Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The investigators propose to perform a pragmatic, multicenter, open-label, randomised clinical trial to demonstrate the efficacy and safety of either continuing or further de-escalating BMA after a minimum of two years of BMA treatment in patients with bone metastases from breast cancer and castration-resistant prostate cancer
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard BMA frequency | Active Comparator | Continue standard BMA frequency (every 4 or 12 weeks) as administered previously. If a change in BMA frequency (every 4 weeks to every 12 weeks OR every 12 weeks to every 4 weeks) was prescribed by the physician, this would still be considered on protocol treatment. |
|
| De-escalate BMA to once every 24 weeks | Active Comparator | Bone modifying agent once every 24 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bone modifying agent | Drug | Use of bone modifying agent |
|
| Measure | Description | Time Frame |
|---|---|---|
| Health related quality of life scores | Health related quality of life (HR-QoL) scores measured by the European Organisation for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire (QLQ)-C30 physical functioning subscale and the European Organisation for Research and Treatment of Cancer (EORTC)- Quality of Life Questionnaire (QLQ)- for patients with bone metastasis (BM)22 functional interference subscale. The EORTC-QLQ-C30 is an internationally accepted and validated tool in multiple large study cohorts capturing HR-QoL from a multi-dimensional and global perspective in oncology. EORTC-QLQ-BM22 has been validated for use specifically in bone metastases. They were developed in collaboration with patients, healthcare professionals and thorough review of the literature, and therefore important to all stakeholders; the scales are well-defined and easily measured, and HR-QoL is a relevant goal of care in the palliative care setting. | 48 weeks after randomization (one year of treatment) |
| Measure | Description | Time Frame |
|---|---|---|
| Symptomatic Skeletal Event (SSE) | Number of patients with one or more SSEs (defined as: use of radiotherapy to relieve skeletal symtoms, new symptomatic pathological bone fractures [vertebral or non-vertebral], spinal cord compression, tumour-related orthopedic surgical intervention, or hypercalcaemia] during trial period) up to 2 years post-randomization. | 2 years post-randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of subsequent de-escalation or discontinuation of BMAs | In the continuation arm, frequency of subsequent de-escalation or discontinuation of BMAs | 2 years post-randomization |
| Frequency of restarting standard dosing BMA |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Terry Ng, MD | Ottawa Hospital Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| William Osler Health System | Brampton | Ontario | L6R 3J7 | Canada | ||
| London Health Sciences Centre |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32535678 | Background | Ng TL, Tu MM, Ibrahim MFK, Basulaiman B, McGee SF, Srikanthan A, Fernandes R, Vandermeer L, Stober C, Sienkiewicz M, Jeong A, Saunders D, Awan AA, Hutton B, Clemons MJ. Long-term impact of bone-modifying agents for the treatment of bone metastases: a systematic review. Support Care Cancer. 2021 Feb;29(2):925-943. doi: 10.1007/s00520-020-05556-0. Epub 2020 Jun 13. | |
| 33294318 |
| Label | URL |
|---|---|
| The Rethinking Clinical Trials (REaCT) website | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Time to development of Symptomatic Skeletal Event | Defined from the date of randomization until the first date of patient experience an SSE. Any patient who does not experience an SSE will be censored on the last follow-up date and the patient can be confirmed as SSE-free (up to 2 years). | 2 years post-randomization |
| Symptomatic Skeletal Event-free survival | SSE-free survival (composite of time to first SSE and time to death) | 2 years post-randomization |
| Skeletal morbidity | Skeletal morbidity rate defined as ration of number of SSEs for each subject divided by the subject's time at risk in years. | 2 years post-randomization |
| Quality of life of cancer patients using the EORTC-QLQ-C30 | Assess quality of life of cancer patients using the EORTC-QLQ-C30 (cancer patient specific questionnaire) at each time point, up to and including 48 weeks ("one year of treatment") | 48 weeks post-randomization |
| Quality of life of cancer patients using the EORTC-QLQ-BM22 | Assess quality of life of cancer patients using the EORTC-QLQ-BM22 (patients with bone metastases specific questionnaire) at each time point, up to and including 48 weeks ("one year of treatment") | 48 weeks post-randomization |
| BMA-related toxicity rates | BMA-related toxicity rates (up to 2 years) based on standard of care blood tests and clinical assessments | 2 years post-randomization |
| Incremental cost-effectiveness rations | Defined as the difference in cost between two possible interventions, divided by the difference in their Quality Adjusted Life Year (QALY) gained. | 2 years post-randomization |
In the de-escalation arm, frequency of restarting standard dosing BMA (and the reasons for restarting)
| 2 years post-randomization |
| Overall survival | Overall survival during study duration | 2 years post-randomization |
| London |
| Ontario |
| N6A 5W9 |
| Canada |
| Southlake Regional Health Centre | Newmarket | Ontario | L3Y 2P9 | Canada |
| The Ottawa Hospital Cancer Centre | Ottawa | Ontario | Canada |
| Thunder Bay Regional Health Sciences Centre | Thunder Bay | Ontario | P7B 6V4 | Canada |
| AlZahrani M, Clemons M, Vandermeer L, Sienkiewicz M, Awan AA, Hutton B, Pond GR, Ng TL. Real-world practice patterns and attitudes towards de-escalation of bone-modifying agents in patients with bone metastases from breast and prostate cancer: A physician survey. J Bone Oncol. 2020 Nov 10;26:100339. doi: 10.1016/j.jbo.2020.100339. eCollection 2021 Feb. |
| 34023950 | Background | Alzahrani M, Clemons M, Sienkiewicz M, Shrem NS, McGee SF, Vandermeer L, Sehdev S, Savard MF, Awan A, Canil C, Hutton B, Pond G, Saunders D, Ng T. Perceptions around bone-modifying agent use in patients with bone metastases from breast and castration resistant prostate cancer: a patient survey. Support Care Cancer. 2021 Nov;29(11):6903-6912. doi: 10.1007/s00520-021-06238-1. Epub 2021 May 22. |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077211 | Zoledronic Acid |
| D000069448 | Denosumab |
| D000077268 | Pamidronate |
| ID | Term |
|---|---|
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided