Stereotactic Ablative Radiotherapy for Comprehensive Treatment of 4-10 Oligometastatic Tumors

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized Phase III Trial of Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of 4-10 Oligometastatic Tumors (SABR-COMET 10)

Conditions
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Metastatic Tumors

Intervention / Treatment
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* Radiation: Palliative Radiation
* Drug: Chemotherapy
* Drug: Immunotherapy
* Drug: Hormones
* Other: Observation
* Radiation: Stereotactic Ablative Radiotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard arm<br>Standard of care treatment: palliative radiotherapy, chemotherapy, immunotherapy, hormones, or observation, is at the discretion of the treating oncologist. | Radiation: Palliative Radiation<br>* 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.<br>* Other names: Palliative Radiotherapy;Drug: Chemotherapy<br>* Chemotherapy may be given as indicated.<br>Drug: Immunotherapy<br>* Immunotherapy may be given as indicated.<br>Drug: Hormones<br>* Hormones may be given as indicated.<br>Other: Observation<br>* Observation only is acceptable if this is the standard practice.<br>|
| Experimental: Stereotactic Arm<br>Stereotactic ablative radiotherapy, plus standard of care treatment: chemotherapy, immunotherapy, hormones, or observation given at the discretion of the treating oncologist. | Drug: Chemotherapy<br>* Chemotherapy may be given as indicated.<br>Drug: Immunotherapy<br>* Immunotherapy may be given as indicated.<br>Drug: Hormones<br>* Hormones may be given as indicated.<br>Other: Observation<br>* Observation only is acceptable if this is the standard practice.<br>Radiation: Stereotactic Ablative Radiotherapy<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival at Study Completion | Time from randomization to death from any cause. | At approximately end of year 6 (study completion) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Time from randomization to disease progression at any site or death. | At approximately year 3, and end of year 6 (study completion) | 
| Time from randomization to development of new metastatic lesions | New metastatic lesions will be detected using computed tomography, magnetic resonance imaging, and/or bone scans. | At approximately end of year 6 (study completion) | 
| Quality of Life as measured by the Functional Assessment of Cancer Therapy- General (FACT-G) questionnaire |  | At approximately end of year 6 (study completion) | 
| Quality of Life as measured by the EuroQOL Group EQ-5D-5L questionnaire |  | At approximately end of year 6 (study completion) | 
| 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) |