Bone MetastasesPhase 3NCT01669499
Dexamethasone for Pain Flare After Radiotherapy of Painful Bone metastasesZonMW 11510009
A Phase 3 study testing Dexamethasone acetate in people with Bone Metastases, run by UMC Utrecht at 2 sites in Netherlands.
Trial summary
Cancer patients with pain due to bone metastases are often treated with external irradiation in order to reduce pain. However, patients may experience a temporary increase of pain shortly after irradiation, a so-called pain flare. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bone Metastases
- What is being tested?
- Dexamethasone acetate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 411 participants
- Where
- 2 sitesNetherlands
- Study dates
- Jan 2012to Apr 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients of 18 years or older
- Uncomplicated painful bone metastases
- Primary malignancy is a solid tumour • Pain intensity on a numeric rating scale of 2-8
- No immediately expected change in the analgesic regimen.
- Indication for single or short course radiotherapy
- Able to fill out Dutch questionnaires
- Able to follow instructions
- Informed consent provided
Who cannot join
- Patients with hematological malignancy
- Multliple sites to be irradiated
- Patients who have been treated before with palliative radiotherapy for painful bone metastases
- Current use of steroids (dexamethasone, prednisolone or other), or use up to less than a week before randomization
- Long-term schedule radiotherapy (>6 fractions)
- Life expectancy shorter than 8 weeks
- Karnofsky Performance Score of 40 or less
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Leiden University Medical Centre
Leiden, South Holland, 2333 ZA
University Medical Center Utrecht
Utrecht, Utrecht, 3485 CX
About this study
Official title: Dexamethasone for the Prevention of a Pain Flare After Palliative Radiotherapy for Painful Bone Metastases: a Multi-center Double-blind Placebo-controlled Randomized Study
Cancer patients with pain due to bone metastases are often treated with external irradiation in order to reduce pain. However, patients may experience a temporary increase of pain shortly after irradiation, a so-called pain flare. This study investigates whether a short course of a drug called dexamethasone may prevent the occurrence of a pain flare. Patients, who are irradiated for painful bone metastases are randomized into three groups. Group 1 receives placebo during four days, group 2 receives dexamethasone on the day of the irradiation and placebo during three days, and group 3 receives dexamethasone during four days. All patients complete a questionnaire on pain, side-effects of treatment and quality of life during 14 days and after four weeks. This study will define whether dexamethasone decreases the occurrence of a pain flare after irradiation for painful bone metastases, and, if so, whether four days of treatment with dexamethasone is better dan one day of treatment.
Read the detailed description
Background of the study:
Patients with pain due to bone metastases are often treated with palliative short schedule external beam radiotherapy. Dependent on the institutional protocols, single fraction (8 Gy) or 5-6 fractions of 4 Gy are usually applied. Randomized studies have shown the equal effectiveness of both schedules in treating pain, with almost 70% of patients experiencing less or no pain within three to four weeks after treatment (Wu 2003). However, within 10 days after treatment a short term transient progression of pain may occur, the so-called pain flare (Chow 2005, Loblaw 2007, Hird 2009-1). Two prospective observational studies reported patient-based daily pain scores after radiotherapy for painful bone metastases. Loblaw showed a pain flare in 44% patients after 8 Gy and in 24% patients after 20 Gy in 4 fractions (Loblaw 2007). The median duration of the pain flare was three days. A recent publication found no difference in pain flare in 111 patients after single vs. multiple fractions (39% vs. 41%, resp.) (Hird 2009-1). No data are available of the occurrence of pain flare in Dutch patients. The largest trial to date on painful bone metastases, the Dutch Bone Metastasis Study, was funded by OG and CKTO and randomized from 1996-1998 a total of 1157 patients between 8 Gy single fraction and 24 Gy in 6 fractions (PhD thesis, van der Linden 2005). Follow-up consisted of 12 weekly and thereafter monthly questionnaires on pain, pain medication and quality of life. In this study, daily scoring of pain to asses pain flare was not performed. When a pain flare occurs oral dexamethasone can be prescribed. The rationale for administering steroids is to decrease edema that arises in the periostium of the affected bone shortly after radiotherapy and thereby to reduce pain (de Graeff 2006). Two small studies were performed to study the effectiveness of dexamethasone for treating a pain flare (Chow 2007, Hird 2009-2). Chow et al. administered 8 mg dexamethasone to 23 patients one hour before single fraction treatment and showed pain flare in only 24% of patients (95% CI 10-39%) within the first 10 days after radiotherapy (Chow 2007). Only one patient had a flare within two days after treatment. Dexamethasone was well tolerated. In a fase 2 study of the same research group 41 patients were administered 8 mg dexamethasone before and then for three consecutive days after single fraction treatment. They showed a pain flare in 22% of patients (with a median duration of one day), with 81% occurring within five days after treatment, and 95% within 10 days (Hird 2009-2). Both studies concluded that randomized studies are necessary to collect unbiased data on the occurrence and duration of pain flare and the effectiveness of drug treatment. Until now, no randomized studies were performed comparing dexamethasone with placebo or no treatment. The effectiveness of placebo vs. dexamethasone in the treatment of pain flare in patients after radiotherapy for painful bone metastases is the subject of this study.
