Condition category
Cancer
Date applied
19/12/2005
Date assigned
19/12/2005
Last edited
21/03/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Y.M. Linden, van der

ORCID ID

Contact details

Radiotherapy Institute Friesland (RIF)
Borniastraat 36
Leeuwarden
8934 AD
Netherlands
+31 (0)58 2866667
y.m.linden@skf-rif.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00080912

Protocol/serial number

SC.20 / CKTO 2004-06

Study information

Scientific title

A phase III international randomised trial of single versus multiple fractions for re-irradiation of painful bone metastases

Acronym

METRET (METastases RETreatment)

Study hypothesis

Radiotherapy is an established treatment for painful bone metastases. Most patients in the United Kingdom will receive a single dose of 6 to 8 Gy although fractionated schedules are sometimes still employed. Many patients, particularly those with breast, prostate and renal cancer have a good initial response but later have pain recurrence and may be offered further radiotherapy. Additionally, it has been shown that some patients who fail to respond initially may benefit from re-irradiation. There is no data to inform the optimal radiotherapy schedule for retreatment.

The primary objective of this trial is to compare the efficacy of pain relief after re-irradiation with an 8 Gy single fraction or 20 Gy in five (or eight) fractions in a simple pragmatic two-arm randomised trial. Pain will be measured using the Wisconsin Brief Pain Inventory, which will be sent to patients at intervals by the trials centre.

Secondary objectives include determining the overall incidence of pain relief, studying the relationship between pain relief after re-irradiation and response to previous irradiation, as well as determining the characteristics of the group of non-responders (to both the first and second radiation), and the monitoring or acute severe adverse effects.

Ethics approval

Ethics approval received from the local medical ethics committee

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Bone metastases, malignancy

Intervention

ARM one: 8 Gy (single) one fraction
ARM two: 20 Gy (multiple) five or eight fractions (for spine and/or whole pelvis only)

Patients will be stratified by:
1. Their response to initial radiation as per physician's interpretation of patient history at the time of randomization into responders versus non-responders (i.e. patients who did or did not gain pain improvement after initial radiation)
2. Initial fractionation i.e. single 6-8 Gy versus multiple fractions (20-24 Gy/5-6# and 30 Gy/10#)
3. Centre

Intervention type

Other

Phase

Phase III

Drug names

Primary outcome measures

To compare pain relief after re-irradiation of symptomatic bone metastases with 8 Gy or 20 Gy

Secondary outcome measures

1. To determine the overall incidence of pain relief in patients undergoing re-irradiation for symptomatic bone metastases
2. To determine the time to pain progression after re-irradiation
3. To assess the relationship between response to initial radiation and pain relief with re-irradiation
4. To determine the changes in functional interference following re-irradiation using the Brief Pain Inventory (and quality of life [QoL] using EORTC QLQ C30 in Canada and the Netherlands)
5. To determine the characteristics of the group of non-responders (to both the initial and re irradiation)
6. To monitor the incidence of acute severe radiation-related side effects
7. To monitor the incidence of in-field pathological fractures and spinal cord compression

Overall trial start date

01/04/2005

Overall trial end date

01/04/2007

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patient must be 18 years of age or older at the time of randomisation
2. Patient must have histologically or cytologically proven malignancy
3. Histological diagnosis may be established from needle biopsy, bone marrow biopsy, cytology, or a surgical biopsy or resection
4. All malignant histologies/cytologies are eligible
5. Plain radiographs, radionuclide bone scans, Computed Tomography (CT) scans and/or magnetic resonance imaging confirm the presence of bone metastases corresponding to clinically painful area
6. Patient has a worst pain score of more than or equal to 2/10 as reported using the Brief Pain Inventory
7. There is no plan to make an immediate change in the analgesic regimen
8. Karnofsky Performance Status more than 50 within one week prior to randomisation
9. The interval between the last fraction of the initial radiation and the date of randomisation in this study is more than four weeks
10. Initial radiation treatment field is reproducible for re-irradiation
11. Pain is arising from the previously irradiated metastasis(es) and not from progressive disease in the adjoining or remote areas
12. Site of pain considered for palliative radiotherapy must be encompassed by the same or smaller treatment field/portal as initial treatment
13. Canada and The Netherlands only:
13.1. Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaire in English, French or Dutch. The baseline assessment must already have been completed
13.2. Inability (illiteracy in English, French or Dutch, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible
14. Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements. It will be the responsibility of the local participating investigators to obtain the necessary local clearance, and to indicate in writing to the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Study Coordinator that such clearance has been obtained, before the trial can commence in that centre. Because of differing requirements, a standard consent form for the trial will not be provided. A copy of the initial full board Research Ethics Board (REB) approval and approved consent form must be sent to the central office:
14.1. The patient must sign the consent form prior to randomisation or registration
14.2. The consent form for this study must contain a statement which gives permission for the NCIC CTG and monitoring agencies to review patient records
15. Patients must be accessible for treatment and follow-up. Investigators must assure themselves that the patients randomised on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
16. In accordance with NCIC CTG policy, treatment must begin within four weeks of randomisation

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

850

Participant exclusion criteria

1. Clinical or radiological evidence of spinal cord compression at the time of assessment for this study
2. Clinical or radiological evidence of pathological fractures of extremities in the area to be re-irradiated
3. Radiological evidence of high-risk lesions for pathological fractures in the extremities (lytic lesions more than 3 cm or more than 50% cortical erosion of bone diameter) and candidate for surgical intervention. Patients who are NOT surgical candidates are eligible for this study.
4. The treatment area has received prior palliative surgery
5. There is planned surgical intervention on the treated bone
6. Treatment field of initial radiation volume has to be enlarged/modified to accommodate symptomatic disease not previously irradiated, or to provide adequate treatment margin
7. Systemic radiotherapy (Sr-89) has been received within 30 days prior to randomisation
8. Patient has received half body irradiation including the current re-irradiation field within 30 days prior to randomisation

Recruitment start date

01/04/2005

Recruitment end date

01/04/2007

Locations

Countries of recruitment

Netherlands

Trial participating centre

Radiotherapy Institute Friesland (RIF)
Leeuwarden
8934 AD
Netherlands

Sponsor information

Organisation

Radiotherapy Institute Friesland (RIF) (The Netherlands)

Sponsor details

Borniastraat 36
Leeuwarden
8934 AD
Netherlands

Sponsor type

Not defined

Website

Funders

Funder type

Research organisation

Funder name

Trans-Tasman Radiation Oncology Group (TROG) (Australia/New Zealand)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Commissie voor Klinisch Toegepast Onderzoek (CKTO) (Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

National Cancer Institute of Canada (NCIC) (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Radiation Therapy Oncology Group (RTOG) (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

See https://clinicaltrials.gov/ct2/show/results/NCT00080912

Publication summary

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24369114

Publication citations

  1. Results

    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, 15, 2, 164-171, doi: 10.1016/S1470-2045(13)70556-4.

Additional files

Editorial Notes

21/03/2016: added link to results - basic reporting. On 15/02/2011 the following changes were made to this trial record: 1. The overall trial end date was changed from 01/04/2007 to 03/09/2010. 2. The target number of participants was changed from 650 to 850.