- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04109937
External Beam Radiation Therapy Post Surgery in Patients With Lower Extremity Bone Metastases Randomized Efficacy Trial (EXPLORE)
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 Overview
Status
Intervention / Treatment
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 Type
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Patrick Henry, MD FRCS(C)
- Phone Number: 8741 416-967-8741
- Email: patrick.henry@sunnybrook.ca
Study Contact Backup
- Name: Ravi Tuazon, BSc
- Phone Number: 4285 416-480-4285
- Email: ravi.tuazon@sunnybrook.ca
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M4N 3M5
- Sunnybrook Health Sciences Centre
-
Contact:
- Patrick Henry, MD FRCS(C)
- Phone Number: 8741 416-967-8741
- Email: patrick.henry@sunnybrook.ca
-
Contact:
- Ravi Tuazon, BSc
- Phone Number: 4285 416-480-4285
- Email: ravi.tuazon@sunnybrook.ca
-
Principal Investigator:
- Patrick Henry, MD FRCS(C)
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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?
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
No Intervention: Surgery Alone
Patients with lower extremity bone metastases will receive surgical fixation/reconstruction but will not receive any post-operative radiation therapy.
|
|
Active Comparator: Surgery and Post-Operative Radiation Therapy
Patients with lower extremity bone metastases will receive surgical fixation/reconstruction and will receive any post-operative radiation therapy.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Subsequent surgery after primary surgery
Time Frame: 12 months following the date of primary surgery
|
Requirement of a subsequent surgery
|
12 months following the date of primary surgery
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Re-irradiation/radiation
Time Frame: Weeks 2 & 6, Months 3, 6, 12, 18, and 24
|
Requirement for re-irradiation in arm 2 or radiation in arm 1
|
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
|
Requirement of subsequent surgery past 12 months (between 13 months and 24 months)
|
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
|
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
|
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
|
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.
|
Weeks 2 & 6, Months 3, 6, 12, 18, and 24
|
Radiologically determined local progression
Time Frame: Months 3, 6, 12, 18, and 24
|
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.
|
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
|
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
|
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
|
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
|
Weeks 2 & 6, Months 3, 6, 12, 18, and 24
|
Cost-effectiveness
Time Frame: Weeks 2 & 6, Months 3, 6, 12, 18, and 24
|
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.
|
Weeks 2 & 6, Months 3, 6, 12, 18, and 24
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- EXPLORE
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Bone Metastases
-
University of CalgaryNot yet recruitingBone Metastases | Spine Metastases | Bone LesionCanada
-
Suzhou Suncadia Biopharmaceuticals Co., Ltd.Not yet recruitingPatients With Bone MetastasesChina
-
Luye Pharma Group Ltd.RecruitingBone Metastases From Solid TumorsChina
-
Shanghai JMT-Bio Inc.CompletedBone Metastases From Solid TumorsChina
-
Varian, a Siemens Healthineers CompanyRecruitingBone Metastases in the ThoraxUnited States
-
Ottawa Hospital Research InstituteWithdrawn
-
UMC UtrechtCompletedBone Metastases | Spinal MetastasesNetherlands
-
University of Roma La SapienzaCompletedBone Metastases | Secondary Bone CancerItaly
-
Shanghai JMT-Bio Inc.Not yet recruitingImaging Examination Shows at Least One Site With Bone Metastases From Soild Tumors
-
Heidelberg UniversityCompletedVertebral Bony MetastasesGermany
Clinical Trials on External beam radiation therapy
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingAnn Arbor Stage I Grade 1 Follicular Lymphoma | Ann Arbor Stage I Grade 2 Follicular Lymphoma | Ann Arbor Stage II Grade 1 Follicular Lymphoma | Ann Arbor Stage II Grade 2 Follicular Lymphoma | Ann Arbor Stage IV B-Cell Non-Hodgkin Lymphoma | Ann Arbor Stage I B-Cell Non-Hodgkin Lymphoma | Ann... and other conditionsUnited States
-
NRG OncologyNational Cancer Institute (NCI)RecruitingStage III Prostate Cancer AJCC v8 | Stage IVA Prostate Cancer AJCC v8United States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingHematopoietic and Lymphoid Cell Neoplasm | Metastatic Malignant Solid NeoplasmUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedProstate Adenocarcinoma | Stage III Prostate Cancer | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)RecruitingPain | Metastatic Malignant Neoplasm in the Bone | Malignant NeoplasmUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingInvasive Breast Carcinoma | Stage IA Breast Cancer AJCC v7 | Stage IB Breast Cancer AJCC v7 | Stage II Breast Cancer AJCC v6 and v7 | Stage IIA Breast Cancer AJCC v6 and v7 | Stage IIB Breast Cancer AJCC v6 and v7 | Ductal Breast Carcinoma In Situ | Stage I Breast Cancer AJCC v6United States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingInvasive Breast Carcinoma | Estrogen Receptor Negative | HER2/Neu Negative | Progesterone Receptor Negative | Triple-Negative Breast Carcinoma | HER2 Positive Breast Carcinoma | Stage I Breast Cancer AJCC v7 | Stage IA Breast Cancer AJCC v7 | Stage IB Breast Cancer AJCC v7 | Stage II Breast Cancer AJCC... and other conditionsUnited States
-
NRG OncologyNational Cancer Institute (NCI)Active, not recruitingPSA Progression | Stage III Prostate Adenocarcinoma | Stage IV Prostate AdenocarcinomaUnited States, Canada
-
City of Hope Medical CenterNational Cancer Institute (NCI)CompletedGastric Adenocarcinoma | Gastric Squamous Cell Carcinoma | Gastroesophageal Junction Adenocarcinoma | Metastatic Malignant Neoplasm in the Stomach | Stage IV Esophageal Adenocarcinoma AJCC v7 | Stage IV Esophageal Squamous Cell Carcinoma AJCC v7United States
-
Institut BergoniéInstitut National de la Santé Et de la Recherche Médicale, FranceCompleted