External Beam Radiation Therapy Post Surgery in Patients With Lower Extremity Bone Metastases Randomized Efficacy Trial (EXPLORE)
Primary Purpose
Bone Metastases, Lower Extremity Fracture, Pathological Fracture
Status
Withdrawn
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
External beam radiation therapy
Sponsored by
About this trial
This is an interventional treatment trial for Bone Metastases
Eligibility Criteria
Inclusion Criteria:
- 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?
Exclusion Criteria:
- 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?
Sites / Locations
- Sunnybrook Health Sciences Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Active Comparator
Arm Label
Surgery Alone
Surgery and Post-Operative Radiation Therapy
Arm Description
Patients with lower extremity bone metastases will receive surgical fixation/reconstruction but will not receive any post-operative radiation therapy.
Patients with lower extremity bone metastases will receive surgical fixation/reconstruction and will receive any post-operative radiation therapy.
Outcomes
Primary Outcome Measures
Subsequent surgery after primary surgery
Requirement of a subsequent surgery
Secondary Outcome Measures
Re-irradiation/radiation
Requirement for re-irradiation in arm 2 or radiation in arm 1
Subsequent surgery (between 13 months and 24 months)
Requirement of subsequent surgery past 12 months (between 13 months and 24 months)
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
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.
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.
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
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
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.
Full Information
NCT ID
NCT04109937
First Posted
September 27, 2019
Last Updated
May 2, 2023
Sponsor
Sunnybrook Health Sciences Centre
1. Study Identification
Unique Protocol Identification Number
NCT04109937
Brief Title
External Beam Radiation Therapy Post Surgery in Patients With Lower Extremity Bone Metastases Randomized Efficacy Trial
Acronym
EXPLORE
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Feasibility couldn't be worked out
Study Start Date
October 2020 (Anticipated)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
October 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sunnybrook Health Sciences Centre
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bone Metastases, Lower Extremity Fracture, Pathological Fracture, Impending Fracture
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomized to receive 1 of the 2 treatment arms.
Masking
None (Open Label)
Masking Description
Study is not blinded.
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Surgery Alone
Arm Type
No Intervention
Arm Description
Patients with lower extremity bone metastases will receive surgical fixation/reconstruction but will not receive any post-operative radiation therapy.
Arm Title
Surgery and Post-Operative Radiation Therapy
Arm Type
Active Comparator
Arm Description
Patients with lower extremity bone metastases will receive surgical fixation/reconstruction and will receive any post-operative radiation therapy.
Intervention Type
Radiation
Intervention Name(s)
External beam radiation therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Subsequent surgery after primary surgery
Description
Requirement of a subsequent surgery
Time Frame
12 months following the date of primary surgery
Secondary Outcome Measure Information:
Title
Re-irradiation/radiation
Description
Requirement for re-irradiation in arm 2 or radiation in arm 1
Time Frame
Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Title
Subsequent surgery (between 13 months and 24 months)
Description
Requirement of subsequent surgery past 12 months (between 13 months and 24 months)
Time Frame
Between 13 months and 24 months following date of primary surgery
Title
Post-operative functional status and Karnofsky Performance Status (KPS)
Description
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
Time Frame
Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Title
Post-operative pain and analgesic use
Description
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.
Time Frame
Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Title
Radiologically determined local progression
Description
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.
Time Frame
Months 3, 6, 12, 18, and 24
Title
Quality of life through functional ability
Description
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
Time Frame
Day of randomization, weeks 2 and 6, months 3, 6, 12, 18, and 24
Title
Overall survival
Description
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
Time Frame
Weeks 2 & 6, Months 3, 6, 12, 18, and 24
Title
Cost-effectiveness
Description
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.
Time Frame
Weeks 2 & 6, Months 3, 6, 12, 18, and 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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?
Exclusion Criteria:
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?
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Henry, MD FRCS(C)
Organizational Affiliation
Sunnybrook Health Sciences Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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External Beam Radiation Therapy Post Surgery in Patients With Lower Extremity Bone Metastases Randomized Efficacy Trial
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