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 Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Spinal Metastases
• Interventions: Radiation: 20 Gy in 5 fractions; Radiation: Conventional SBRT: 24 Gy in 2 fractions
• Enrollment: 229

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Standard Conventional Radiotherapy	Stereotactic Body Radiotherapy
Arm/Group Description	Standard Conventional Radiotherapy (CRT) 20 Gy in 5 fractions 20 Gy in 5 fractions	Stereotactic Body Radiotherapy (SBRT) 24 Gy in 2 fractions Conventional SBRT: 24 Gy in 2 fractions
Period Title: Overall Study
Started	115	114
Completed	115	110 [1]
Not Completed	0	4
Reason Not Completed
Withdrawal by Subject	0	4
[1] 4 patients did not receive any dose of the assigned treatment.

Baseline Characteristics

Arm/Group Title		Standard Conventional Radiotherapy	Stereotactic Body Radiotherapy	Total
Arm/Group Description		Standard Conventional Radiotherapy (CRT) 20 Gy in 5 fractions 20 Gy in 5 fractions	Stereotactic Body Radiotherapy (SBRT) 24 Gy in 2 fractions Conventional SBRT: 24 Gy in 2 fractions	Total of all reporting groups
Overall Number of Baseline Participants		115	114	229
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	115 participants	114 participants	229 participants
		64.05 (12.7)	63.67 (12.1)	63.86 (12.38)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	115 participants	114 participants	229 participants
	Female	54 47.0%	55 48.2%	109 47.6%
	Male	61 53.0%	59 51.8%	120 52.4%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants	0 participants	0 participants
				0
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Canada	Number Analyzed	115 participants	114 participants	229 participants
		103	102	205
Australia	Number Analyzed	115 participants	114 participants	229 participants
		12	12	24
ECOG Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
0	Number Analyzed	115 participants	114 participants	229 participants
		14 12.2%	16 14.0%	30 13.1%
1	Number Analyzed	115 participants	114 participants	229 participants
		90 78.3%	90 78.9%	180 78.6%
2	Number Analyzed	115 participants	114 participants	229 participants
		11 9.6%	8 7.0%	19 8.3%
		[1] Measure Description: 0: Fully active, able to carry on all pre-disease performance without restriction.; Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.; Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours.
Worst pain score [1]; Measure Type: Count of Participants; Unit of measure: Participants
2	Number Analyzed	115 participants	114 participants	229 participants
		11 9.6%	12 10.5%	23 10.0%
3	Number Analyzed	115 participants	114 participants	229 participants
		14 12.2%	19 16.7%	33 14.4%
4	Number Analyzed	115 participants	114 participants	229 participants
		18 15.7%	15 13.2%	33 14.4%
5	Number Analyzed	115 participants	114 participants	229 participants
		16 13.9%	18 15.8%	34 14.8%
6	Number Analyzed	115 participants	114 participants	229 participants
		12 10.4%	14 12.3%	26 11.4%
7	Number Analyzed	115 participants	114 participants	229 participants
		17 14.8%	10 8.8%	27 11.8%
8	Number Analyzed	115 participants	114 participants	229 participants
		12 10.4%	11 9.6%	23 10.0%
9	Number Analyzed	115 participants	114 participants	229 participants
		10 8.7%	5 4.4%	15 6.6%
10	Number Analyzed	115 participants	114 participants	229 participants
		5 4.3%	10 8.8%	15 6.6%
		[1] Measure Description: Pain score range from 0 (no pain) to 10 (pain as bad as you can imagine).
Spinal instability neoplastic score (SINS) [1]; Measure Type: Count of Participants; Unit of measure: Participants
0-6	Number Analyzed	115 participants	114 participants	229 participants
		46 40.0%	57 50.0%	103 45.0%
> 6	Number Analyzed	115 participants	114 participants	229 participants
		69 60.0%	57 50.0%	126 55.0%
		[1] Measure Description: SINS is used to assess the stability of the spine in patients with metastatic spinal cord compression. It ranges from 0 to 18; with 0-6 as stable, 7 - 12 as indeterminate and 13-18 instable.
Histology; Measure Type: Count of Participants; Unit of measure: Participants
Radioresistant	Number Analyzed	115 participants	114 participants	229 participants
		30 26.1%	30 26.3%	60 26.2%
Radiosensitive	Number Analyzed	115 participants	114 participants	229 participants
		85 73.9%	84 73.7%	169 73.8%
Mass on imaging; Measure Type: Count of Participants; Unit of measure: Participants
Absent	Number Analyzed	115 participants	114 participants	229 participants
		43 37.4%	41 36.0%	84 36.7%
Present	Number Analyzed	115 participants	114 participants	229 participants
		72 62.6%	73 64.0%	145 63.3%

