Dexamethasone vs Placebo in the Prophylaxis of Radiation-Induced Pain Flare Following Palliative Radiotherapy for Bone Metastases

NCT01248585 | Completed Phase 3 Results DMC

• 1 other identifier: SC23
• Study Type: interventional
• Target: 298
• Locations: 1 country
• Sites: 22

Brief Summary

This research is being done because is is not known if dexamethasone can prevent pain flare (their pain temporarily gets worse before it gets better) caused by the radiation used to treat painful bone metastases. Using dexamethasone to prevent pain like this has been studied in a few people and seems promising, but it is not clear if it can decrease the pain or prevent the pain flare before it happens.

Conditions

Bone Metastases

Keywords

Symptom Control

Outcome Measures

Primary Outcomes (1)

• Radiation-induced Pain Flare Incidence

  The incidences of radiation-induced pain flare from the time of radiotherapy treatment to ten days after the completion of treatment

  10 days

Secondary Outcomes (4)

• Radiation-induced Pain Flare Incidence From Day 6 to Day 10 After Radiotherapy Treatment

  From Day 6 to day 10 after radiotherapy treatment

• Analgesic Use

  10 days

• Response to Radiation Treatment at Six Weeks

  From day 0 to 6 weeks

• Change in Pain Intensity Score Over 10 Days After Radiotherapy.

  Pain intensity score change from baseline of day 0 to day 10 after radiation

Study Arms (2)

Dexamethasone

ACTIVE COMPARATOR

2 x 4 mg dexamethasone tablets taken once daily for 5 days

Drug: Dexamethasone

Placebo

PLACEBO COMPARATOR

2 placebo tablets taken once daily for 5 days

Drug: Placebo

Interventions

Dexamethasone DRUG

2 x 4 mg dexamethasone (dex) tablets taken once daily for 5 days

Dexamethasone

Placebo DRUG

2 placebo tablets taken once daily for 5 days

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a histologically or cytologically proven malignancy. All non-hematologic malignant tumours of any histology are eligible.
• Be 18 years of age or older at the time of randomization.
• Have bone metastasis(es) corresponding to the clinically painful area(s) documented by radiological imaging within six months prior to randomization.
• Karnofsky Performance Status (KPS) must be ≥ 40 at the time of the baseline evaluation (within seven days prior to randomization). As it is difficult to obtain complete data from inpatients on a daily basis, they should not be randomized to this study.
• Is planned to receive palliative radiotherapy to one or two bony metastasis(es) with the treatment given as 8 Gy in a single fraction to all sites to be followed for the study. Although a maximum of two sites can be treated and followed for the study, patients with more than two skeletal metastases are eligible. At the time of delivery of study radiotherapy, only the site(s) being followed for the study may be treated.
• Is able to provide the worst pain score at the bony metastatic site(s) planned for palliative radiotherapy.
• Has a baseline worst pain score ≥ 2 on a scale of 0-10 at all the bony metastatic site(s) planned for palliative radiotherapy as part of this study within 7 days prior to randomization. If two painful sites will be followed for the study, this requirement must be met on the same day for both sites.
• Is able and willing to fill out the daily diary.
• Is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaire in either English or French. The baseline assessment must be completed within required timelines prior to randomization. Inability (illiteracy in English or French, 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.
• 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 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 but a sample form is provided. A copy of the initial full board REB approval and approved consent form must be sent to the central office. The patient must sign the consent form prior to randomization. Please note that the consent form for this study must contain a statement which gives permission for the NCIC CTG and monitoring agencies to review patient records.
• If being enrolled through a centre participating in the correlative science component of the study, is willing and able to provide a pre- and post-treatment urine sample. Language pertaining to patient consent for urine collection must be included in the consent form for the main study at these centres. The patient must sign this consent form prior to collection of the first urine sample.
• If being enrolled through a centre participating in the correlative science component of the study, patient consent for the saliva collection component of the trial must be obtained in the same manner as outlined above for the main study consent. The patient must sign the saliva collection Informed Consent form.
• Must be accessible for treatment and follow-up. Investigators must be reasonably assured that the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
• Protocol treatment is to begin within one week of patient randomization.

You may not qualify if:

• Patients with hematologic malignancies (leukemia, Hodgkin's or non-Hodgkin's lymphoma or plasma cell dyscrasia, including multiple myeloma) are ineligible as steroids constitute anti-cancer therapy for these malignancies.
• Concurrent use or use within previous seven days of any corticosteroid medication other than topical or inhaled preparations. Patients with any type of cancer who are receiving steroids as a component of their systemic therapy are ineligible. Patients requiring steroids for a co-existing medical problem are ineligible. Patients who received a one- to three-day dose of steroids as an antiemetic for chemotherapy treatment are eligible, as long as at least 72 hours have elapsed since the last dose of antiemetic therapy.
• Medical contraindications to corticosteroids such as uncontrolled diabetes mellitus, uncontrolled hypertension, active peptic ulcer or hypokalemia.
• Uncorrected hypokalemia that is known to exist within 7 days prior to randomization. Patients with previous hypokalemia that has been corrected are eligible. Hypokalemia is defined as a potassium level \< 3.0 mmol/L. Testing of electrolytes, including potassium level, is not a protocol requirement.
• Random glucose level ≥ 13.9 mmol/L within 7 days prior to randomization.Testing of glucose within 7 days prior to randomization is a protocol requirement. Point of care testing with a glucometer is permissible.
• Pathological fracture of the femora, tibiae, fibulae, humeri, radii or ulnae at the site(s) to be followed for the study.
• Radiological evidence of high-risk lesions for pathological fractures in the femora, tibiae, fibulae, humeri, radii or ulnae at the site(s) to be followed for the study (lytic lesions \> 3 cm or \> 50% cortical erosion of bone diameter).
• Clinical or available radiologic evidence of spinal cord or cauda equina compression at the site(s) to be followed for the study.
• Plans to receive palliative radiotherapy to a site or sites other than the one(s) being followed for the study during the ten-day period following study radiotherapy.
• Planned orthopedic intervention, including kyphoplasty, vertebroplasty or cementoplasty, to any of the site(s) to be followed for the study.
• Prior palliative surgery to any of the site(s) to be followed for the study.
• Inability, with available translator assistance, to record pain score and medication consumption in the daily diary and to communicate this to study personnel.
• Receipt of radiopharmaceutical treatment at any time.
• Previous external beam radiotherapy (including hemibody radiotherapy) using a field that included the site(s) to be followed for the study.
• Inability to swallow or tolerate oral medications, e.g. due to intractable nausea and/or emesis.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead

Study Sites (22)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Abbotsford Centre

Abbotsford, British Columbia, V2S 0C2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, V8R 6V5, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, E1C 8X3, Canada

Location

Royal Victoria Regional Health Centre

Barrie, Ontario, L4M 6M2, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

Grand River Regional Cancer Centre

Kitchener, Ontario, N2G 1G3, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Stronach Regional Health Centre at Southlake

Newmarket, Ontario, L3Y 2P9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (4)

• Chow E, Meyer RM, Ding K, Nabid A, Chabot P, Wong P, Ahmed S, Kuk J, Dar AR, Mahmud A, Fairchild A, Wilson CF, Wu JSY, Dennis K, Brundage M, DeAngelis C, Wong RKS. Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1463-1472. doi: 10.1016/S1470-2045(15)00199-0. Epub 2015 Oct 18.

  PMID: 26489389 RESULT

• Chow S, Ding K, Wan BA, Brundage M, Meyer RM, Nabid A, Chabot P, Coulombe G, Ahmed S, Kuk J, Dar AR, Mahmud A, Fairchild A, Wilson CF, Wu JSY, Dennis K, DeAngelis C, Wong RKS, Zhu L, Chow E. Gender differences in pain and patient reported outcomes: a secondary analysis of the NCIC CTG SC. 23 randomized trial. Ann Palliat Med. 2017 Dec;6(Suppl 2):S185-S194. doi: 10.21037/apm.2017.08.12. Epub 2017 Aug 29.

  PMID: 29156903 DERIVED

• McDonald R, Ding K, Brundage M, Meyer RM, Nabid A, Chabot P, Coulombe G, Ahmed S, Kuk J, Dar AR, Mahmud A, Fairchild A, Wilson CF, Wu JSY, Dennis K, DeAngelis C, Wong RKS, Zhu L, Chan S, Chow E. Effect of Radiotherapy on Painful Bone Metastases: A Secondary Analysis of the NCIC Clinical Trials Group Symptom Control Trial SC.23. JAMA Oncol. 2017 Jul 1;3(7):953-959. doi: 10.1001/jamaoncol.2016.6770.

  PMID: 28196208 DERIVED

• Raman S, Ding K, Chow E, Meyer RM, Nabid A, Chabot P, Coulombe G, Ahmed S, Kuk J, Dar AR, Mahmud A, Fairchild A, Wilson CF, Wu JSY, Dennis K, DeAngelis C, Wong RKS, Zhu L, Brundage M. Minimal clinically important differences in the EORTC QLQ-BM22 and EORTC QLQ-C15-PAL modules in patients with bone metastases undergoing palliative radiotherapy. Qual Life Res. 2016 Oct;25(10):2535-2541. doi: 10.1007/s11136-016-1308-4. Epub 2016 May 2.

  PMID: 27138964 DERIVED

MeSH Terms

Interventions

Dexamethasone; Sugars

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Carbohydrates

Results Point of Contact

• Title: Keyue Ding, Biostatistician
• Organization: Canadian Cancer Trials Group

kding@ctg.queensu.ca

613-533-6430

Study Officials

• Edward LW Chow

  Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto ON

  STUDY CHAIR

• Carlo De Angelis

  Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto ON

  STUDY CHAIR

• Alysa Fairchild

  Cross Cancer Institute, Edmonton AB

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2010
• First Posted: November 25, 2010
• Study Start: May 30, 2011
• Primary Completion: May 25, 2015
• Study Completion: November 27, 2015
• Last Updated: August 28, 2023
• Results First Posted: October 22, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (22)