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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase III International Randomized Trial Of Single Versus Multiple Fractions For Re-Irradiation Of Painful Bone Metastases

Conditions
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Metastatic Cancer, Pain

Intervention / Treatment
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* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive single-fraction radiotherapy (8 Gy) on day 1. | Radiation: radiation therapy<br>* Given in a single fraction or multiple fractions<br>|
| Active Comparator: Arm II<br>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. | Radiation: radiation therapy<br>* Given in a single fraction or multiple fractions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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%. | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone metastases, pain