Outcome Measures

1. Primary Outcome

Title	Phase III: Complete Pain Response at 3 Months Post-radiation
Description	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

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Standard Conventional Radiotherapy	Stereotactic Body Radiotherapy
Arm/Group Description:	Standard Conventional Radiotherapy (CRT) 20 Gy in 5 fractions 20 Gy in 5 fractions	Stereotactic Body Radiotherapy (SBRT) 24 Gy in 2 fractions Conventional SBRT: 24 Gy in 2 fractions
Overall Number of Participants Analyzed	115	114
Measure Type: Count of Participants; Unit of Measure: Participants
CR	16 13.9%	40 35.1%
PR	29 25.2%	20 17.5%
SD	34 29.6%	27 23.7%
PD	14 12.2%	7 6.1%
In-evalable	22 19.1%	16 14.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Conventional Radiotherapy, Stereotactic Body Radiotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0002
	Comments	2-sided, adjusted for stratification factors at randomization.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.46
	Confidence Interval	(2-Sided) 95%; 1.79 to 6.69
	Estimation Comments	Mantel-Haenszel estimate stratified by stratification factor at randomization.

2. Secondary Outcome

Title	Complete Pain Response at 6 Months Post Radiation Based on the International Bone Metastases Consensus Working Party Criteria
Description	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

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Standard Conventional Radiotherapy	Stereotactic Body Radiotherapy
Arm/Group Description:	Standard Conventional Radiotherapy (CRT) 20 Gy in 5 fractions 20 Gy in 5 fractions	Stereotactic Body Radiotherapy (SBRT) 24 Gy in 2 fractions Conventional SBRT: 24 Gy in 2 fractions
Overall Number of Participants Analyzed	115	114
Measure Type: Count of Participants; Unit of Measure: Participants
CR	18 15.7%	37 32.5%
PR	18 15.7%	10 8.8%
SD	32 27.8%	26 22.8%
PD	8 7.0%	5 4.4%
In-evaluable	39 33.9%	36 31.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Conventional Radiotherapy, Stereotactic Body Radiotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0036
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.56
	Confidence Interval	(2-Sided) 95%; 1.35 to 4.85
	Estimation Comments	Mantel-Haenszel estimate stratified by stratification factors at randomization.

3. Secondary Outcome

Title	Radiation Site Progression-free Survival Rate at 6 Months Using MRI Imaging
Description	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.

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Standard Conventional Radiotherapy	Stereotactic Body Radiotherapy
Arm/Group Description:	Standard Conventional Radiotherapy (CRT) 20 Gy in 5 fractions 20 Gy in 5 fractions	Stereotactic Body Radiotherapy (SBRT) 24 Gy in 2 fractions Conventional SBRT: 24 Gy in 2 fractions
Overall Number of Participants Analyzed	115	114
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of participants by arm
	0.69; (0.60 to 0.77)	0.75; (0.65 to 0.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Conventional Radiotherapy, Stereotactic Body Radiotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.26
	Comments	[Not Specified]
	Method	Log Rank
	Comments	2-sided p-value adjusted for stratification factors at randomization.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.46 to 1.24
	Estimation Comments	Estimate adjusted for stratification factors at randopmization.

