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

Non Small Cell Lung Cancer Clinical Trial

— PRIMM  

Official title:

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 (PRIMM Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05440916
• Other study ID #: 0120-127/2022/3
• Status: Recruiting
• Phase: Phase 2
• Start date: July 14, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: November 2023
• Source: University Medical Centre Maribor
• Contact: Tanja Žnidaric
• Phone: +386(0)23211917
• Email: tanja.znidaric[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The primary objective is to investigate efficacy of radiation therapy before the first line of systemic therapy with immune checkpoint inhibitors and platinum-based chemotherapy in metastatic NSCLC (PDL1 less than 50%).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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
• inclusion of patients treated for few brain metastases (with surgery or ablative radiosurgery) is permitted (if the disease in the central nervous system is under control)
• Prior surgery (diagnostic and therapeutic) and irradiation (for example: stereotactic irradiation of brain metastases) is permitted, provided that patients have fully recovered from the procedure at least 2 weeks before inclusion in the study
• Patients treated with surgery or radiation and chemotherapy for limited non-small cell carcinoma in the past is permitted

Exclusion Criteria:

• 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
• Irradiation 2 months before inclusion in the study, except for stereotactic irradiation of brain metastases (or radiation and chemotherapy for limited non-small cell carcinoma in the past)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Metastatic Lung Non-Small Cell Carcinoma
• Non Small Cell Lung Cancer

Intervention

Radiation:
• Palliative Radiotherapy: 5 x 4Gy
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.

Drug:
• chemotherapy + immune checkpoint inhibitors
Systemic therapy according to national/European recommendations.

Locations

Country	Name	City	State
Slovenia	University Clinic Golnik	Golnik
Slovenia	Institute of Oncology Ljubljana	Ljubljana
Slovenia	University Medical Centre Maribor	Maribor

Sponsors (3)

Lead Sponsor	Collaborator
University Medical Centre Maribor	Institute of Oncology Ljubljana, The University Clinic of Pulmonary and Allergic Diseases Golnik

Country where clinical trial is conducted

Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	Amount of time from treatment until death, reported via follow up visit or phone call.	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.
Secondary	Objective Response Rate (ORR)	Using assessment according to RECIST (after 3 months and time to ORR). Percentage of patients with a complete response or partial response.	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.
Secondary	Patterns of progression	Percentage of patients with recorded first site of progression of disease at irradiated sites and non-irradiated sites or both.	Assessed up to 18 months after the completion of study.
Secondary	A review of predictive maker PDL1 - indicating a better response to combination therapy	- Percentage of PDL 1 expression on tumour cells, where PFS was significantly better in 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.