Bone MetastasesEXPLORENCT04109937
External Beam Radiation Therapy Post Surgery in Patients With Lower Extremity Bone Metastases Randomized Efficacy Trial
A study testing External beam radiation therapy in people with Bone Metastases and Lower Extremity Fracture, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
The objective of the present study is to evaluate the effectiveness of post-operative radiation therapy in lower extremity bone metastases. This trial will compare the health outcomes of patients receiving radiation therapy after Orthopaedic surgery to patients who will not receive radiation therapy post-surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bone Metastases, Lower Extremity Fracture, Pathological Fracture
- What is being tested?
- External beam radiation therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2020to Oct 2026
- Phase
- Interventional
- 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
- Is the patient 18 years of age or older at the time of randomization?
- Does the patient have histologically or cytologically proven malignancy?
- Does the patient have imaging confirming presence of bone metastases corresponding to clinically painful area?
- Does the patient have established bone metastatic pathological fracture(s) lower extremity OR has impending pathological fracture(s)?
- Does patient have KPS ≥40 with estimated survival of ≥ 6 months?
- Was informed consent obtained?
Who cannot join
- Did the patient have a prior impending or prior pathological fracture to the site and was previously fixed with orthopaedic surgery?
- Did the patient receive prior radiation to the site (external beam or stereotactic body radiation)?
- Did the patient have a radio-resistant tumor (renal cell carcinoma or melanoma)?
- Did the patient plan for radical resection of the bone metastases?
- Did the patient receive or is planning to receive other intra-operative tumor ablative therapies?
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase III Multicenter Randomized Trial Assessing the Efficacy of Post-Operative Conventional External Beam Radiation Therapy Following Orthopaedic Surgery in Patients With Lower Extremity Bone Metastases
The objective of the present study is to evaluate the effectiveness of post-operative radiation therapy in lower extremity bone metastases. This trial will compare the health outcomes of patients receiving radiation therapy after Orthopaedic surgery to patients who will not receive radiation therapy post-surgery. The primary objective of the study is to compare the need for a subsequent surgery at the same treatment site within 12 months of the initial surgery. Additionally, the need for radiation or re-irradiation, functional status, performance status, pain scores, radiologically detected local disease progression, and overall length of survival will be compared at clinical endpoints for the two study arms. It is hypothesized that those randomized to receive post-operative radiation therapy will less likely need a subsequent surgery within the 12 months after the primary surgical intervention. This may optimize the quality of life for this patient population.
Read the detailed description
The incidence of bone metastases in advanced cancer patients is substantial, representing 70% of all metastatic sites. Approximately 5-10% of all patients with bone metastases develop pathological fractures. Surgical reconstruction can be helpful following fracture or prophylactically in cases of an impending fracture. In these cases, post-operative radiation is the current clinical practice in North America and many countries around the world. Post-operative radiation has the potential to support bone healing and prevent tumor progression while also decreasing the need for subsequent orthopaedic surgeries to the same site. A recent systematic review, however, challenged the evidence on its efficacy and adoption as standard of care in this patient population. As well, post-operative radiation requires additional visits to the radiation centre (associated with added costs and efforts for both the patients and the healthcare system). There is also a "pain flare" phenomenon, in which up to 40% of patients receiving radiation for palliative bone metastases experience pain within 1-5 days following radiation. The pain can last for 10 days and may acutely mask potential clinical benefits of radiation.
Given that there is potential negative impact to these patients who are palliative with a relatively short lifespan, it is important that the efficacy of post-operative radiation is rigorously evaluated.
We propose a multicenter randomized controlled trial to assess the efficacy of post-operative radiation following orthopaedic surgery in patients with lower extremity bone metastases. 300 patients with pending or established lower extremity pathological fracture will be recruited to a trial of surgery alone vs. surgery with post-operative radiation. The primary endpoint is a second surgery to the same site within 12 months. Secondary outcomes include quality of life, pain and functional outcome markers, radiation or re-irradiation as applicable, a second surgery within 24 months for those patients alive, overall survival and cost effectiveness.