4. Secondary Outcome

Title	Overall Survival Rate at 6 Months
Description	Proportion of participants who were alive at 6 months in study.
Time Frame	6 months post radiation

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Standard Conventional Radiotherapy	Stereotactic Body Radiotherapy
Arm/Group Description:	Standard Conventional Radiotherapy (CRT) 20 Gy in 5 fractions 20 Gy in 5 fractions	Stereotactic Body Radiotherapy (SBRT) 24 Gy in 2 fractions Conventional SBRT: 24 Gy in 2 fractions
Overall Number of Participants Analyzed	115	114
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of all participants
	0.73; (0.64 to 0.81)	0.77; (0.68 to 0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Conventional Radiotherapy, Stereotactic Body Radiotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.47
	Comments	2-sided p-value adjusted for stratification factors at randomization.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.48 to 1.40
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	6 months.
Adverse Event Reporting Description	Adverse events graded according to CTCAE V4.0 In the comments, it says that the number of patients in safety analysis does not agree with the patients flow chart. However, they are indeed different. As 115 and 114 were randomized to CRT and SBRT arm respectively, but there were 4 patients on SBRT arm did not receive any treatment, which leads to the difference. (Safety analyses were based on as-treated population)
Arm/Group Title	Standard Conventional Radiotherapy		Stereotactic Body Radiotherapy
Arm/Group Description	Standard Conventional Radiotherapy (CRT) 20 Gy in 5 fractions 20 Gy in 5 fractions		Stereotactic Body Radiotherapy (SBRT) 24 Gy in 2 fractions Conventional SBRT: 24 Gy in 2 fractions
All-Cause Mortality
	Standard Conventional Radiotherapy		Stereotactic Body Radiotherapy
	Affected / at Risk (%)		Affected / at Risk (%)
Total	30/115 (26.09%)		25/114 (21.93%)
Serious Adverse Events
	Standard Conventional Radiotherapy		Stereotactic Body Radiotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/115 (3.48%)		3/110 (2.73%)
Gastrointestinal disorders
Dysphagia † 1	0/115 (0.00%)	0	1/110 (0.91%)	1
Esophagitis † 1	1/115 (0.87%)	1	0/110 (0.00%)	0
Nausea † 1	1/115 (0.87%)	1	0/110 (0.00%)	0
General disorders
Fatigue † 1	1/115 (0.87%)	1	0/110 (0.00%)	0
Pain † 1	1/115 (0.87%)	1	0/110 (0.00%)	0
Injury, poisoning and procedural complications
Spinal fracture † 1	1/115 (0.87%)	1	1/110 (0.91%)	1
Metabolism and nutrition disorders
Dehydration † 1	1/115 (0.87%)	1	0/110 (0.00%)	0
Musculoskeletal and connective tissue disorders
Neck pain † 1	0/115 (0.00%)	0	1/110 (0.91%)	1
1 Term from vocabulary, CTCAE V4.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Standard Conventional Radiotherapy		Stereotactic Body Radiotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/115 (14.78%)		9/110 (8.18%)
General disorders
Pain † 1	6/115 (5.22%)	6	3/110 (2.73%)	3
Musculoskeletal and connective tissue disorders
Back pain † 1	11/115 (9.57%)	11	6/110 (5.45%)	6
1 Term from vocabulary, CTCAE V4.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Keyue Ding
• Organization: Canadian Cancer Trials Group
• Phone: 16135336430 ext 77705
• EMail: kding@ctg.queensu.ca

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 Submitted: July 27, 2015
• First Posted: July 31, 2015
• Results First Submitted: May 11, 2021
• Results First Posted: August 16, 2021
• Last Update Posted: February 13, 2024