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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Cancer
• Intervention / Treatment: Other: Standard of Care Treatment; Radiation: Stereotactic Ablative Radiotherapy (SABR)

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Alberta Health Services-Cross Cancer Institute
  • British Columbia
    • Prince George, British Columbia, Canada, V2M 7E9
      • BC Cancer - Prince George
    • Surrey, British Columbia, Canada, V3V 1Z2
      • BC Cancer Fraser Valley Centre
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Agency Branch
    • Victoria, British Columbia, Canada, V8R 4X1
      • BC Cancer - Victoria Centre
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Toronto, Ontario, Canada, M5G1X6
      • Princess Margaret Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care Treatment; 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; May include: Continue with current systemic agent(s); Observation; Switch to next-line treatment Palliative radiotherapy is allowed in this arm.
Experimental: Stereotactic Ablative Radiotherapy (SABR); 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); Patients will receive stereotactic ablative radiotherapy to all sites of progressive disease, with continuation of current systemic agents.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Publications and helpful links

General Publications

• Lee J, Koom WS, Byun HK, Yang G, Kim MS, Park EJ, Ahn JB, Beom SH, Kim HS, Shin SJ, Kim K, Chang JS. Metastasis-Directed Radiotherapy for Oligoprogressive or Oligopersistent Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2022 Jun;21(2):e78-e86. doi: 10.1016/j.clcc.2021.10.009. Epub 2021 Nov 18.
• Schellenberg D, Gabos Z, Duimering A, Debenham B, Fairchild A, Huang F, Rowe LS, Severin D, Giuliani ME, Bezjak A, Lok BH, Raman S, Chung P, Zhao Y, Ho CK, Lock M, Louie AV, Lefresne S, Carolan H, Liu M, Yau V, Ye A, Olson RA, Mou B, Mohamed IG, Petrik DW, Dosani M, Pai H, Valev B, Gaede S, Warner A, Palma DA. Stereotactic Ablative Radiation for Oligoprogressive Cancers: Results of the Randomized Phase 2 STOP Trial. Int J Radiat Oncol Biol Phys. 2025 Jan 1;121(1):28-38. doi: 10.1016/j.ijrobp.2024.08.031. Epub 2024 Aug 19.

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Actual): July 31, 2022
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: April 28, 2016
• First Submitted That Met QC Criteria: April 28, 2016
• First Posted (Estimated): April 29, 2016

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 24, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis
• Other Study ID Numbers: STOP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO