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Single vs Multiple-Fraction Therapy in Treating Patients With Previously Irradiated Painful Bone Metastases

Primary Purpose

Metastatic Cancer, Pain

Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
radiation therapy
Sponsored by
NCIC Clinical Trials Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Cancer focused on measuring bone metastases, pain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed malignancy Diagnosis by needle biopsy, bone marrow biopsy, cytology, or surgical biopsy or resection Bone metastases at clinically painful areas confirmed by any of the following: Plain radiographs Radionuclide bone scans CT scans Magnetic resonance imaging Worst pain score of β‰₯ 2/10 using the baseline Brief Pain Inventory Pain arising from previously irradiated metastases and not from progressive disease in adjoining or remote areas Initial radiotherapy field is reproducible for re-irradiation Current treatment field for palliative radiotherapy must be the same size or smaller than the initial treatment field No clinical or radiological evidence of pathological fractures in the target site extremities. No radiological evidence of high-risk lesions for pathological fractures in the extremities (lytic lesions > 3cm or > 50% cortical erosion of bone diameter) if target site AND patient is a candidate for surgical intervention. No clinical or radiological evidence of spinal cord compression at target site. PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 50-100% Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Other Not pregnant or nursing Fertile patients must use effective barrier contraception Able and willing to complete quality of life questionnaire in English, French, Dutch, or Spanish (if randomized by Canadian, Dutch, French or RTOG centre) Must be accessible for treatment follow-up Informed consent PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy See Disease Characteristics No more than 1 prior course of radiotherapy to the target site No prior radiotherapy dose β‰₯ 24 Gy in 6 fractions, 27 Gy in 8 fractions, or 30 Gy in 10 fractions to the spine or any part of the pelvis encompassing small or large bowel and/or the rectum, if these sites are being treated on study Initial doses of 24 Gy in 6 fractions, 27 Gy in 8 fractions or 30 Gy in 10 fractions to the acetabulum or hip and proximal femur allowed as long as the medial field border of the initial treatment did not cross midline No prior radiotherapy dose > 30Gy in 10 fractions to the ribs or extremities if these sites are being treated on study More than 30 days since prior strontium chloride Sr 89 More than 30 days since prior half-body radiotherapy, including the current re-irradiation field At least 4 weeks since initial radiotherapy Surgery No prior palliative surgery in treatment area No concurrent surgical intervention on treatment area Other No prior participation on this protocol No plan to make an immediate change in analgesic regimen

Sites / Locations

  • Tom Baker Cancer Centre
  • The Vitalite Health Network - Dr. Leon Richard
  • Juravinski Cancer Centre at Hamilton Health Sciences
  • Cancer Centre of Southeastern Ontario at Kingston
  • Grand River Regional Cancer Centre
  • Thunder Bay Regional Health Science Centre
  • Odette Cancer Centre
  • Univ. Health Network-Princess Margaret Hospital
  • CHUM - Hopital Notre-Dame
  • McGill University - Dept. Oncology
  • Centre hospitalier universitaire de Sherbrooke
  • Allan Blair Cancer Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I

Arm II

Arm Description

Patients receive single-fraction radiotherapy (8 Gy) on day 1.

Patients receive multiple-fraction radiotherapy (to a total of 20 Gy) over 5 days or over 8 days if re-irradiation of the spine and/or whole pelvis is involved AND prior initial radiotherapy was given in multiple fractions.

Outcomes

Primary Outcome Measures

Pain Relief Measured by the Brief Pain Inventory at 2 Months After Treatment
The primary endpoint of this study is Overall Response Rate (complete response and partial response) at two months after the first fraction of re-irradiation. A complete response was defined as a Brief Pain Inventory worst-pain score of zero with no associated increase in daily oral morphine equivalent. A partial response was defined as pain that persisted after treatment, either with a worst-pain score reduction of 2 or more and no increase in daily oral morphine equivalent consumption, or no increase in pain and a reduction in daily oral morphine equivalent consumption of at least 25%.

