Stereotactic Radiotherapy for Oligo-Progressive Metastatic Cancer (The STOP Trial)

Study Overview
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Brief Summary
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A multicenter randomized phase II trial of stereotactic body radiotherapy for oligo-progressive metastatic cancers. Eligible patients will be randomized in a 1:2 ratio between receiving their standard of care therapy or stereotactic ablative radiotherapy (SABR) to all sites of oligo-progressive lesions.Radiotherapy will be administered as soon as possible following randomization, and subjects will be followed until next disease progression. The primary outcome is progression-free survival (PFS).

Official Title
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Stereotactic Radiotherapy for Oligo-Progressive Metastatic Cancer (The STOP Trial): A Randomized Phase II Trial

Conditions
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Metastatic Cancer

Intervention / Treatment
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* Radiation: Stereotactic Ablative Radiotherapy (SABR)
* Other: Standard of Care Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or older Willing to provide informed consent Histologically confirmed Non-Small Cell Lung Cancer (NSCLC) with metastatic disease detected on imaging. Biopsy of metastasis at some time point prior to enrollment is preferred, but not required. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Life expectancy > 3 months Patient has received treatment with systemic therapy (either cytotoxic or targeted, including maintenance therapies) during the past 6 weeks. This most recent systemic therapy agent must have been delivered for a total of at least 3 months, with an initial partial response (PR), complete response (CR) or stable disease (CR) prior to the development of oligo-progressive lesions. Oligoprogression, defined as Response Evaluation Criteria in Solid Tumors (RECIST)-documented progression in up to 5 individual lesions, with no previous radiation or radiofrequency ablation to those sites. Oligoprogression may be defined as: Progression of an individual metastasis according to RECIST 1.1 criteria Unambiguous development of a new metastatic lesion at least 5mm in size Progressive enlargement of a known metastasis on 2 consecutive imaging studies 2- 3 months apart with a minimum 5mm increase in size from baseline All sites of oligoprogression can be safely treated Maximum 3 progressing metastases in any single organ system (i.e. lung, liver, brain, bone), and the total number of metastases must be 5 or less Note for Patients with Brain Metastases: For patients with brain metastases and oligo-progression elsewhere where stereotactic radiation to the brain is deemed to be warranted, this must be specified prior to randomization. If randomized to Standard Arm, patient would receive stereotactic radiation to brain only. If randomized to Experimental Arm, patient would receive stereotactic radiation to brain and to body lesions Exclusion Criteria: Serious medical comorbidities precluding radiotherapy, such as ataxia-telangiectasia or scleroderma. For patients with oligoprogressive lesions in the lung or thorax, this includes interstitial lung disease Prior radiotherapy to a site requiring treatment Malignant pleural effusion Inability to treat all sites of enlarging, oligoprogressive disease Clinical or radiological evidence of spinal cord compression or tumor within 3mm of spinal cord on MRI Any other condition which in the judgment of the investigator would make the patient inappropriate for entry into this study

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care Treatment<br>Patient treatment may include the following 3 options, at the discretion of the treating physicians: Continue with current systemic agent(s) Observation Switch to next-line treatment | Other: Standard of Care Treatment<br>* May include: Continue with current systemic agent(s) Observation Switch to next-line treatment Palliative radiotherapy is allowed in this arm.<br>|
| Experimental: Stereotactic Ablative Radiotherapy (SABR)<br>SABR is delivered to all sites of progressive disease with continuation of current systemic agents. Further oligo-progressive lesions may be treated with SABR if possible. Upon progression at sites not amenable to SABR, the patient may receive any of the options in Arm 1. | Radiation: Stereotactic Ablative Radiotherapy (SABR)<br>* Patients will receive stereotactic ablative radiotherapy to all sites of progressive disease, with continuation of current systemic agents.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival | Progression-Free Survival is defined as the time from randomization to progression of disease or death from any cause | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival is defined as they time from randomization to death from any cause | 5 years | 
| Quality of Life | Quality of life in domains of physical, social/family, emotional, and functional well-being will be assessed with the Functional Assessment of Cancer Therapy (FACT-G) | 5 years | 
| Toxicity | Toxicity related to radiation treatment will be assessed by the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4 for each organ treated (i.e. liver, lung, bone) | 5 years | 
| Lesional Control Rate | Local control rate of lesions treated with SABR | 5 years | 
| Total Time on Chemotherapy | Duration of systemic therapy treatment | 5 years | 
| Duration of current systemic agent treatment after SABR | Arm 2 only | 5 years | 
| Location of sites of further progression after SABR | Sites of progressive disease after SABR are captured in follow up | 5 years |