Clinical trial NCT01248585: Dexamethasone vs Placebo in the Prophylaxis of Radiation-Induced Pain Flare Following Palliative Radiotherapy for Bone Metastases
Official title: A Randomized Phase III Double-Blind Study of Dexamethasone Versus Placebo in the Prophylaxis of Radiation-Induced Pain Flare Following Palliative Radiotherapy for Bone Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bone Metastases
Keywords: Symptom Control
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2010-11-25
Enrollment: 298
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: 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.

Detailed description: Previous research has shown that for patients who receive radiation therapy to treat their painful bone metastases, about 2 out of every 5 patients (about 40%) experience pain flare. The purpose of this study is to find out whether pain flare is prevented by receiving 8mg dexamethasone at least one hour prior to radiotherapy and once daily for the following 4 days. To do this, half of the patients in this study will get dexamethasone and the other half will receive a placebo (a substance that does not do anything). Using a placebo is the best way to see if a new therapy is effective and to clearly see the potential side effects and impact on quality of life.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Plans to receive cytotoxic chemotherapy or systemic steroids during the on-study period (day of study radiotherapy and the subsequent ten days).
* Plans to start or stop systemic therapy other than cytotoxic chemotherapy (e.g. hormonal therapy; immunotherapy; bisphosphonates) during the on-study period (day of study radiotherapy and the subsequent ten days). Patients who are already receiving these types of treatments are eligible as long as no changes are planned during the study period.
* Regular use of a non-steroidal anti-inflammatory drug (NSAID). Patients must not be taking NSAIDs at randomization and their use during the on-study period (day of study radiotherapy and the subsequent ten days) must not be required or expected. Patients who use daily low-dose ASA for anti-platelet therapy are eligible if ASA has been used for more than one month prior to the time of randomization.
* Plans for a change in analgesic regimen on the day of randomization.
* Previous entry on the SC.23 study.

Primary outcomes:
measure: Radiation-induced Pain Flare Incidence
timeFrame: 10 days
Secondary outcomes:
measure: Radiation-induced Pain Flare Incidence From Day 6 to Day 10 After Radiotherapy Treatment
timeFrame: From Day 6 to day 10 after radiotherapy treatment
measure: Analgesic Use
timeFrame: 10 days
measure: Response to Radiation Treatment at Six Weeks
timeFrame: From day 0 to 6 weeks
measure: Change in Pain Intensity Score Over 10 Days After Radiotherapy.
timeFrame: Pain intensity score change from baseline of day 0 to day 10 after radiation
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Abbotsford
country: Canada
facility: BCCA - Abbotsford Centre
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Victoria
country: Canada
facility: BCCA - Vancouver Island Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Moncton
country: Canada
facility: The Vitalite Health Network - Dr. Leon Richard
state: New Brunswick
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
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: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Newmarket
country: Canada
facility: Stronach Regional Health Centre at Southlake
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
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: Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Quebec City
country: Canada
facility: CHUQ-Pavillon Hotel-Dieu de Quebec
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
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto ON
name: Edward LW Chow
role: STUDY_CHAIR
affiliation: Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto ON
name: Carlo De Angelis
role: STUDY_CHAIR
affiliation: Cross Cancer Institute, Edmonton AB
name: Alysa Fairchild
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.