Spinal Metastases
Conditions
Brief summary
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
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.
Interventions
RADIATION20 Gy in 5 fractions
RADIATIONConventional SBRT: 24 Gy in 2 fractions
Sponsors
Trans Tasman Radiation Oncology Group
Canadian Cancer Trials Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase III: Complete Pain Response at 3 Months Post-radiation | 3 months | 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) . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria | 6 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) . |
| Radiation Site Progression-free Survival Rate at 6 Months Using MRI Imaging | 6 months. | 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. |
| Overall Survival Rate at 6 Months | 6 months post radiation | Proportion of participants who were alive at 6 months in study. |
Countries
Australia, Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Conventional Radiotherapy Standard Conventional Radiotherapy (CRT) 20 Gy in 5 fractions
20 Gy in 5 fractions | 115 |
| Stereotactic Body Radiotherapy Stereotactic Body Radiotherapy (SBRT) 24 Gy in 2 fractions
Conventional SBRT: 24 Gy in 2 fractions | 114 |
| Total | 229 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 4 |
Baseline characteristics
| Characteristic | Total | Standard Conventional Radiotherapy | Stereotactic Body Radiotherapy |
|---|---|---|---|
| Age, Continuous | 63.86 years STANDARD_DEVIATION 12.38 | 64.05 years STANDARD_DEVIATION 12.7 | 63.67 years STANDARD_DEVIATION 12.1 |
| ECOG Performance Status 0 | 30 Participants | 14 Participants | 16 Participants |
| ECOG Performance Status 1 | 180 Participants | 90 Participants | 90 Participants |
| ECOG Performance Status 2 | 19 Participants | 11 Participants | 8 Participants |
| Histology Radioresistant | 60 Participants | 30 Participants | 30 Participants |
| Histology Radiosensitive | 169 Participants | 85 Participants | 84 Participants |
| Mass on imaging Absent | 84 Participants | 43 Participants | 41 Participants |
| Mass on imaging Present | 145 Participants | 72 Participants | 73 Participants |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Region of Enrollment Australia | 24 participants | 12 participants | 12 participants |
| Region of Enrollment Canada | 205 participants | 103 participants | 102 participants |
| Sex: Female, Male Female | 109 Participants | 54 Participants | 55 Participants |
| Sex: Female, Male Male | 120 Participants | 61 Participants | 59 Participants |
| Spinal instability neoplastic score (SINS) 0-6 | 103 Participants | 46 Participants | 57 Participants |
| Spinal instability neoplastic score (SINS) > 6 | 126 Participants | 69 Participants | 57 Participants |
| Worst pain score 10 | 15 Participants | 5 Participants | 10 Participants |
| Worst pain score 2 | 23 Participants | 11 Participants | 12 Participants |
| Worst pain score 3 | 33 Participants | 14 Participants | 19 Participants |
| Worst pain score 4 | 33 Participants | 18 Participants | 15 Participants |
| Worst pain score 5 | 34 Participants | 16 Participants | 18 Participants |
| Worst pain score 6 | 26 Participants | 12 Participants | 14 Participants |
| Worst pain score 7 | 27 Participants | 17 Participants | 10 Participants |
| Worst pain score 8 | 23 Participants | 12 Participants | 11 Participants |
| Worst pain score 9 | 15 Participants | 10 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 30 / 115 | 25 / 114 |
| other Total, other adverse events | 17 / 115 | 9 / 110 |
| serious Total, serious adverse events | 4 / 115 | 3 / 110 |
Outcome results
Primary
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) .
Time frame: 3 months
Population: ITT population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Conventional Radiotherapy | Phase III: Complete Pain Response at 3 Months Post-radiation | PR | 29 Participants |
| Standard Conventional Radiotherapy | Phase III: Complete Pain Response at 3 Months Post-radiation | PD | 14 Participants |
| Standard Conventional Radiotherapy | Phase III: Complete Pain Response at 3 Months Post-radiation | SD | 34 Participants |
| Standard Conventional Radiotherapy | Phase III: Complete Pain Response at 3 Months Post-radiation | In-evalable | 22 Participants |
| Standard Conventional Radiotherapy | Phase III: Complete Pain Response at 3 Months Post-radiation | CR | 16 Participants |
| Stereotactic Body Radiotherapy | Phase III: Complete Pain Response at 3 Months Post-radiation | In-evalable | 16 Participants |
| Stereotactic Body Radiotherapy | Phase III: Complete Pain Response at 3 Months Post-radiation | CR | 40 Participants |
| Stereotactic Body Radiotherapy | Phase III: Complete Pain Response at 3 Months Post-radiation | PR | 20 Participants |
| Stereotactic Body Radiotherapy | Phase III: Complete Pain Response at 3 Months Post-radiation | SD | 27 Participants |
| Stereotactic Body Radiotherapy | Phase III: Complete Pain Response at 3 Months Post-radiation | PD | 7 Participants |
p-value: 0.000295% CI: [1.79, 6.69]Cochran-Mantel-Haenszel
Secondary
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) .
Time frame: 6 months post radiation
Population: ITT population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Conventional Radiotherapy | Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria | PR | 18 Participants |
| Standard Conventional Radiotherapy | Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria | PD | 8 Participants |
| Standard Conventional Radiotherapy | Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria | SD | 32 Participants |
| Standard Conventional Radiotherapy | Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria | In-evaluable | 39 Participants |
| Standard Conventional Radiotherapy | Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria | CR | 18 Participants |
| Stereotactic Body Radiotherapy | Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria | In-evaluable | 36 Participants |
| Stereotactic Body Radiotherapy | Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria | CR | 37 Participants |
| Stereotactic Body Radiotherapy | Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria | PR | 10 Participants |
| Stereotactic Body Radiotherapy | Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria | SD | 26 Participants |
| Stereotactic Body Radiotherapy | Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria | PD | 5 Participants |
p-value: 0.003695% CI: [1.35, 4.85]Cochran-Mantel-Haenszel
Secondary
Overall Survival Rate at 6 Months
Proportion of participants who were alive at 6 months in study.
Time frame: 6 months post radiation
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Conventional Radiotherapy | Overall Survival Rate at 6 Months | 0.73 proportion of all participants |
| Stereotactic Body Radiotherapy | Overall Survival Rate at 6 Months | 0.77 proportion of all participants |
p-value: 0.4795% CI: [0.48, 1.4]Log Rank
Secondary
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.
Time frame: 6 months.
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Conventional Radiotherapy | Radiation Site Progression-free Survival Rate at 6 Months Using MRI Imaging | 0.69 proportion of participants by arm |
| Stereotactic Body Radiotherapy | Radiation Site Progression-free Survival Rate at 6 Months Using MRI Imaging | 0.75 proportion of participants by arm |
p-value: 0.2695% CI: [0.46, 1.24]Log Rank