Comparing Continuation or De-escalation of Bone Modifying Agents (BMA) in Patients Treated for Over 2 Years for Bone Metastases From Either Breast or Castration-resistant Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
The investigators propose is 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

Official Title
-----------------
A Randomised Trial Comparing Continuation or De-escalation of Bone Modifying Agents (BMA) in Patients Treated for Over 2 Years for Bone Metastases From Either Breast or Castration-resistant Prostate Cancer (REaCT-Hold BMA)

Conditions
-----------------
Breast Cancer, Castration-resistant Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Bone modifying agent


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with either radiologically and/or histologically confirmed bone metastases from castrate resistant prostate cancer or breast cancer who are currently receiving BMA Patient has received BMA for 2 or more years counting from the first BMA dose for bone metastases Age 18 years or older Able to provide verbal consent Exclusion Criteria: Definite contraindication for BMA History of, or current evidence of osteonecrosis of the jaw Radiotherapy or surgery to the bone planned within 4 weeks after randomization Current hypercalcemia defined as corrected serum calcium of > 3 mmol/L (from standard bloodwork completed within one month prior to treatment dose)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard BMA frequency<br>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. | Drug: Bone modifying agent<br>* Use of bone modifying agent<br>* Other names: Pamidronate;|
| Active Comparator: De-escalate BMA to once every 24 weeks<br>Bone modifying agent once every 24 weeks. | Drug: Bone modifying agent<br>* Use of bone modifying agent<br>* Other names: Pamidronate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | 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) | 

Secondary Outcome Measures

| Outcome Measure | 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bone modifying agents, BMA, Breast cancer, Castration-resistant prostate cancer