randomization until the date of death, or the last follow up date on which the participant was reported alive, assessed up to 18 months.

• Objective Response Rate (ORR)

  Assessment after 3 months after the date of randomization and every 3 months up until progression. Assessed up to 18 months after the completion of study.

• Patterns of progression

  Assessed up to 18 months after the completion of study.

• A review of predictive maker PDL1 - indicating a better response to combination therapy

  From the start of treatment until the date of documented progression or death, whichever comes first, assessed up to 18 months after the completion of study.

Study Arms (2)

Study group

EXPERIMENTAL

Patients with metastatic Non-Small Cell Lung Carcinoma eligible for first line systemic treatment with chemotherapy and immune checkpoint inhibitors (PDL1 less than 50%) Radiotherapy: palliative irradiation of 2 to 5 sites (parenchymal/bone/soft tissue metastasis and/or primary lung tumour) with fractionation: 5 fractions of 4Gy (total dose 20Gy) in one week before systemic therapy.

Radiation: Palliative Radiotherapy: 5 x 4Gy; Drug: chemotherapy + immune checkpoint inhibitors

Historical cohort

OTHER

Patients with metastatic Non-Small Cell Lung Carcinoma treated with first line of systemic therapy with chemotherapy and immune checkpoint inhibitors (PDL1 less than 50%). Radiotherapy: no radiation therapy during the first line of systemic treatment before progression of disease.

Drug: chemotherapy + immune checkpoint inhibitors

Interventions

Palliative Radiotherapy: 5 x 4Gy RADIATION

Palliative irradiation of 2 to 5 sites (metastatic sites or/and primary lung tumour) in one week before systemic therapy. Systemic therapy should be given as soon as possible after irradiation.

Study group

chemotherapy + immune checkpoint inhibitors DRUG

Systemic therapy according to national/European recommendations.

Historical cohort; Study group

Eligibility Criteria

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

You may qualify if:

• Signed consent to the study before the start of the procedures related to the protocol
• Age ≥ 18 years at time of study entry
• ECOG performance status 0-2
• Histologically or cytologically confirmed non-small cell lung cancer, with expression of PD-L1 of less than 50%
• Stage IV metastatic Non-Small Cell Cancer confirmed by CT scan (of brain, chest and abdomen) or PET CT
• Patients must be eligible for first line of systemic treatment with standard of care checkpoint inhibitor immune therapy and chemotherapy - according to the recommendations
• Patients treated with surgery or radiation and chemotherapy for limited non-small cell carcinoma in the past is permitted

You may not qualify if:

• Metastatic non-small cell carcinoma with known oncogenic alterations suitable for targeted treatment
• Brain or meningeal metastases that are not under control
• Other malignancy (other than non-small cell carcinoma) present that has progressed and/or requires active treatment
• Previous malignancy, unless cured or complete remission has been achieved for at least 2 years prior to enrolment and does not require maintenance treatment. With the exception of basal cell carcinoma or squamous cell carcinoma of skin, which was treated and precancerous diseases and in situ cancers
• Patients with interstitial lung disease
• The possibility of radical treatment of oligometastatic disease (primary tumour and metastases)
• Patients who are not eligible for checkpoint immune inhibitor treatment due to contraindications such as autoimmune diseases, with the exception of some exceptions (Vitiligo; type I diabetes; hormone replacement hypothyroidism; psoriasis that does not require systemic treatment or other autoimmune diseases that do not limit checkpoint immune inhibitors treatment)
• Previous treatment with anti PD-1, anti PD-L1, anti CTLA-4 antibodies, or any other treatment that affects T lymphocytes or checkpoint pathways
• Patients with known sensitivity to monoclonal antibodies
• Patients with known HIV infection
• Patients with active or chronic hepatitis B and / or C
• Pregnant and breastfeeding mothers
• Patients with serious and uncontrollable health problems (physical and mental), which, according to researchers, could affect the poor participation of patients and make it difficult to interpret the results
• Patients on corticosteroid therapy (more than 10 mg methylprednisolone or equivalent) prior to enrolment

Sponsors & Collaborators

• University Medical Centre Maribor: lead
• Institute of Oncology Ljubljana: collaborator
• The University Clinic of Pulmonary and Allergic Diseases Golnik: collaborator

Study Sites (3)

University Clinic Golnik

Golnik, 4204, Slovenia

Location

Institute of Oncology Ljubljana

Ljubljana, 1000, Slovenia

Location

University Medical Centre Maribor

Maribor, 2000, Slovenia

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 30, 2022
• First Posted: July 1, 2022
• Study Start: July 14, 2022
• Primary Completion: January 13, 2025
• Study Completion: September 1, 2025
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

SL (3)