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

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)

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

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Bone modifying agent

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lisa Vandermeer; Phone Number: 73039 613-737-7700; Email: lvandermeer@toh.ca
• Study Contact Backup: Name: Marta Sienkiewicz; Phone Number: 77212 613-737-7700; Email: msienkiewicz@ohri.ca

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada
      • Recruiting
      • The Ottawa Hospital Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard BMA frequency; 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; Use of bone modifying agent; Other Names: Denosumab; Zoledronate; Pamidronate
Active Comparator: De-escalate BMA to once every 24 weeks; Bone modifying agent once every 24 weeks.	Drug: Bone modifying agent; Use of bone modifying agent; Other Names: Denosumab; Zoledronate; 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

Other Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Terry Ng, MD, Ottawa Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2020
• Primary Completion (Anticipated): November 1, 2024
• Study Completion (Anticipated): November 1, 2025

Study Registration Dates

• First Submitted: September 1, 2020
• First Submitted That Met QC Criteria: September 8, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Breast cancer; Castration-resistant prostate cancer; Bone modifying agents; BMA
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid; Denosumab; Pamidronate
• Other Study ID Numbers: REaCT-Hold BMA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No