Stereotactic Ablative Radiotherapy for Oligo-Progressive Non Small Cell Lung Cancer

Study Overview
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Brief Summary
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A registry-based randomized screening phase II trial. A total of 68 patients with metastatic non small cell lung cancer on systemic therapy with oligoprogression to 1-5 extracranial lesions will be randomized using a 1:1 ratio to standard of care (begin next-line systemic therapy, best supportive care, continue current systemic line, based on treating physician decision) vs. receive stereotactic ablative radiotherapy to all oligoprogressive lesions while continuing their current systemic therapy.

Official Title
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Stereotactic Ablative Radiotherapy for Oligo-Progressive Disease REfractory to Systemic Therapy in Non Small Cell Lung Cancer: A Registry-based Phase II Randomized Trial

Conditions
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Lung Cancer Metastatic

Intervention / Treatment
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* Radiation: SABR
* Other: Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Metastatic NSCLC enrolled in our CRCHUM Lung Cancer Registry and co-enrolled to the PERa registry Ability to provide written informed consent Eastern Cooperative Oncology Group (ECOG) performance status 0-3 Oligoprogression to 1-5 extracranial lesions ≤ 5cm and involving ≤ 3 organs. Progression at the primary tumor site should be counted within the total of 5 lesions. For patients with lymph node metastases, each node is counted as one site of metastasis. Oligoprogression while on ICI or TKI (any line) Patients with brain metastasis are allowed; brain metastasis are not counted in the maximum number of lesions and should be treated as per standard of care All sites of disease can, in the opinion of the investigator, be safely treated and targetable with SABR (taking into account prior local therapy, organ function and underlying medical condition such as inflammatory bowel disease, pulmonary fibrosis, etc.) Patients with prior metastases that have been treated with ablative therapies (e.g. radiotherapy, surgery or radiofrequency ablation) before their current line of systemic therapy, are eligible. Exclusion Criteria: Any lesion beyond 5 cm Pregnancy or breastfeeding Any medical condition that could, in the opinion of the investigator, preclude radiotherapy or prevent follow-up after radiotherapy. Presence of spinal cord compression Metastatic disease that invades the GI tract (including esophagus, stomach, small or large bowel)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized screening phase II trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of care<br>Switch to subsequent systemic therapy line, best supportive care or continue current systemic line | Radiation: SABR<br>* SABR to all oligoprogressive lesions + continuation of current systemic therapy<br>|
| Experimental: Experimental SABR arm<br>Definitive SABR to oligoprogressive lesions + continue current systemic therapy | Other: Standard of care<br>* Patients on the standard arm will be treated as per standard of care in our institution. Treatment options could include switching to next systemic therapy line, best supportive care or continuing on current systemic therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | PFS defined from randomization to disease progression at any site or death | 5 years | 
| OS | OS defined as time from randomization to time of death from any cause. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life Measured using the FACT-G tool, lung cancer-related patient reported outcome- CTCAE (PRO-CTCAE) | Measured using the FACT-G tool, lung cancer-related patient reported outcome- CTCAE (PRO-CTCAE) | 5 years | 
| Quality of life 5-level EQ-5D (EQ-5D-5L) | questionnaire | 5 years | 
| Grade ≥ 3 toxicity | Measured using the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 5 years | 
| Local control | Defined as time from the end of SABR treatment to date of local failure and will be measured only in the experimental arm | 5 years | 
| Time to next systemic therapy | Defined as time from randomization to time of subsequent therapy line | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non small cell lung cancer, oligoprogression, steretactic body radiotherapy