STOP-2 is a phase III multi-institutional double-blind randomized trial. 194 participants will be enrolled in this trial. Participants will be randomized in a 1:1 ratio between the Control Arm vs. the Experimental Arm.

Participants, enrolling oncologists, and the statistician will be blinded to trial arm assignment.

In the control arm, radiotherapy will consist of 8 Gy in 1 fraction to all sites of oligoprogression, and the experimental arm will consist of SABR treatment to all sites of oligoprogression.

Primary Objectives

• To assess the impact of SABR, compared to palliative conventional radiotherapy, on Progression-free survival on next line systemic therapy (PFS-NEST), oncologic outcomes, and Quality of Life (QOL) in participants with 1-5 oligoprogressing lesions.
• To assess the feasibility of the clinical trial in terms of accrual and success of double-blinding.

Secondary Objectives

• To evaluate and compare the impact of SABR and palliative radiation therapy on the overall survival (OS), progression free survival (PFS), polymetastatic progression-free survival (PPFS);
• To assess and compare the proportion of participants receiving additional radiation therapy and other metastasis-directed interventions during follow-up between both arms;
• To compare the impact of SABR and palliative radiation therapy on the time to initiation of the next line of systemic therapy;
• To identify and compare the anatomic sites of disease progression between the experimental (SABR) and control (palliative radiation) arms;
• To compare the treatment related toxicity among participants in each arm;
• To evaluate and compare the quality of life among participants in each arm;
• To assess the cost-effectiveness of the experimental arm compared to the control arm.

Inclusion Criteria:

1. Age 19 or older

2. Able to provide informed consent

3. Histologically confirmed solid malignancy (excluding lymphoma or myeloma) with metastatic disease detected on imaging

4. Biopsy of metastasis at some time prior to enrollment is preferred, but not required

5. ECOG performance status 0-2

6. Life expectancy ≥ 6 months

7. Progression meeting RECIST criteria in up to 5 individual lesions. Progression may be defined as:

   1. Progression of an individual metastasis according to RECIST 1.1 criteria (≥ 20% enlargement of the tumour vs. baseline or nadir, taking as reference the smallest diameter seen prior to starting or during systemic therapy, and associated with a 5 mm minimum increase in size) OR
   2. Unambiguous development of a new metastatic lesion at least 5 mm in size OR
   3. Progressive enlargement of a known metastasis on 2 consecutive imaging studies 2-3 months apart with a minimum 5 mm increase in size from baseline.
   4. A progressing primary tumor is eligible as per the criteria above

8. If the participant is on systemic therapy at the time of oligoprogression:

   The 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 (SD) prior to the development of oligoprogressive lesions

9. If the participant is not on systemic therapy at the time of oligoprogression:

   (i.e., "oligorecurrence"(1), however, included as "oligoprogression" for the purpose of this study protocol):

10. There must be PR, CR or SD persisting for at least 3 months prior to the development of oligoprogressive lesions

11. Participants who are not on systemic therapy at the time of oligoprogression must have other site(s) of disease (metastases or primary tumor) that are stable or resolved and have not received definitive treatment (inclusive of surgery, radical doses of radiotherapy including SABR, or ablation) and are not going to receive SABR.

12. All sites of oligoprogression can be safely treated

13. Restaging completed within 12 weeks prior to randomization (see section 5.1)

14. Negative urine pregnancy test for People of Child-Bearing Potential (POCBP) within 4 weeks of radiotherapy start date.

Exclusion Criteria:

1. Serious medical comorbidities precluding radiotherapy. These include ataxia-telangiectasia or scleroderma, Crohn's disease in participants where the gastrointestinal (GI) tract will receive radiotherapy, or ulcerative colitis where the bowel will receive radiotherapy.

   a. For participants with oligoprogressive lesions in the lung or thorax, this includes interstitial lung disease.

2. Substantial overlap with a previously treated radiation volume. Prior radiotherapy in general is allowed, provided that the composite plan meets dose constraints herein. For participants treated with radiation previously, biological effective dose calculations should be used to equate previous doses to the tolerance doses listed in Appendix 1. A tissue recovery factor may be used in these calculations and if so, must be clearly documented, along with elapsed time from previous radiotherapy, and approved by the local principal investigator.

3. Current malignant pleural effusion, malignant ascites, or leptomeningeal disease

4. Inability to treat all sites of oligoprogressive disease

5. Liver metastases requiring placement of fiducial markers for SABR, as this would compromise successful blinding. Liver metastases are eligible if: 1) they are treated at an institution that offers liver SABR without fiducial markers or 2) pre-existing markers such as surgical clips or calcifications would serve as fiducial markers

6. Brain metastasis > 3.5 cm in size or a total volume of brain metastases greater than 30 cc.

7. Clinical or radiologic evidence of spinal cord compression. Participants can be eligible if surgical resection has been performed.

8. Participants with spine instability as judged by a Spinal Instability Neoplastic Score (SINS) of >12.

9. Dominant brain metastasis requiring surgical decompression

10. For participants with liver metastases; moderate/severe liver dysfunction (Child Pugh B or C)

11. Liver metastases located in the "Biliary no fly zone" defined for this trial as common biliary track, cystic duct and distal branches (1 cm) + 5 mm

12. Surgical resection of all oligoprogression metastases (i.e. no lesion available to be treated with SABR)

13. Pregnant or lactating individuals

This is a double-blind trial. Participants, enrolling oncologists, and the statistician will be blinded to trial arm assignment. The Coordinating Centre will not be blinded and will maintain a list of trial arm assignments (unblinding master list, in electronic format and accessible to project managers at the Coordinating Centre). Randomization will occur at the Coordinating Centre, and randomization results will be communicated to the clinical trials unit of the participating centre. The trial arm assignment will not be documented at the participating centre. The trials unit staff at the participating centre will then notify the non-enrolling oncologist of the trial arm assignment.