Aim of the study To study the effectiveness and toxicity of dexamethasone to prevent the occurrence of a pain flare after short schedule radiotherapy for painful bone metastases and to define the optimal schedule of dosing.
Research questions:
- What is the effectiveness of dexamethasone to prevent the occurrence of a pain flare after short schedule radiotherapy for painful bone metastases?
- Is there a difference in effectiveness between a single dose of 8 mg dexamethasone before radiotherapy or a dose of 8 mg dexamethasone before radiotherapy in combination with three additional doses during the three following days?
- What are the side effects of dexamethasone and placebo in patients treated with radiotherapy for painful bone metastases? 4. Does a pain flare predict for pain response to radiotherapy?
Study design:
This study is a randomized, controlled, multicenter study in 411 patients with painful bone metastases who are referred for a short course of palliative radiotherapy. Short course radiotherapy encompasses all treatment schedules from one to six fractions of radiotherapy. The study consists of three arms:
- Arm 1: day 0: placebo, day 1, 2 en 3: placebo
- Arm 2: day 0: 8 mg dexamethasone, day 1, 2 en 3: placebo
- Arm 3: day 0: 8 mg dexamethasone, day 1, 2 en 3: 8 mg dexamethasone Day 0 is the first day of radiotherapy treatment. On day 0 the tablet of placebo or dexamethasone will be administered one hour before radiotherapy. On day 1, 2, and 3 the tablet of placebo or dexamethasone will be taken in the morning at about 8 a.m.
- Conditions
- Bone Metastases
- Being tested
- Dexamethasone acetate, Placebo
- Keywords
- Bone metastases, radiotherapy, dexamethasone, pain flare
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dexamethasone acetateDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo on day 0-3 Receives: Drug: Placebo |
| Dexamethasone acetate day 0 | Active comparator | 8 mg dexamethasone on day 0 Receives: Drug: Dexamethasone acetate; Drug: Placebo |
| Dexamethasone acetate day 0-3 | Active comparator | 8 mg dexamethasone on day 0-3 Receives: Drug: Dexamethasone acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
The occurrence of a pain flare.
A pain flare is defined by a two-point increase after radiotherapy of the worst pain score on Pain flare is defined as an 11-point scale of 0 (no pain) to 10 (worst imaginable pain) compared to baseline without a decrease in analgesic intake, or a 25% increase in analgesic intake without decrease in worst pain score (according to international bone metastases consensus guidelines) (Chow 2007).
Measured: Within 2 weeks after irradiation
Secondary outcomes (3)
Pain scores
Pain scores as measured by BPI
Measured: Days 1-14 and 28
Quality of life
As measured by the quality of life scale of the EORTC PAL15
Measured: Days 7, 14 and 28
Side effects
As measured by questionnaire
Measured: Day 1-14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2012 (estimated)
- Study startJan 2012
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bone MetastasesStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 411 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Principal investigator, A. de Graeff, UMC Utrecht
- Investigators
- Alexander de Graeff, MD, PhD, Principal investigator, Medical Oncologist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01669499
- Sponsor's protocol ID
- ZonMW 11510009
- Status last verified
- Nov 2016
- First submitted
- 16 Aug 2012
- Last updated
- 16 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Westhoff PG, de Graeff A, Geerling JI, Reyners AK, van der Linden YM. Dexamethasone for the prevention of a pain flare after palliative radiotherapy for painful bone metastases: a multicenter double-blind placebo-controlled randomized trial. BMC Cancer. 2014 May 20;14:347. doi: 10.1186/1471-2407-14-347.