- Being tested
- External beam radiation therapy
- Medical subject headings
- Fractures, Spontaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
External beam radiation therapyRadiation
The post-operative radiation will cover entire prosthesis/surgical fixation device and will consist of the dose fractionation of: 20 Gy in 5 fractions or 30 Gy in 10 fractions.
| Study group | Role | What they receive |
|---|---|---|
| Surgery Alone | No intervention | Patients with lower extremity bone metastases will receive surgical fixation/reconstruction but will not receive any post-operative radiation therapy. |
| Surgery and Post-Operative Radiation Therapy | Active comparator | Patients with lower extremity bone metastases will receive surgical fixation/reconstruction and will receive any post-operative radiation therapy. Receives: Radiation: External beam radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subsequent surgery after primary surgery
Requirement of a subsequent surgery
Measured: 12 months following the date of primary surgery
Secondary outcomes (8)
Re-irradiation/radiation
Requirement for re-irradiation in arm 2 or radiation in arm 1
Measured: Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Subsequent surgery (between 13 months and 24 months)
Requirement of subsequent surgery past 12 months (between 13 months and 24 months)
Measured: Between 13 months and 24 months following date of primary surgery
Post-operative functional status and Karnofsky Performance Status (KPS)
The best, median, and worst post-operative functional status and KPS will be derived for each patient, and the Wilcoxin rank sum test will be used to compare the difference between treatment arms
Measured: Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Post-operative pain and analgesic use
The lowest, median, and worst post-operative pain score will be derived for each patient, and the Wilcoxin rank sum test will be used to compare the difference between treatment arms. The cumulative and mean of analgesic use will presented by treatment arm.
Measured: Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Radiologically determined local progression
Time to radiological local disease progression is defined as the time from randomization to the date of documented radiological logical disease progression or death whichever comes first.
Measured: Months 3, 6, 12, 18, and 24
Quality of life through functional ability
Quality of life measured measured using EORTC quality of life questionnaire (QLQ)-C15-Pal and EORTC quality of life questionnaire (QLQ)-BM22. This questionnaire includes for multi-item scales and six individual items. All items were scaled from 1 (not at all) to 4 (very much) in which a higher score indicates greater distress in symptom scales while a higher score in functional scale indicates greater functional ability. The EORTC QLQ-BM22 is a 22-item module that addresses disease symptoms related to bone metastasis. It has four subscales (painful sites, pain characteristics, functional interference and psychosocial aspects). All items were scaled from 1 (not at all) to 4 (very much), in which a higher score indicates greater distress in symptom scales while a higher score in functional scale indicates greater functional ability
Measured: Day of randomization, weeks 2 and 6, months 3, 6, 12, 18, and 24
Overall survival
Overall survival is defined as the time from randomization to the date of death from any cause, or censored at their last known alive data before or on data cutoff date
Measured: Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Cost-effectiveness
Determination of the incremental cost-effectiveness by prospectively collecting economic and resource utilization information. The objective is to determine an incremental cost effectiveness ratio reported as a cost per subsequent surgery avoided for both treatment arms. The mean overall cost per patient for each of the two study treatment arms will be calculated to determine the addition cost per surgery avoided.
Measured: Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2019
- Study startOct 2020 (estimated)
- Primary completionOct 2025 (estimated)
- Study completionOct 2026 (estimated)
Why it stopped: Feasibility couldn't be worked out
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bone MetastasesStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to receive 1 of the 2 treatment arms.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Patrick Henry, MD FRCS(C), Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04109937
- Sponsor's protocol ID
- EXPLORE
- Acronym
- EXPLORE
- Status last verified
- May 2023
- First submitted
- 27 Sep 2019
- Last updated
- 6 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Multicenter Randomized Trial Assessing the Efficacy of Post-Operative Conventional External Beam Radiation Therapy Following Orthopaedic Surgery in Patients With Lower Extremity Bone Metastases
- ClinicalTrials.gov ID
- NCT04109937
- Acronym / sponsor ID
- EXPLORE / EXPLORE
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Feasibility couldn't be worked out
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- Oct 2020 (estimated)
- Primary completion
- Oct 2025 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 1 Oct 2019 (actual)
- 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.
The objective of the present study is to evaluate the effectiveness of post-operative radiation therapy in lower extremity bone metastases. This trial will compare the health outcomes of patients receiving radiation therapy after Orthopaedic surgery to patients who will not receive radiation therapy post-surgery. The primary objective of the study is to compare the need for a subsequent surgery at the same treatment site within 12 months of the initial surgery. Additionally, the need for radiation or re-irradiation, functional status, performance status, pain scores, radiologically detected local disease progression, and overall length of survival will be compared at clinical endpoints for the two study arms. It is hypothesized that those randomized to receive post-operative radiation therapy will less likely need a subsequent surgery within the 12 months after the primary surgical intervention. This may optimize the quality of life for this patient population.
