Stereotactic ablative radiotherapy versus single‑fraction palliative radiotherapy for oligoprogressive metastatic cancer

Stereotactic Radiotherapy Versus Palliative Conventional Radiotherapy for Oligoprogressive Metastatic Cancers: A Double-Blind Randomized Phase III Trial

This trial will test whether stereotactic ablative radiotherapy (SABR) works better than single‑fraction palliative radiotherapy (8 Gy) for people with 1–5 oligoprogressive metastatic lesions to delay the need for next‑line systemic therapy and improve quality of life.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 194 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: British Columbia Cancer Agency (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Surrey, British Columbia)
• Trial ID: NCT06918951 on ClinicalTrials.gov

What this trial studies

STOP-2 is a phase III, double‑blind, randomized trial enrolling 194 participants with solid tumors and 1–5 oligoprogressive lesions to compare SABR against single‑fraction palliative radiotherapy (8 Gy) delivered to all progressing sites. Participants are randomized 1:1 and treatment assignment is blinded to participants, enrolling oncologists, and the study statistician. Primary outcomes include progression‑free survival on next systemic therapy (PFS‑NEST), oncologic endpoints, quality of life, and feasibility measures such as accrual and success of double‑blinding. Eligibility includes adults with metastatic solid tumors (excluding lymphoma and myeloma), ECOG 0–2, life expectancy ≥6 months, and RECIST‑defined progression in up to five lesions, with treatments and follow‑up at the participating center.

Who should consider this trial

Good fit: Ideal candidates are adults (≥19) with metastatic solid tumors (not lymphoma/myeloma), ECOG 0–2, life expectancy ≥6 months, and 1–5 RECIST‑defined oligoprogressive lesions who can attend the study center and provide informed consent.

Not a fit: Patients with more than five progressing lesions, hematologic cancers such as lymphoma or myeloma, poor performance status (ECOG >2), or life expectancy under six months are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, SABR could extend the time before patients need a change in systemic therapy and help maintain or improve quality of life compared with single‑fraction palliative radiotherapy.

How similar studies have performed: Prior randomized and non‑randomized studies of SABR in oligometastatic settings (for example SABR‑COMET) have shown improvements in progression‑free and in some cases overall survival, but randomized data specifically for oligoprogression remain limited.

Eligibility criteria

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

Where this trial is running

Surrey, British Columbia

• BC Cancer - Surrey — Surrey, British Columbia, Canada (Recruiting)

Study contacts

• Study coordinator: Sarah Baker, MD, PhD, FRCPC

Conditions Oligoprogression; Oligometastatic Disease; OligoProgressive Metastatic Disease; SABR; Radiotherapy; Quality of life; Metastatic Cancer