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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)

Primary Purpose

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

Status
Recruiting
Phase
Phase 2
Locations
Slovenia
Study Type
Interventional
Intervention
Palliative Radiotherapy: 5 x 4Gy
chemotherapy + immune checkpoint inhibitors
Sponsored by
University Medical Centre Maribor
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University Clinic GolnikRecruiting
  • Institute of Oncology LjubljanaRecruiting
  • University Medical Centre MariborRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Study group

Historical cohort

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS)
Disease status will be evaluated based on imaging results until progression or death; assessed every three months.

Secondary Outcome Measures

Overall Survival (OS)
Amount of time from treatment until death, reported via follow up visit or phone call.
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.
Patterns of progression
Percentage of patients with recorded first site of progression of disease at irradiated sites and non-irradiated sites or both.
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.

Full Information

First Posted
May 30, 2022
Last Updated
September 18, 2022
Sponsor
University Medical Centre Maribor
Collaborators
Institute of Oncology Ljubljana, The University Clinic of Pulmonary and Allergic Diseases Golnik
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1. Study Identification

Unique Protocol Identification Number
NCT05440916
Brief 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
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 14, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Centre Maribor
Collaborators
Institute of Oncology Ljubljana, The University Clinic of Pulmonary and Allergic Diseases Golnik

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed 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%).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non-Small-Cell Lung, Metastatic Lung Non-Small Cell Carcinoma, Non Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Study group
Arm Type
Experimental
Arm Description
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.
Arm Title
Historical cohort
Arm Type
Other
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Palliative Radiotherapy: 5 x 4Gy
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
chemotherapy + immune checkpoint inhibitors
Intervention Description
Systemic therapy according to national/European recommendations.
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
Disease status will be evaluated based on imaging results until progression or death; assessed every three months.
Time Frame
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 Outcome Measure Information:
Title
Overall Survival (OS)
Description
Amount of time from treatment until death, reported via follow up visit or phone call.
Time Frame
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.
Title
Objective Response Rate (ORR)
Description
Using assessment according to RECIST (after 3 months and time to ORR). Percentage of patients with a complete response or partial response.
Time Frame
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.
Title
Patterns of progression
Description
Percentage of patients with recorded first site of progression of disease at irradiated sites and non-irradiated sites or both.
Time Frame
Assessed up to 18 months after the completion of study.
Title
A review of predictive maker PDL1 - indicating a better response to combination therapy
Description
- Percentage of PDL 1 expression on tumour cells, where PFS was significantly better in combination therapy.
Time Frame
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tanja Žnidarič
Phone
+386(0)23211917
Email
tanja.znidaric@gmail.com
Facility Information:
Facility Name
University Clinic Golnik
City
Golnik
ZIP/Postal Code
4204
Country
Slovenia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tanja Žnidarič
Email
tanja.znidaric@ukc-mb.si
Facility Name
Institute of Oncology Ljubljana
City
Ljubljana
ZIP/Postal Code
1000
Country
Slovenia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jasna But
Email
jbut@onko-i.si
Facility Name
University Medical Centre Maribor
City
Maribor
ZIP/Postal Code
2000
Country
Slovenia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tanja Žnidarič
Email
tanja.znidaric@ukc-mb.si

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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