PubMed 24885354
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dexamethasone for the Prevention of a Pain Flare After Palliative Radiotherapy for Painful Bone Metastases: a Multi-center Double-blind Placebo-controlled Randomized Study
- ClinicalTrials.gov ID
- NCT01669499
- Acronym / sponsor ID
- ZonMW 11510009
- Conditions
- Bone Metastases
- Keywords
- Bone metastases, radiotherapy, dexamethasone, pain flare
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 411 participants (estimated)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- Jan 2012
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 21 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cancer patients with pain due to bone metastases are often treated with external irradiation in order to reduce pain. However, patients may experience a temporary increase of pain shortly after irradiation, a so-called pain flare. This study investigates whether a short course of a drug called dexamethasone may prevent the occurrence of a pain flare. Patients, who are irradiated for painful bone metastases are randomized into three groups. Group 1 receives placebo during four days, group 2 receives dexamethasone on the day of the irradiation and placebo during three days, and group 3 receives dexamethasone during four days. All patients complete a questionnaire on pain, side-effects of treatment and quality of life during 14 days and after four weeks. This study will define whether dexamethasone decreases the occurrence of a pain flare after irradiation for painful bone metastases, and, if so, whether four days of treatment with dexamethasone is better dan one day of treatment.
Detailed description
Background of the study:
Patients with pain due to bone metastases are often treated with palliative short schedule external beam radiotherapy. Dependent on the institutional protocols, single fraction (8 Gy) or 5-6 fractions of 4 Gy are usually applied. Randomized studies have shown the equal effectiveness of both schedules in treating pain, with almost 70% of patients experiencing less or no pain within three to four weeks after treatment (Wu 2003). However, within 10 days after treatment a short term transient progression of pain may occur, the so-called pain flare (Chow 2005, Loblaw 2007, Hird 2009-1). Two prospective observational studies reported patient-based daily pain scores after radiotherapy for painful bone metastases. Loblaw showed a pain flare in 44% patients after 8 Gy and in 24% patients after 20 Gy in 4 fractions (Loblaw 2007). The median duration of the pain flare was three days. A recent publication found no difference in pain flare in 111 patients after single vs. multiple fractions (39% vs. 41%, resp.) (Hird 2009-1). No data are available of the occurrence of pain flare in Dutch patients. The largest trial to date on painful bone metastases, the Dutch Bone Metastasis Study, was funded by OG and CKTO and randomized from 1996-1998 a total of 1157 patients between 8 Gy single fraction and 24 Gy in 6 fractions (PhD thesis, van der Linden 2005). Follow-up consisted of 12 weekly and thereafter monthly questionnaires on pain, pain medication and quality of life. In this study, daily scoring of pain to asses pain flare was not performed. When a pain flare occurs oral dexamethasone can be prescribed. The rationale for administering steroids is to decrease edema that arises in the periostium of the affected bone shortly after radiotherapy and thereby to reduce pain (de Graeff 2006). Two small studies were performed to study the effectiveness of dexamethasone for treating a pain flare (Chow 2007, Hird 2009-2). Chow et al. administered 8 mg dexamethasone to 23 patients one hour before single fraction treatment and showed pain flare in only 24% of patients (95% CI 10-39%) within the first 10 days after radiotherapy (Chow 2007). Only one patient had a flare within two days after treatment. Dexamethasone was well tolerated. In a fase 2 study of the same research group 41 patients were administered 8 mg dexamethasone before and then for three consecutive days after single fraction treatment. They showed a pain flare in 22% of patients (with a median duration of one day), with 81% occurring within five days after treatment, and 95% within 10 days (Hird 2009-2). Both studies concluded that randomized studies are necessary to collect unbiased data on the occurrence and duration of pain flare and the effectiveness of drug treatment. Until now, no randomized studies were performed comparing dexamethasone with placebo or no treatment. The effectiveness of placebo vs. dexamethasone in the treatment of pain flare in patients after radiotherapy for painful bone metastases is the subject of this study.