Detailed description
The incidence of bone metastases in advanced cancer patients is substantial, representing 70% of all metastatic sites. Approximately 5-10% of all patients with bone metastases develop pathological fractures. Surgical reconstruction can be helpful following fracture or prophylactically in cases of an impending fracture. In these cases, post-operative radiation is the current clinical practice in North America and many countries around the world. Post-operative radiation has the potential to support bone healing and prevent tumor progression while also decreasing the need for subsequent orthopaedic surgeries to the same site. A recent systematic review, however, challenged the evidence on its efficacy and adoption as standard of care in this patient population. As well, post-operative radiation requires additional visits to the radiation centre (associated with added costs and efforts for both the patients and the healthcare system). There is also a "pain flare" phenomenon, in which up to 40% of patients receiving radiation for palliative bone metastases experience pain within 1-5 days following radiation. The pain can last for 10 days and may acutely mask potential clinical benefits of radiation.
Given that there is potential negative impact to these patients who are palliative with a relatively short lifespan, it is important that the efficacy of post-operative radiation is rigorously evaluated.
We propose a multicenter randomized controlled trial to assess the efficacy of post-operative radiation following orthopaedic surgery in patients with lower extremity bone metastases. 300 patients with pending or established lower extremity pathological fracture will be recruited to a trial of surgery alone vs. surgery with post-operative radiation. The primary endpoint is a second surgery to the same site within 12 months. Secondary outcomes include quality of life, pain and functional outcome markers, radiation or re-irradiation as applicable, a second surgery within 24 months for those patients alive, overall survival and cost effectiveness.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will be randomized to receive 1 of the 2 treatment arms.
| Arm | Type | Receives |
|---|---|---|
| Surgery Alone | No intervention | –Patients with lower extremity bone metastases will receive surgical fixation/reconstruction but will not receive any post-operative radiation therapy. |
| Surgery and Post-Operative Radiation Therapy | Active comparator | Radiation: External beam radiation therapyPatients with lower extremity bone metastases will receive surgical fixation/reconstruction and will receive any post-operative radiation therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Is the patient 18 years of age or older at the time of randomization?
- Does the patient have histologically or cytologically proven malignancy?
- Does the patient have imaging confirming presence of bone metastases corresponding to clinically painful area?
- Does the patient have established bone metastatic pathological fracture(s) lower extremity OR has impending pathological fracture(s)?
- Does patient have KPS ≥40 with estimated survival of ≥ 6 months?
Key exclusion criteria (5 listed)
- Did the patient have a prior impending or prior pathological fracture to the site and was previously fixed with orthopaedic surgery?
- Did the patient receive prior radiation to the site (external beam or stereotactic body radiation)?
- Did the patient have a radio-resistant tumor (renal cell carcinoma or melanoma)?
- Did the patient plan for radical resection of the bone metastases?
- Did the patient receive or is planning to receive other intra-operative tumor ablative therapies?
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 |
|---|---|---|
| External beam radiation therapyThe post-operative radiation will cover entire prosthesis/surgical fixation device and will consist of the dose fractionation of: 20 Gy in 5 fractions or 30 Gy in 10 fractions. | Radiation | Surgery and Post-Operative Radiation Therapy |
Primary outcome
Subsequent surgery after primary surgery
Time frame: 12 months following the date of primary surgery
Requirement of a subsequent surgery
8 secondary outcomes
Re-irradiation/radiation
Time frame: Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Subsequent surgery (between 13 months and 24 months)
Time frame: Between 13 months and 24 months following date of primary surgery
Post-operative functional status and Karnofsky Performance Status (KPS)
Time frame: Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Post-operative pain and analgesic use
Time frame: Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Radiologically determined local progression
Time frame: Months 3, 6, 12, 18, and 24
Quality of life through functional ability
Time frame: Day of randomization, weeks 2 and 6, months 3, 6, 12, 18, and 24
Overall survival
Time frame: Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Cost-effectiveness
Time frame: Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2023.
- Individual participant dataSharing planned: Undecided
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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.
Patrick Henry, MD FRCS(C) principal investigator
Sunnybrook Health Sciences Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing External beam radiation therapy in people with Bone Metastases and Lower Extremity Fracture, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
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 6 inclusion and 5 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: withdrawn, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Subsequent surgery after primary surgery (time frame: 12 months following the date of primary surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 May 2023.