Dexamethasone vs Placebo in the Prophylaxis of Radiation-Induced Pain Flare Following Palliative Radiotherapy for Bone Metastases
Condition: Bone Metastases
MeSH terms: Neoplasm Metastasis; Bone Neoplasms; Bone Marrow Diseases
Intervention: Dexamethasone; Placebo
Intervention description: 2 x 4 mg dexamethasone (dex) tablets taken once daily for 5 days; 2 placebo tablets taken once daily for 5 days
Intervention MeSH terms: Dexamethasone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 298.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Symptom Control

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.
    

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.