Aim of the study To study the effectiveness and toxicity of dexamethasone to prevent the occurrence of a pain flare after short schedule radiotherapy for painful bone metastases and to define the optimal schedule of dosing.
Research questions:
- What is the effectiveness of dexamethasone to prevent the occurrence of a pain flare after short schedule radiotherapy for painful bone metastases?
- Is there a difference in effectiveness between a single dose of 8 mg dexamethasone before radiotherapy or a dose of 8 mg dexamethasone before radiotherapy in combination with three additional doses during the three following days?
- What are the side effects of dexamethasone and placebo in patients treated with radiotherapy for painful bone metastases? 4. Does a pain flare predict for pain response to radiotherapy?
Study design:
This study is a randomized, controlled, multicenter study in 411 patients with painful bone metastases who are referred for a short course of palliative radiotherapy. Short course radiotherapy encompasses all treatment schedules from one to six fractions of radiotherapy. The study consists of three arms:
- Arm 1: day 0: placebo, day 1, 2 en 3: placebo
- Arm 2: day 0: 8 mg dexamethasone, day 1, 2 en 3: placebo
- Arm 3: day 0: 8 mg dexamethasone, day 1, 2 en 3: 8 mg dexamethasone Day 0 is the first day of radiotherapy treatment. On day 0 the tablet of placebo or dexamethasone will be administered one hour before radiotherapy. On day 1, 2, and 3 the tablet of placebo or dexamethasone will be taken in the morning at about 8 a.m.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo on day 0-3 |
| Dexamethasone acetate day 0 | Active comparator | Drug: Dexamethasone acetate, Drug: Placebo8 mg dexamethasone on day 0 |
| Dexamethasone acetate day 0-3 | Active comparator | Drug: Dexamethasone acetate8 mg dexamethasone on day 0-3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients of 18 years or older
- Uncomplicated painful bone metastases
- Primary malignancy is a solid tumour • Pain intensity on a numeric rating scale of 2-8
- No immediately expected change in the analgesic regimen.
- Indication for single or short course radiotherapy
Key exclusion criteria (7 listed)
- Patients with hematological malignancy
- Multliple sites to be irradiated
- Patients who have been treated before with palliative radiotherapy for painful bone metastases
- Current use of steroids (dexamethasone, prednisolone or other), or use up to less than a week before randomization
- Long-term schedule radiotherapy (>6 fractions)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dexamethasone acetate | Drug | Dexamethasone acetate day 0, Dexamethasone acetate day 0-3 |
| Placebo | Drug | Dexamethasone acetate day 0, Placebo |
Primary outcome
The occurrence of a pain flare.
Time frame: Within 2 weeks after irradiation
A pain flare is defined by a two-point increase after radiotherapy of the worst pain score on Pain flare is defined as an 11-point scale of 0 (no pain) to 10 (worst imaginable pain) compared to baseline without a decrease in analgesic intake, or a 25% increase in analgesic intake without decrease in worst pain score (according to international bone metastases consensus guidelines) (Chow 2007).
3 secondary outcomes
Pain scores
Time frame: Days 1-14 and 28
Quality of life
Time frame: Days 7, 14 and 28
Side effects
Time frame: Day 1-14
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2016.
- Derived from this study: PubMed 24885354Westhoff PG, de Graeff A, Geerling JI, Reyners AK, van der Linden YM. Dexamethasone for the prevention of a pain flare after palliative radiotherapy for painful bone metastases: a multicenter double-blind placebo-controlled randomized trial. BMC Cancer. 2014 May 20;14:347. doi: 10.1186/1471-2407-14-347.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexander de Graeff, MD, PhD principal investigator
Medical Oncologist
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dexamethasone acetate in people with Bone Metastases, run by UMC Utrecht at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The occurrence of a pain flare. (time frame: Within 2 weeks after irradiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01669499, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2016.