RecruitingPhase 3NCT05717166

A Randomized Phase III Trial of Stereotactic Ablative Radiotherapy for Patients With Up to 10 Oligometastases and a Synchronous Primary Tumor.


Sponsor

David Palma

Enrollment

180 participants

Start Date

Oct 6, 2023

Study Type

INTERVENTIONAL

Conditions

Summary

This study is a phase III multi-institutional randomized trial. Patients will be randomized in a 1:2 ratio between current standard of care treatment (Arm 1) vs. standard of care treatment + SABR (Arm 2) to sites of known disease. Patients will be stratified by two of the strongest prognostic factors, based on a large multi-institutional analysis3: histology (Group 1: hormone-sensitive prostate cancer, breast, or renal; Group 2: all others), and number of metastases (Group 1: 1-3; Group 2: 4-10).


Eligibility

Min Age: 18 Years

Inclusion Criteria9

  • Age 18 years or older
  • Willing to provide informed consent
  • Karnofsky performance status \> 60
  • Life expectancy \> 6 months
  • Histologically confirmed malignancy with metastatic disease detected on imaging. Biopsy of metastasis is preferred, but not required.
  • Total number of metastases 1-10 at the time of enrollment, with a primary tumor also present
  • Restaging completed within 12 weeks prior to randomization (see section 5.1)
  • For patients receiving thoracic radiotherapy, the enrolling physician must confirm there are no computed tomography (CT) changes suggestive of fibrotic interstitial lung disease (ILD) (i.e. reticular changes, traction bronchiectasis, or honeycombing) reported on any prior CT scans. If any are present, the patient must be assessed by a respirologist to rule out ILD prior to enrollment.
  • or fewer lifetime metastases from the cancer for which participants are being enrolled

Exclusion Criteria10

  • Serious medical comorbidities precluding radiotherapy. These include ILD in patients requiring thoracic radiation, Crohn's disease in patients where the gastrointestinal (GI) tract will receive radiotherapy, or 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); please see the Child-Pugh score calculator.
  • 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 in Appendix 1. All such cases must be discussed with a member of the study steering committee.
  • Malignant pleural effusion
  • Inability to treat all sites of disease
  • Brain metastasis \> 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
  • Metastatic disease that invades any of the following: GI tract (including esophagus, stomach, small or large bowel), or skin
  • Pregnant or lactating women

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Interventions

RADIATIONPalliative Radiotherapy

Radiotherapy for patients in the standard arm should follow the principles of palliative radiotherapy as per the individual institution, with the goal of alleviating symptoms or preventing imminent complications. Recommended dose fractionations in this arm will include 8 Gy in 1 fraction, 20 Gy in 5 fractions, and 30 Gy in 10 fractions.

DRUGChemotherapy

Pre-specified based on the standard of care approach for that patient.

DRUGHormone therapy

Pre-specified based on the standard of care approach for that patient.

DRUGImmunotherapy

Pre-specified based on the standard of care approach for that patient.

DRUGTargeted Systemic Therapy

Pre-specified based on the standard of care approach for that patient.

OTHERObservation

Pre-specified based on the standard of care approach for that patient.

RADIATIONStereotactic Ablative Radiotherapy

The primary tumor may be treated with SABR or with other local modalities at the discretion of the treating team and/or the local multidisciplinary tumor board. Preferred doses are 20 Gy in 1 fraction, 30 Gy in 3 fractions (every second day), and 35 Gy in 5 fractions (daily).

PROCEDURESurgery

Treatment to the primary tumor and metastases, with SABR preferred, but other options all allowable if those are deemed to be preferable by the treating oncologists. The primary tumor may be treated with SABR or with other local modalities at the discretion of the treating team and/or the local multidisciplinary tumor board. Because of the convenience in using SABR for all lesions, non-SABR modalities should only be used if they are likely to provide a benefit over SABR.

OTHERRadiofrequency Therapy (RFA)

Treatment to the primary tumor and metastases, with SABR preferred, but other options all allowable if those are deemed to be preferable by the treating oncologists.

RADIATIONFractionated Radiation

Treatment to the primary tumor and metastases, with SABR preferred, but other options all allowable if those are deemed to be preferable by the treating oncologists. Tumors in the esophagus, stomach, small intestine or colon should be treated with either fractionated radiation or a lower SABR dose (e.g. 25 Gy in 5 fractions) to minimize the risk of perforation.


Locations(5)

BC Cancer - Centre for the North

Prince George, British Columbia, Canada

BC Cancer - Vancouver

Vancouver, British Columbia, Canada

London Regional Cancer Program of the Lawson Health Research Institute

London, Ontario, Canada

Centre Hospitalier de l'Université de Montréal-CHUM

Montreal, Quebec, Canada

Universitätsspital Zürich

Zurich, Switzerland

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NCT05717166


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