Study Comparing Stereotactic Body Radiotherapy vs Conventional Palliative Radiotherapy (CRT) for Spinal Metastases

Study Overview
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Brief Summary
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The purpose of this study is to find out if SBRT is better than CRT at controlling pain in the spine 3 months after receiving treatment.

Detailed Description
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This research is being done because while there is some evidence suggesting that SBRT may improve treatment for patients with spine metastases, more research is needed to determine if it is better than CRT. The first part of the randomized trial (phase II) looked at whether it was possible (feasible) to provide these treatments in cancer centres across Canada, by aiming to recruit 54 participants within 18 months. This part of the study was successfully completed in early 2017. The second component of this study, called a randomized phase III trial, is now underway. It involves recruiting another 124 participants to receive either CRT or SBRT, using the same study procedure as in the feasibility study. We will continue to obtain information about whether SBRT is better than CRT at controlling pain.

Official Title
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A Randomized Phase II/III Study Comparing Stereotactic Body Radiotherapy(SBRT) Versus Conventional Palliative Radiotherapy (CRT) for Patients With Spinal Metastases

Conditions
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Spinal Metastases

Intervention / Treatment
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* Radiation: 20 Gy in 5 fractions
* Radiation: Conventional SBRT: 24 Gy in 2 fractions


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic diagnosis of cancer (excluding seminoma, small cell lung cancer and hematologic primaries). Spinal metastasis documented with MRI and suitable for treatment with radiotherapy with the following characteristics: Painful, as defined by a pain score ≥ 2 for worst pain in the planned target treatment volume; ≤ 3 consecutive spinal segments involved by tumour to be included in the planned target volume. The patient may have other spinal metaastases to be treated as per the radiation oncologist's discretion, but the eligible spinal metastatic site has to be one where there is pain and no more than 3 consecutive segments to be included as clinical target volume and appropriate for either 20 Gy in 5 fractions or 24 Gy in 2 fractions per the randomization. There is no plan to change the pain medication on the first day of protocol treatment with radiotherapy. ECOG Performance Status 0-2. Seen by a radiation oncologist and judged to be appropriate for participation in this study including ability to tolerate protocol radiotherapy (SBRT or CRT). Age of 18 years or older. Patient is able and willing to complete the Patient Diary (pain and analgesic use). Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaire in either English or French. The baseline assessment must be completed within required timelines, prior to randomization. Inability (illiteracy in English or French, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible. Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate. Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up. In accordance with CCTG policy, protocol treatment is to begin within 3 weeks of patient randomization. From the time of successful treatment planning, no more than 12 days can elapse before the first fraction of radiotherapy is delivered. Women/men of childbearing potential must have agreed to use a highly effective contraceptive method. A woman is considered to be of childbearing potential if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, effective contraception also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures. Women of childbearing potential will have a pregnancy test to determine eligibility as part of the Pre-Study Evaluation; this may include an ultrasound to rule-out pregnancy if a false-positive is suspected. For example, when beta-human chorionic gonadotropin is high and partner is vasectomized, it may be associated with tumour production of hCG, as seen with some cancers. Patient will be considered eligible if an ultrasound is negative for pregnancy. Exclusion Criteria: Patients who have a pacemaker, such that MRI cannot be performed or treatment cannot be delivered safely. Patients with prior treatment with any radionuclide within 30 days prior to randomization. Patients with prior radiation to the spinal segment intended to be treated with protocol radiotherapy such that the protocol therapy cannot be delivered as intended. Patients with prior surgery to the spinal segment intended to be treated with protocol radiotherapy. Patients who have received chemotherapy within 1 week prior to administration of protocol radiotherapy or who are expected/planned to receive chemotherapy within one week of completing protocol radiotherapy. Centre guidelines regarding administration of targeted non-cytotoxic therapy must be followed with the proviso that no systemic anticancer therapy should be administered within 24 hours prior to and post-radiotherapy. Endocrine therapy may be administered during radiotherapy as per the discretion of the treating physician. Patients with spine instability as judged by a Spinal Instability Neoplastic Score (SINS) of more than 12. Patients with symptomatic spinal cord compression or cauda equina syndrome resulting from bony compression or epidural compression of the spinal cord and cauda equina, respectively. Symptomatic refers to neurolic deficit in the form of motor, bowel or bladder dysfunction. 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Conventional Radiotherapy<br>Standard Conventional Radiotherapy (CRT) 20 Gy in 5 fractions | Radiation: 20 Gy in 5 fractions<br> <br> |
| Experimental: Stereotactic Body Radiotherapy<br>Stereotactic Body Radiotherapy (SBRT) 24 Gy in 2 fractions | Radiation: Conventional SBRT: 24 Gy in 2 fractions<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase III: Complete Pain Response at 3 Months Post-radiation | A Complete Pain Response is defined as a pain score of zero (0) at the treated site with no concomitant increase in analgesic intake (stable or reducing analgesics in daily oral morphine equivalent) . | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria | A Complete Pain Response is defined as a pain score of zero (0) at the treated site with no concomitant increase in analgesic intake (stable or reducing analgesics in daily oral morphine equivalent) . | 6 months post radiation | 
| Radiation Site Progression-free Survival Rate at 6 Months Using MRI Imaging | Radiation site progression was defined as: Gross unequivocal increase in tumor volume or linear dimension > 20%. Any new or progressive tumor within the epidural space. Neurologic deterioration attributable to pre-existing epidural disease with equivocal increased epidural disease dimensions on MRI. | 6 months. | 
| Overall Survival Rate at 6 Months | Proportion of participants who were alive at 6 months in study. | 6 months post radiation |