Ablative radiotherapy for metastatic cancer treatment

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

This study is testing if a new type of targeted radiation therapy can help people with multiple metastatic cancers live longer and feel better compared to standard treatment.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 138 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 2 sites (London, Ontario and 1 other locations)
• Trial ID: NCT05508464 on ClinicalTrials.gov

What this trial studies

This international multicentre trial evaluates the effectiveness of stereotactic ablative radiotherapy (SABR) compared to standard care in patients with polymetastatic cancer. Participants will be randomly assigned to receive either SABR or standard treatment, with the aim of assessing overall survival, progression-free survival, quality of life, and treatment toxicity. The trial begins as a phase II study, with the potential to transition to a phase III trial based on initial findings. The study focuses on patients with multiple metastases who can safely receive targeted radiotherapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 or older with histologically confirmed metastatic cancer and at least 11 metastases that can be safely treated.

Not a fit: Patients with fewer than 11 metastases or those whose primary tumor cannot be safely treated will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival and quality of life for patients with metastatic cancer.

How similar studies have performed: Previous studies have shown promising results with SABR in select metastatic patients, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Where this trial is running

London, Ontario and 1 other locations

• London Health Sciences Centre- London Regional Cancer Program — London, Ontario, Canada (RECRUITING)
• University Hospital of Zurich — Zurich, Switzerland (RECRUITING)

Study contacts

• Study coordinator: Timothy Nguyen, M.D.

Conditions: Metastatic Cancer