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

• ClinicalTrials.gov Identifier: NCT02512965
• Recruitment Status: Completed
• First Posted: July 31, 2015
• Results First Posted: August 16, 2021
• Last Update Posted: February 13, 2024
• Sponsor: Canadian Cancer Trials Group
• Collaborator: Trans Tasman Radiation Oncology Group
• Information provided by (Responsible Party): Canadian Cancer Trials Group

Tracking Information

• First Submitted Date: July 27, 2015
• First Posted Date: July 31, 2015
• Results First Submitted Date: May 11, 2021
• Results First Posted Date: August 16, 2021
• Last Update Posted Date: February 13, 2024
• Actual Study Start Date: January 4, 2016
• Actual Primary Completion Date: July 21, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 13, 2021)

Phase III: Complete Pain Response at 3 Months Post-radiation [ Time Frame: 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) .

• Original Primary Outcome Measures (submitted: July 30, 2015): Number of participants randomize with spinal metastases to Stereotactic Body Radiotherapy (SBRT) or Standard Conventional Radiotherapy (CRT) within a Canadian multicentre setting [ Time Frame: 18 months ]

Current Secondary Outcome Measures (submitted: August 13, 2021)

• Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 6 months post radiation ]
  Proportion of participants who were alive at 6 months in study.

Original Secondary Outcome Measures (submitted: July 30, 2015)

• Complete pain response based on the International Bone Metastases Consensus Working Party Criteria [ Time Frame: 3 and 6 months post radiation ]
• Progression-free survival using MRI imaging [ Time Frame: 3 and 6 months post radiation ]
• Number and severity of adverse events using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4.0) [ Time Frame: 24 months ]
• Health-related Quality of Life measured by the EORTC QLQ-C30 and QLQ-BM22 instruments [ Time Frame: 24 months ]
• Radiotherapy Quality Assurance compliance at 3 time points. Site credentialing, Prospective centre based individual pre-treatment case review and Retrospective external individual post-treatment case review. [ Time Frame: 24 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Comparing Stereotactic Body Radiotherapy vs Conventional Palliative Radiotherapy (CRT) for Spinal Metastases
• Official Title: A Randomized Phase II/III Study Comparing Stereotactic Body Radiotherapy(SBRT) Versus Conventional Palliative Radiotherapy (CRT) for Patients With Spinal Metastases
• 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.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Spinal Metastases

Intervention

• Radiation: 20 Gy in 5 fractions
• Radiation: Conventional SBRT: 24 Gy in 2 fractions

Study Arms

• Active Comparator: Standard Conventional Radiotherapy
  Standard Conventional Radiotherapy (CRT) 20 Gy in 5 fractions
  Intervention: Radiation: 20 Gy in 5 fractions
• Experimental: Stereotactic Body Radiotherapy
  Stereotactic Body Radiotherapy (SBRT) 24 Gy in 2 fractions
  Intervention: Radiation: Conventional SBRT: 24 Gy in 2 fractions

Publications *

• Sahgal A, Myrehaug SD, Siva S, Masucci GL, Maralani PJ, Brundage M, Butler J, Chow E, Fehlings MG, Foote M, Gabos Z, Greenspoon J, Kerba M, Lee Y, Liu M, Liu SK, Thibault I, Wong RK, Hum M, Ding K, Parulekar WR; trial investigators. Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. Lancet Oncol. 2021 Jul;22(7):1023-1033. doi: 10.1016/S1470-2045(21)00196-0. Epub 2021 Jun 11.
• Tseng CL, Soliman H, Myrehaug S, Lee YK, Ruschin M, Atenafu EG, Campbell M, Maralani P, Yang V, Yee A, Sahgal A. Imaging-Based Outcomes for 24 Gy in 2 Daily Fractions for Patients with de Novo Spinal Metastases Treated With Spine Stereotactic Body Radiation Therapy (SBRT). Int J Radiat Oncol Biol Phys. 2018 Nov 1;102(3):499-507. doi: 10.1016/j.ijrobp.2018.06.047. Epub 2018 Jul 10.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 27, 2019): 229
• Original Estimated Enrollment (submitted: July 30, 2015): 54
• Actual Study Completion Date: August 16, 2021
• Actual Primary Completion Date: July 21, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada

Administrative Information

• NCT Number: NCT02512965
• Other Study ID Numbers: SC24
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Canadian Cancer Trials Group
• Original Responsible Party: NCIC Clinical Trials Group
• Current Study Sponsor: Canadian Cancer Trials Group
• Original Study Sponsor: NCIC Clinical Trials Group
• Collaborators: Trans Tasman Radiation Oncology Group

Investigators

• Study Chair: Arjun Sahgal; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto ON

• PRS Account: Canadian Cancer Trials Group
• Verification Date: August 2021