Secondary Outcome Measures

Full Information

First Posted
April 7, 2004
Last Updated
August 3, 2023
Sponsor
NCIC Clinical Trials Group
Collaborators
National Cancer Institute (NCI), Radiation Therapy Oncology Group, Trans Tasman Radiation Oncology Group, Cancer Research UK, Assistance Publique - HΓ΄pitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT00080912
Brief Title
Single vs Multiple-Fraction Therapy in Treating Patients With Previously Irradiated Painful Bone Metastases
Official Title
A Phase III International Randomized Trial Of Single Versus Multiple Fractions For Re-Irradiation Of Painful Bone Metastases
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
January 22, 2004 (Actual)
Primary Completion Date
April 10, 2013 (Actual)
Study Completion Date
January 16, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NCIC Clinical Trials Group
Collaborators
National Cancer Institute (NCI), Radiation Therapy Oncology Group, Trans Tasman Radiation Oncology Group, Cancer Research UK, Assistance Publique - HΓ΄pitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether single-fraction (single-dose) re-irradiation therapy is as effective as multiple-fraction (many small doses of radiation therapy) re-irradiation therapy in relieving bone pain caused by bone metastases. PURPOSE: This randomized phase III trial is studying single-dose radiation therapy to see if it works as well as multiple-dose radiation therapy in treating patients previously irradiated with painful bone metastases.
Detailed Description
OBJECTIVES: Primary Compare pain relief in patients undergoing single-fraction vs multiple-fraction re-irradiation of painful bone metastases at 2 months after treatment. Secondary Compare overall pain relief in patients treated with these regimens. Compare time to pain progression in patients treated with these regimens. Assess relationship between response to initial radiation and pain relief after re-irradiation in these patients. Compare changes in functional interference after re-irradiation using the Brief Pain Inventory in patients treated with these regimens. Compare quality of life of patients treated with these regimens (patients in Canada, France, the Netherlands, and patients registered through RTOG). Determine characteristics of non-responders (to both initial and re-irradiation) among patients treated with these regimens. Monitor the incidence of acute severe radiation-related side effects in patients treated with these regimens. Monitor the incidence of in-field pathological fractures and spinal cord compression in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to response to initial radiotherapy (yes vs no), initial fractionation (single fraction vs multiple fraction), and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive single-fraction radiotherapy (8Gy) on day 1. Arm II: Patients receive multiple-fraction radiotherapy (to a total of 20Gy) over 5 days or over 8 days if re-irradiation of the spine and/or whole pelvis is involved AND prior initial radiotherapy was given in multiple fractions. At least 4 weeks after the first re-treatment, patients in both arms may receive a second re-treatment at the discretion of the treating oncologist. Patients complete a Brief Pain Inventory questionnaire at baseline, on days 7 and 14, monthly during months 1-6, and at months 9 and 12. Acute Toxicities are assessed on days 7 and 14. Quality of Life is assessed at baseline and then monthly during months 1-6 for patients from participating groups. Patients are followed for up to 1 year. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 850 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Cancer, Pain
Keywords
bone metastases, pain

