Clinical trial NCT00080912: 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
Overall status: COMPLETED
Phase: NA
Conditions: Metastatic Cancer
Pain
Keywords: bone metastases
pain
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Radiation Therapy Oncology Group
name: Trans Tasman Radiation Oncology Group
name: Cancer Research UK
name: Assistance Publique - Hôpitaux de Paris
First posted: 2004-04-08
Enrollment: 850
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 ≥ 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

Primary outcomes:
measure: Pain Relief Measured by the Brief Pain Inventory at 2 Months After Treatment
timeFrame: 2 months
Secondary outcomes:
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Moncton
country: Canada
facility: The Vitalite Health Network - Dr. Leon Richard
state: New Brunswick
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston
state: Ontario
city: Kitchener
country: Canada
facility: Grand River Regional Cancer Centre
state: Ontario
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: McGill University - Dept. Oncology
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre hospitalier universitaire de Sherbrooke
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Toronto Sunnybrook Regional Cancer Centre
name: Edward LW Chow, MD
role: STUDY_CHAIR
affiliation: Advocate Good Samaratin Cancer Centre
name: William F. Hartsell, MD
role: STUDY_CHAIR
affiliation: Royal Adelaide Hospital Cancer Centre
name: Daniel Roos, MD
role: STUDY_CHAIR
affiliation: Radiotherapeutic Institution Friesland
name: Yvette von der Linden
role: STUDY_CHAIR
affiliation: Mount Vernon Cancer Centre
name: Peter Hoskin
role: STUDY_CHAIR
References:
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.
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.
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.
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.