4-weekly Versus 12-weekly Administration of Bone-targeted Agents in Patients With Bone Metastases (REaCT-BTA)

A Pragmatic Randomised, Multicentre Trial Comparing 4-weekly Versus 12-weekly Administration of Bone-targeted Agents in Patients With Bone Metastases From Either Castration-resistant Prostate Cancer or Breast Cancer - The REaCT-BTA Study

The current Rethinking Clinical Trials (REaCT) trial will compare two schedules(12- vs. 4-weekly) of bone-targeting agents (BTAs) to evaluate quality of life, pain and skeletal events within the Canadian Health Care System. This study will use an "integrated consent model" that involves "oral consent" rather than a written informed consent writing process as the study is comparing standard schedules and not a new administration schedule.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Prostate Cancer; Metastasis
• Intervention / Treatment: Drug: Pamidronate; Drug: Denosumab; Drug: Zoledronate

Detailed Description

Bone metastases are common in patients with advanced breast and prostate cancers. Skeletal metastases can be associated with reduced Quality of Life (QoL), pain and skeletal-related events (SREs) (defined as pathological fractures, surgery/radiotherapy to bone, spinal cord compression and hypercalcaemia). Maintaining QoL while avoiding or delaying SREs are the main goals of therapy. Patients therefore receive bone-targeted agents (e.g. pamidronate, zoledronate and denosumab) which are typically given every 4 weeks. However, this 4 week dosing is based on convenience so the treatment could be given concurrently with chemotherapy. The half-life of these drugs in the bone is many months or even years. Hence studies have been performed evaluating 12-weekly therapy. These have confirmed similar palliative outcomes in the 4 vs 12-weekly groups for both breast and prostate cancer patients. However, there remains clinical equipoise about which dosing interval physicians prescribe. The current trial will compare these two schedules of bone-targeting agents (12- vs. 4-weekly) to evaluate quality of life, pain and skeletal events within the Canadian Health Care System. This study will use an "integrated consent model" that involves "oral consent" rather than a written informed consent writing process as the study is comparing standard schedules and not a new administration schedule.

• Study Type: Interventional
• Enrollment (Actual): 263
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada
      • The Ottawa Hospital Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with either radiologically and/or histologically confirmed bone metastases from castrate resistant prostate cancer (36) or breast cancer.
• About to start or currently receiving BTA therapy.
• Serum creatinine >30 ml/min and corrected serum calcium ≥ 2 mmol/l
• Age ≥ 18 years.
• Able to provide verbal consent

Exclusion Criteria:

• For CRPC patients - Definite contraindication for denosumab at baseline (e.g. hypocalcaemia [Albumin-corrected serum calcium < 2.0 mmol/l]).
• History of or current evidence of osteonecrosis of the jaw.
• Radiotherapy or surgery to the bone planned within 4 weeks after randomization.
• Known hypersensitivity to trial drug or hypersensitivity to any other component of the trial drug (e.g. fructose).
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 4 weekly bone-targeted agent x 1 year; Bone targeting agents as standard of care	Drug: Pamidronate; Bone-targeted agent as standard of care; Other Names: Aredia; Drug: Denosumab; Bone-targeted agent as standard of care; Other Names: Prolia; Drug: Zoledronate; Bone-targeted agent as standard of care; Other Names: Zometa
Active Comparator: 12 weekly bone-targeted agent x 1 year; Bone targeting agents as standard of care	Drug: Pamidronate; Bone-targeted agent as standard of care; Other Names: Aredia; Drug: Denosumab; Bone-targeted agent as standard of care; Other Names: Prolia; Drug: Zoledronate; Bone-targeted agent as standard of care; Other Names: Zometa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health related quality of life scores measured with European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Functional Domain (Physical Subdomain)	Units on a scale	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain will be measured through the EORTC-Quality of Life Questionnaire (QLQ)-BM22 (pain domain)	Units on a scale	1 year
Health related quality of life scores	Units on a scale	1 year
Time to development of symptomatic skeletal events (SSEs)	SSEs defined from the date of randomization until the first date a patient experiences an SSE (an on-study SSE is defined as: use of radiotherapy to relieve skeletal symptoms, new symptomatic pathological bone fractures (vertebral or non-vertebral), spinal cord compression, tumour related orthopedic surgical intervention, hypercalcaemia). Any patient who does not experience a SSE will be censored on the last date the patient can be confirmed as SSE-free. Multiple measurements will be aggregated to arrive at one reported value.	2 year
Total number of and time to subsequent on study SSE - to calculate Skeletal Morbidity Rates	Multiple measurements will be aggregated to arrive at one reported value.	2 year
For sites where Edmonton Symptom Assessment Scores (ESAS) are performed as standard of care, the ESAS scores will also be collected.	Units on a scale	2 year
Adverse events/ toxicity profiles will be compared between the two different approaches.		2 year
An economic analysis on Health Services Issues	We will perform a cost utility analysis alongside this pragmatic randomized controlled trial. The cost effectiveness of 4-week compared to 12-week BTA will be assessed in terms of the incremental cost per quality adjusted life year (QALY) gained from the perspective of health care system. Resource use and health utility will be measured from the trial at the follow up interviews. Health utility values would be estimated from the study questionnaires.	1 year

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Mark Clemons, MD, The Ottawa Hospital

Publications and helpful links

General Publications

• Tu MM, Clemons M, Stober C, Jeong A, Vandermeer L, Mates M, Blanchette P, Joy AA, Aseyev O, Pond G, Fergusson D, Ng TL, Thavorn K. Cost-Effectiveness Analysis of 12-Versus 4-Weekly Administration of Bone-Targeted Agents in Patients with Bone Metastases from Breast and Castration-Resistant Prostate Cancer. Curr Oncol. 2021 May 13;28(3):1847-1856. doi: 10.3390/curroncol28030171.

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: March 10, 2016
• First Submitted That Met QC Criteria: March 22, 2016
• First Posted (Estimate): March 29, 2016

Study Record Updates

• Last Update Posted (Actual): December 2, 2020
• Last Update Submitted That Met QC Criteria: December 1, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Breast Diseases; Prostatic Diseases; Neoplastic Processes; Breast Neoplasms; Prostatic Neoplasms; Neoplasm Metastasis; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid; Denosumab; Pamidronate
• Other Study ID Numbers: 16-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no plan to make individual participant data available.