Metastatic Tumors
Conditions
Brief summary
In patients with a limited oligometastatic burden (cancer has spread but is not yet considered metastatic), emerging evidence suggests that treatment of all sites of disease with ablative therapies can improve patient outcomes, including overall- and progression-free survival. The application of Stereotactic Ablative Radiotherapy (SABR) for patients with 4-10 metastatic deposits appears promising, yet it is unclear if all patients with greater than 3 oligometastatic lesions benefit from ablative therapies in terms of improved Overall Survival (OS), Progression Free Survival (PFS), or quality of life. The purpose of this study is to assess the impact of SABR, compared to standard of care treatment, on overall survival, oncologic outcomes, and quality of life in patients with a controlled primary tumor and 4-10 metastatic lesions.
Interventions
RADIATIONPalliative Radiation
Investigators should follow the principles of palliative radiotherapy as per the individual institution in order to alleviate symptoms or prevent complications. If radiotherapy is indicated, recommended doses are 8 Gy in 1 fraction, 20 Gy in 5 fractions, and 30 Gy in 10 fractions.
DRUGChemotherapy
Chemotherapy may be given as indicated.
DRUGImmunotherapy
Immunotherapy may be given as indicated.
DRUGHormones
Hormones may be given as indicated.
OTHERObservation
Observation only is acceptable if this is the standard practice.
RADIATIONStereotactic Ablative Radiotherapy
Total dose of radiation and number of fractions will depend on the site of disease. Doses are 20 Gy in 1 fraction, 30 Gy in 3 fractions (every 2 days), or 35 Gy in 5 fractions (daily).
Sponsors
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
British Columbia Cancer - Centre for the North
Beaston West of Scotland Cancer Centre
London Health Sciences Centre
David Palma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 or older * Willing to provide informed consent * Karnofsky performance score greater than 60 * Life expectancy greater than 6 months * Histologically confirmed malignancy with metastatic disease detected on imaging. Biopsy of metastasis is preferred, but not required. * Controlled primary tumor defined as: at least 3 months since original tumor treated definitively, with no progression at primary site * Total number of metastases 4-10 * All sites of disease can be safely treated based on a pre-plan
Exclusion criteria
* Serious medical comorbidities precluding radiotherapy. These include interstitial lung disease in patients requiring thoracic radiation, Crohn's disease in patients where the GI tract 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 in general is allowed, as long as the composite plan meets dose constraints herein. For patients treated with radiation previously, biological effective dose calculations should be used to equate previous doses to the tolerance doses listed below. All such cases must be discussed with one of the study PIs. * Malignant pleural effusion * Inability to treat all sites of disease * Any single metastasis greater than 5 cm in size. * Any brain metastasis greater than 3 cm in size or a total volume of brain metastases greater than 30 cc. * Metastasis in the brainstem * Clinical or radiologic evidence of spinal cord compression * Dominant brain metastasis requiring surgical decompression * Metastatic disease that invades any of the following: GI tract (including esophagus, stomach, small or large bowel), mesenteric lymph nodes, or skin * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival at Study Completion | At approximately end of year 6 (study completion) | Time from randomization to death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time from randomization to development of new metastatic lesions | At approximately end of year 6 (study completion) | New metastatic lesions will be detected using computed tomography, magnetic resonance imaging, and/or bone scans. |
| Quality of Life as measured by the Functional Assessment of Cancer Therapy- General (FACT-G) questionnaire | At approximately end of year 6 (study completion) | — |
| Progression-free Survival | At approximately year 3, and end of year 6 (study completion) | Time from randomization to disease progression at any site or death. |
| Toxicity as measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 | End of years 1, 2, 3, 4, 5, and 6 (study completion) | — |
| Overall Survival at midpoint of Study | At approximately year 3 (midpoint) | — |
| Quality of Life as measured by the EuroQOL Group EQ-5D-5L questionnaire | At approximately end of year 6 (study completion) | — |
Countries
Australia, Canada, Netherlands, Switzerland, United Kingdom
Outcome results
None listed