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

• Sponsor: Canadian Cancer Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT02512965
• Collaborator: Trans Tasman Radiation Oncology Group (Other)
• Enrollment: 229
• Locations: 22
• Arms: 2
• Actual Duration (Months): 72.6
• Patients Per Site: 10.4
• Patients Per Site Per Month: 0.1

Study Details

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	N/A

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
• 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: Jul 28, 2015
• Actual Primary Completion Date: Jul 21, 2020
• Actual Study Completion Date: Aug 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 [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 [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 [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 [6 months post radiation]

   Proportion of participants who were alive at 6 months in study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Auckland City Hospital	Grafton	Aucklund	Australia	1023
2	Liverpool Cancer Therapy Centre, Liverpool Hospital	Liverpool	New South Wales	Australia	2170
3	Princess Alexandra Hospital	Brisbane	Queensland	Australia	4102
4	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
5	Peter McCallum Cancer Institute	Melbourne	Victoria	Australia	3002
6	Peter Mac - Sunshine Hospital	St Albans	Victoria	Australia	3021
7	Canberra Hospital	Garran		Australia	ACT 2605
8	Royal Brisbane and Womens Hospital	Herston		Australia	4029
9	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
10	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
11	BCCA - Centre for the North	Prince George	British Columbia	Canada	V2M 7E9
12	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
13	BCCA - Vancouver Island Cancer Centre	Victoria	British Columbia	Canada	V8R 6V5
14	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
15	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
16	London Regional Cancer Program	London	Ontario	Canada	N6A 5W9
17	Ottawa Hospital Research Institute	Ottawa	Ontario	Canada	K1H 8L6
18	Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
19	University Health Network	Toronto	Ontario	Canada	M5G 2M9
20	CHUM-Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec	Canada	H2X 3E4
21	CHUQ-Pavillon Hotel-Dieu de Quebec	Quebec City	Quebec	Canada	G1R 2J6
22	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)

• Study Protocol - Oct 31, 2018
• Statistical Analysis Plan - Jul 7, 2020
• Informed Consent Form - Oct 31, 2018

More Information

Publications

None provided.

• Responsible Party: Canadian Cancer Trials Group
• ClinicalTrials.gov Identifier: NCT02512965
• Other Study ID Numbers: SC24
• First Posted: Jul 31, 2015
• Last Update Posted: Aug 17, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• 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

Study Results

Participant Flow

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
NOT COMPLETED	0	4

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 Participants	115	114	229
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.05 (12.7)	63.67 (12.1)	63.86 (12.38)
Sex: Female, Male (Count of Participants)
Female	54 47%	55 48.2%	109 47.6%
Male	61 53%	59 51.8%	120 52.4%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Canada	103 89.6%	102 89.5%	205 89.5%
Australia	12 10.4%	12 10.5%	24 10.5%
ECOG Performance Status (Count of Participants)
0	14 12.2%	16 14%	30 13.1%
1	90 78.3%	90 78.9%	180 78.6%
2	11 9.6%	8 7%	19 8.3%
Worst pain score (Count of Participants)
2	11 9.6%	12 10.5%	23 10%
3	14 12.2%	19 16.7%	33 14.4%
4	18 15.7%	15 13.2%	33 14.4%
5	16 13.9%	18 15.8%	34 14.8%
6	12 10.4%	14 12.3%	26 11.4%
7	17 14.8%	10 8.8%	27 11.8%
8	12 10.4%	11 9.6%	23 10%
9	10 8.7%	5 4.4%	15 6.6%
10	5 4.3%	10 8.8%	15 6.6%
Spinal instability neoplastic score (SINS) (Count of Participants)
0-6	46 40%	57 50%	103 45%
> 6	69 60%	57 50%	126 55%
Histology (Count of Participants)
Radioresistant	30 26.1%	30 26.3%	60 26.2%
Radiosensitive	85 73.9%	84 73.7%	169 73.8%
Mass on imaging (Count of Participants)
Absent	43 37.4%	41 36%	84 36.7%
Present	72 62.6%	73 64%	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
Measure Participants	115	114
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%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Conventional Radiotherapy, Stereotactic Body Radiotherapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	2-sided, adjusted for stratification factors at randomization.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.46
	Confidence Interval	(2-Sided) 95%; 1.79 to 6.69
	Parameter Dispersion	Type: Value:
	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
Measure Participants	115	114
CR	18 15.7%	37 32.5%
PR	18 15.7%	10 8.8%
SD	32 27.8%	26 22.8%
PD	8 7%	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
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0036
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.56
	Confidence Interval	(2-Sided) 95%; 1.35 to 4.85
	Parameter Dispersion	Type: Value:
	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
Measure Participants	115	114
Number (95% Confidence Interval) [proportion of participants by arm]	0.69 0.6%	0.75 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Conventional Radiotherapy, Stereotactic Body Radiotherapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments
	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
	Parameter Dispersion	Type: Value:
	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
Measure Participants	115	114
Number (95% Confidence Interval) [proportion of all participants]	0.73 0.6%	0.77 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Conventional Radiotherapy, Stereotactic Body Radiotherapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.47
	Comments	2-sided p-value adjusted for stratification factors at randomization.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.48 to 1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 (%)	# Events	Affected / at Risk (%)	# Events
Total	30/115 (26.1%)		25/114 (21.9%)
Serious Adverse Events
	Standard Conventional Radiotherapy		Stereotactic Body Radiotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/115 (3.5%)		3/110 (2.7%)
Gastrointestinal disorders
Dysphagia	0/115 (0%)	0	1/110 (0.9%)	1
Esophagitis	1/115 (0.9%)	1	0/110 (0%)	0
Nausea	1/115 (0.9%)	1	0/110 (0%)	0
General disorders
Fatigue	1/115 (0.9%)	1	0/110 (0%)	0
Pain	1/115 (0.9%)	1	0/110 (0%)	0
Injury, poisoning and procedural complications
Spinal fracture	1/115 (0.9%)	1	1/110 (0.9%)	1
Metabolism and nutrition disorders
Dehydration	1/115 (0.9%)	1	0/110 (0%)	0
Musculoskeletal and connective tissue disorders
Neck pain	0/115 (0%)	0	1/110 (0.9%)	1
Other (Not Including Serious) Adverse Events
	Standard Conventional Radiotherapy		Stereotactic Body Radiotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/115 (14.8%)		9/110 (8.2%)
General disorders
Pain	6/115 (5.2%)	6	3/110 (2.7%)	3
Musculoskeletal and connective tissue disorders
Back pain	11/115 (9.6%)	11	6/110 (5.5%)	6

Limitations/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.