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
850 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients receive single-fraction radiotherapy (8 Gy) on day 1.
Arm Title
Arm II
Arm Type
Active Comparator
Arm Description
Patients receive multiple-fraction radiotherapy (to a total of 20 Gy) over 5 days or over 8 days if re-irradiation of the spine and/or whole pelvis is involved AND prior initial radiotherapy was given in multiple fractions.
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Intervention Description
Given in a single fraction or multiple fractions
Primary Outcome Measure Information:
Title
Pain Relief Measured by the Brief Pain Inventory at 2 Months After Treatment
Description
The primary endpoint of this study is Overall Response Rate (complete response and partial response) at two months after the first fraction of re-irradiation. A complete response was defined as a Brief Pain Inventory worst-pain score of zero with no associated increase in daily oral morphine equivalent. A partial response was defined as pain that persisted after treatment, either with a worst-pain score reduction of 2 or more and no increase in daily oral morphine equivalent consumption, or no increase in pain and a reduction in daily oral morphine equivalent consumption of at least 25%.
Time Frame
2 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed malignancy Diagnosis by needle biopsy, bone marrow biopsy, cytology, or surgical biopsy or resection Bone metastases at clinically painful areas confirmed by any of the following: Plain radiographs Radionuclide bone scans CT scans Magnetic resonance imaging Worst pain score of β‰₯ 2/10 using the baseline Brief Pain Inventory Pain arising from previously irradiated metastases and not from progressive disease in adjoining or remote areas Initial radiotherapy field is reproducible for re-irradiation Current treatment field for palliative radiotherapy must be the same size or smaller than the initial treatment field No clinical or radiological evidence of pathological fractures in the target site extremities. No radiological evidence of high-risk lesions for pathological fractures in the extremities (lytic lesions > 3cm or > 50% cortical erosion of bone diameter) if target site AND patient is a candidate for surgical intervention. No clinical or radiological evidence of spinal cord compression at target site. PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 50-100% Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Other Not pregnant or nursing Fertile patients must use effective barrier contraception Able and willing to complete quality of life questionnaire in English, French, Dutch, or Spanish (if randomized by Canadian, Dutch, French or RTOG centre) Must be accessible for treatment follow-up Informed consent PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy See Disease Characteristics No more than 1 prior course of radiotherapy to the target site No prior radiotherapy dose β‰₯ 24 Gy in 6 fractions, 27 Gy in 8 fractions, or 30 Gy in 10 fractions to the spine or any part of the pelvis encompassing small or large bowel and/or the rectum, if these sites are being treated on study Initial doses of 24 Gy in 6 fractions, 27 Gy in 8 fractions or 30 Gy in 10 fractions to the acetabulum or hip and proximal femur allowed as long as the medial field border of the initial treatment did not cross midline No prior radiotherapy dose > 30Gy in 10 fractions to the ribs or extremities if these sites are being treated on study More than 30 days since prior strontium chloride Sr 89 More than 30 days since prior half-body radiotherapy, including the current re-irradiation field At least 4 weeks since initial radiotherapy Surgery No prior palliative surgery in treatment area No concurrent surgical intervention on treatment area Other No prior participation on this protocol No plan to make an immediate change in analgesic regimen
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward LW Chow, MD
Organizational Affiliation
Toronto Sunnybrook Regional Cancer Centre
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
William F. Hartsell, MD
Organizational Affiliation
Advocate Good Samaratin Cancer Centre
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Daniel Roos, MD
Organizational Affiliation
Royal Adelaide Hospital Cancer Centre
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Yvette von der Linden
Organizational Affiliation
Radiotherapeutic Institution Friesland
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Peter Hoskin
Organizational Affiliation
Mount Vernon Cancer Centre
Official's Role
Study Chair
Facility Information:
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
The Vitalite Health Network - Dr. Leon Richard
City
Moncton
State/Province
New Brunswick
ZIP/Postal Code
E1C 8X3
Country
Canada
Facility Name
Juravinski Cancer Centre at Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Cancer Centre of Southeastern Ontario at Kingston
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 5P9
Country
Canada
Facility Name
Grand River Regional Cancer Centre
City
Kitchener
State/Province
Ontario
ZIP/Postal Code
N2G 1G3
Country
Canada
Facility Name
Thunder Bay Regional Health Science Centre
City
Thunder Bay
State/Province
Ontario
ZIP/Postal Code
P7B 6V4
Country
Canada
Facility Name
Odette Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Univ. Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
CHUM - Hopital Notre-Dame
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
Facility Name
McGill University - Dept. Oncology
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1S6
Country
Canada
Facility Name
Centre hospitalier universitaire de Sherbrooke
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Facility Name
Allan Blair Cancer Centre
City
Regina
State/Province
Saskatchewan
ZIP/Postal Code
S4T 7T1
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
16523812
Citation
Chow E, Hoskin PJ, Wu J, Roos D, van der Linden Y, Hartsell W, Vieth R, Wilson C, Pater J. A phase III international randomised trial comparing single with multiple fractions for re-irradiation of painful bone metastases: National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) SC 20. Clin Oncol (R Coll Radiol). 2006 Mar;18(2):125-8. doi: 10.1016/j.clon.2005.11.014. No abstract available.
Results Reference
background
PubMed Identifier
24369114
Citation
Chow E, van der Linden YM, Roos D, Hartsell WF, Hoskin P, Wu JS, Brundage MD, Nabid A, Tissing-Tan CJ, Oei B, Babington S, Demas WF, Wilson CF, Meyer RM, Chen BE, Wong RK. Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial. Lancet Oncol. 2014 Feb;15(2):164-71. doi: 10.1016/S1470-2045(13)70556-4. Epub 2013 Dec 23.
Results Reference
result
PubMed Identifier
29102263
Citation
Chow R, Ding K, Ganesh V, Meyer RM, van der Linden YM, Roos D, Hartsell WF, Hoskin P, Wu JSY, Nabid A, van Acht M, Wanders R, Babington S, Demas WF, Wilson CF, Wong RKS, Brundage M, Zhu L, Chow E. Gender and age make no difference in the re-irradiation of painful bone metastases: A secondary analysis of the NCIC CTG SC.20 randomized trial. Radiother Oncol. 2018 Mar;126(3):541-546. doi: 10.1016/j.radonc.2017.10.006. Epub 2017 Nov 5.
Results Reference
derived
PubMed Identifier
25349296
Citation
Chow E, Meyer RM, Chen BE, van der Linden YM, Roos D, Hartsell WF, Hoskin P, Wu JS, Nabid A, Tissing-Tan CJ, Oei B, Babington S, Demas WF, Wilson CF, Wong RK, Brundage M. Impact of reirradiation of painful osseous metastases on quality of life and function: a secondary analysis of the NCIC CTG SC.20 randomized trial. J Clin Oncol. 2014 Dec 1;32(34):3867-73. doi: 10.1200/JCO.2014.57.6264. Epub 2014 Oct 27.
Results Reference
derived

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Single vs Multiple-Fraction Therapy in Treating Patients With Previously Irradiated Painful Bone Metastases

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