RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether single-fraction (single-dose) radiation therapy is more effective than multiple-fraction reirradiation (many small doses of radiation therapy) in relieving bone pain caused by bone metastases.

PURPOSE: Randomized phase III trial to compare the effectiveness of single-dose radiation therapy with that of multiple-dose radiation therapy in treating patients who have painful bone metastases.

Condition	Treatment or Intervention	Phase
bone metastases Pain	Procedure: pain therapy  Procedure: radiation therapy  Procedure: supportive care/therapy	Phase III

OBJECTIVES: Primary

• Compare pain relief in patients undergoing single-fraction vs multiple-fraction re-irradiation of painful bone metastases.

Secondary

• Compare overall pain relief in patients treated with these regimens.
• Compare time to pain progression in patients treated with these regimens.
• Correlate initial irradiation response with 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 and the Netherlands only).
• Compare characteristics of non-responders (to both initial and re-irradiation) among patients treated with these regimens.
• Compare the incidence of acute severe radiation-related side effects in patients treated with these regimens.
• Compare 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 on day 1.
• Arm II: Patients receive multiple-fraction radiotherapy once daily on days 1-5 or on days 1-8 if re-irradiation of the spine and/or whole pelvis is involved. At least 4 weeks after the first re-treatment, patients in both arms may receive a second re-treatment in the absence of unacceptable pain progression or unacceptable toxicity.

Patients complete a Brief Pain Inventory questionnaire on days 7 and 14, monthly during months 1-6, and at months 9 and 12. Quality of life is assessed at baseline and then monthly during months 1-6.

Patients are followed for up to 1 year.

PROJECTED ACCRUAL: A total of 650 patients (325 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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 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 site of pain for palliative radiotherapy must be smaller or similar in size to initial treatment field
• No clinical or radiological evidence of pathological fractures in extremities of the area to be re-irradiated
• No high-risk lytic lesion > 3 cm OR > 50% cortical erosion of bone diameter
• No clinical or radiological evidence of spinal cord compression
• Ineligible for surgical intervention

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, or Dutch
• Must be accessible for treatment follow-up

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
• 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 prior 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

Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada; Recruiting
      Tom Baker Cancer Centre - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada; Recruiting
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada; Recruiting
Canada, New Brunswick
      Saint John Regional Hospital, Saint John,  New Brunswick,  E2L 4L2,  Canada; Recruiting
Canada, Newfoundland and Labrador
      Newfoundland Cancer Treatment and Research Foundation, St. Johns,  Newfoundland and Labrador,  A1B 3V6,  Canada; Recruiting
Canada, Nova Scotia
      Nova Scotia Cancer Centre, Halifax,  Nova Scotia,  B3H 1V7,  Canada; Recruiting
Canada, Ontario
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada; Recruiting
      Durham Regional Cancer Centre at Lakeridge Health Oshawa, Oshawa,  Ontario,  L1G 2B9,  Canada; Recruiting
      Kingston Regional Cancer Centre, Kingston,  Ontario,  K7L 5P9,  Canada; Recruiting
      Margaret and Charles Juravinski Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada; Recruiting
      Ottawa Regional Cancer Centre, Ottawa,  Ontario,  K1H 1C4,  Canada; Recruiting
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada; Recruiting
      Regional Cancer Care at Thunder Bay Regional Health Sciences Centre, Thunder Bay,  Ontario,  P7B 6V4,  Canada; Recruiting
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada; Recruiting
Canada, Quebec
      CHUS-Hopital Fleurimont, Fleurimont,  Quebec,  J1H 5N4,  Canada; Recruiting
Netherlands
      Kennemer Gasthuis - Locatie EG, Haarlem,  2000,  Netherlands; Recruiting
United Kingdom, England
      Mount Vernon Hospital, Northwood,  England,  HA6 2RN,  United Kingdom; Recruiting

Study chairs or principal investigators

Edward L.W. Chow, MD,  Study Chair,  Toronto Sunnybrook Regional Cancer Centre   

Study ID Numbers:  CDR0000357423; CAN-NCIC-SC.20
Record last reviewed:  October 2004
Record first received:  April 7, 2004
ClinicalTrials.gov Identifier:  NCT00080912
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-18