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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Spinal Metastases	Radiation: 20 Gy in 5 fractions; Radiation: Conventional SBRT: 24 Gy in 2 fractions	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 229 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Randomized Phase II/III Study Comparing Stereotactic Body Radiotherapy(SBRT) Versus Conventional Palliative Radiotherapy (CRT) for Patients With Spinal Metastases
• Actual Study Start Date: January 4, 2016
• Actual Primary Completion Date: July 21, 2020
• Actual Study Completion Date: August 16, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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) .

Secondary Outcome Measures :

1. 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) .
2. 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.
3. Overall Survival Rate at 6 Months [ Time Frame: 6 months post radiation ]
   Proportion of participants who were alive at 6 months in study.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Australia, Aucklund

Auckland City Hospital

Grafton, Aucklund, Australia, 1023

Australia, New South Wales

Liverpool Cancer Therapy Centre, Liverpool Hospital

Liverpool, New South Wales, Australia, 2170

Australia, Queensland

Princess Alexandra Hospital

Brisbane, Queensland, Australia, 4102

Australia, South Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia, 5000

Australia, Victoria

Peter McCallum Cancer Institute

Melbourne, Victoria, Australia, 3002

Peter Mac - Sunshine Hospital

St Albans, Victoria, Australia, 3021

Australia

Canberra Hospital

Garran, Australia, ACT 2605

Royal Brisbane and Womens Hospital

Herston, Australia, 4029

Canada, Alberta

Tom Baker Cancer Centre

Calgary, Alberta, Canada, T2N 4N2

Cross Cancer Institute

Edmonton, Alberta, Canada, T6G 1Z2

Canada, British Columbia

BCCA - Centre for the North

Prince George, British Columbia, Canada, V2M 7E9

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada, V5Z 4E6

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, Canada, V8R 6V5

Canada, Manitoba

CancerCare Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Ontario

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada, L8V 5C2

London Regional Cancer Program

London, Ontario, Canada, N6A 5W9

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada, K1H 8L6

Odette Cancer Centre

Toronto, Ontario, Canada, M4N 3M5

University Health Network

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada, H2X 3E4

CHUQ-Pavillon Hotel-Dieu de Quebec

Quebec City, Quebec, Canada, G1R 2J6

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, Canada, J1H 5N4

Sponsors and Collaborators

Canadian Cancer Trials Group

Trans Tasman Radiation Oncology Group

Investigators

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

  Study Documents (Full-Text)

Documents provided by Canadian Cancer Trials Group:

Study Protocol  [PDF] October 31, 2018

Statistical Analysis Plan  [PDF] July 7, 2020

Informed Consent Form  [PDF] October 31, 2018

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Canadian Cancer Trials Group
• ClinicalTrials.gov Identifier: NCT02512965
• Other Study ID Numbers: SC24
• First Posted: July 31, 2015
• Results First Posted: August 16, 2021
• Last Update Posted: February 13, 2024
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes