Ablative Radiotherapy to Restrain Every Metastasis Safely Treatable (ARREST-2): A Randomized Phase II/III Trial

NCT05508464 | Recruiting DMC

• 2 other identifiers: ARREST2REDA 12529
• Study Type: interventional
• Target: 138
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a phase II/III international multicentre randomized trial. Patients will be randomized in a 1:2 ratio between the standard of care (Arm 1) and SABR (Arm 2) to all sites of disease. The study will start as a phase II trial with an opportunity to convert to a phase III trial. The objective of this trial is to determine the impact of SABR on overall survival, progression-free survival, quality of life, and toxicity in patients with polymetastatic disease.

Conditions

Metastatic Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Defined as the time form randomization to death from any cause.

  Time from randomization to death from any cause, patients followed for 5 years

Secondary Outcomes (4)

• Progression-free survival

  Time from randomization to disease progression at any disease site, or death. Up to 5 years

• Quality of life- An individuals perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns.

  Measured at baseline, then every 3 months from randomization until 2 years, then every 6 months until 5 years.

• Quality of life- An individuals perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns.

  Measured at baseline, then every 3 months from randomization until 2 years, then every 6 months until 5 years.

• Toxicity of Ablative Radiotherapy

  Measured at baseline, on treatment, 6 weeks post treatment, every 3 months from randomization until 2 years, then every 6 months until 5 years.

Study Arms (2)

Standard of Care

ACTIVE COMPARATOR

Standard or care palliative radiotherapy (includes the option for no treatment)

Radiation: Arm 1: Standard of Care

SABR

ACTIVE COMPARATOR

SABR to all tumors 6Gy x 5 over 3 weeks

Radiation: Arm 2: SABR

Interventions

Arm 2: SABR RADIATION

SABR to all tumors 6 Gy x 5 over three weeks

SABR

Arm 1: Standard of Care RADIATION

Standard of care palliative radiotherapy

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 or older
• willing and able to provide informed consent
• ECOG performance status 0-2
• Life expectancy \> or equal to 6 months
• Histologically confirmed malignancy with evidence of metastatic disease on imaging
• All sites of disease can be safely treated on a preliminary radiation plan
• \> or equal to 11 metastases (the primary tumor does not have to be controlled and can be included as a target if it can feasibly and safely be treated with SABR. If the primary tumor is treated, a minimum of 12 targets are required0 at least 11 metastases are required in addition to the primary tumor.)
• Investigations required within 12 weeks of enrollment:
• Brain: MRI is required for all patients with known untreated or previously treated brain metastases. MRI is strongly recommended for all tumor sites with a propensity to develop brian metastases.
• Body: 18-FDG PET/CT imaging is recommended, except for tumors where FDG uptake is not expected (e.g. prostate, renal cell carcinoma). PSMA-PET or choline-PET is recommended for prostate cancer. In situations where a PET scan is unavailable, or for tumors that do not take up radiotracer, a CT neck/chest/abdomen/pelvis and bone scan are required.
• Liver: For patients with liver metastases, a diagnostic or simulation MRI is required to confirm the total number of metastases.
• No plans for systemic therapy (i.e. chemotherapy, targeted agent, immunotherapy) for 3 months from the time of enrolment. Reasons may include: a break from systemic therapy is desired by the patient and medical oncologist, the patient declines next line of systemic therapy, or no further systemic therapy options are available. Exceptions include hormone therapy for breast cancer or prostate cancer, which may be continued.
• SABR or palliative radiotherapy should commence no later than 2 weeks after randomization.
• For patients with brain metastases that are going to be treated regardless of the study arm, there must be additional extracranial disease present that will be treated with SABR on Arm 2 and not treated with SABR on Arm 1.

You may not qualify if:

• Serious medical comorbidities precluding radiotherapy. These include interstitial lung disease in patients requiring thoracic radiation, Chrohn's disease in patients where the GI tract will receive radiotherapy, ulcerative colitis where the bowel will receive radiotherapy and connective tissue disorders such as lupus or scleroderma.
• For patients with liver metastases, moderate/severe liver dysfunction (Child-Pugh B or C)
• Substantial overlap with a previously treated radiation volume. Prior radiotherapy is allowed, as long as the composite plan meets dose constraints herein. For patients treated with radiation previously, biologically effective dose calculations should be used to equate previous doses to the tolerance doses listed in Appendix 1. All such cases must be discussed with the study PI.
• Inability to treat all sites of disease. Any brain metastasis \>3 cm in size or a total volume of brain metastases greater than 30 cc.
• Solitary or dominant brian metastasis requiring surgical decompression.
• Radiologic evidence of spinal cord compression.
• Disseminated disease, including leptomeningeal metastases, peritoneal metastases/carcinomatosis, malignant pleural effusion, and lymphangitis carcinomatosis.
• Pregnant or lactating women.

Sponsors & Collaborators

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

Study Sites (2)

London Health Sciences Centre- London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

RECRUITING

University Hospital of Zurich

Zurich, 8091 zurich, Switzerland

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Timothy Nguyen, M.D.

CONTACT

519-685-8500; Timothy.Nguyen@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2022
• First Posted: August 19, 2022
• Study Start: October 16, 2023
• Primary Completion (Estimated): January 1, 2034
• Study Completion (Estimated): January 1, 2034
• Last Updated: April 23, 2026

Record last verified: 2026-03

Locations

CA (1); CH (1)