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

NCT ID: NCT00080912

Last Updated: 2023-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 850 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-22
• Study Completion Date: 2014-01-16

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.

Conditions

Metastatic Cancer; Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

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

Group Type: EXPERIMENTAL

radiation therapy

Intervention Type: RADIATION

Given in a single fraction or multiple fractions

Arm II

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.

Group Type: ACTIVE_COMPARATOR

radiation therapy

Intervention Type: RADIATION

Given in a single fraction or multiple fractions

Interventions

radiation therapy

Given in a single fraction or multiple fractions

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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 ≥ 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 ≥ 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: collaborator

Trans Tasman Radiation Oncology Group

OTHER

Sponsor Role: collaborator

Cancer Research UK

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edward LW Chow, MD

Role: STUDY_CHAIR

Toronto Sunnybrook Regional Cancer Centre

William F. Hartsell, MD

Role: STUDY_CHAIR

Advocate Good Samaratin Cancer Centre

Daniel Roos, MD

Role: STUDY_CHAIR

Royal Adelaide Hospital Cancer Centre

Yvette von der Linden

Role: STUDY_CHAIR

Radiotherapeutic Institution Friesland

Peter Hoskin

Role: STUDY_CHAIR

Mount Vernon Cancer Centre

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, Canada

Grand River Regional Cancer Centre

Kitchener, Ontario, Canada

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, Canada

Odette Cancer Centre

Toronto, Ontario, Canada

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

CHUM - Hopital Notre-Dame

Montreal, Quebec, Canada

McGill University - Dept. Oncology

Montreal, Quebec, Canada

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Countries

Canada

References

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.

Reference Type: BACKGROUND

PMID: 16523812 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24369114 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29102263 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25349296 (View on PubMed)

Other Identifiers

CAN-NCIC-SC20

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG-0433

Identifier Type: OTHER

Identifier Source: secondary_id

TROG-03.08

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000357423

Identifier Type: OTHER

Identifier Source: secondary_id

SC20

Identifier Type: -

Identifier Source: org_study_id

NCT00797173

Identifier Type: -

Identifier Source: nct_alias