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

NCT04549207 | Active Not Recruiting Phase 4

• 1 other identifier: REaCT-Hold BMA
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Breast Cancer; Castration-resistant Prostate Cancer

Keywords

Bone modifying agents; BMA; Breast cancer; Castration-resistant prostate cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Symptomatic Skeletal Event (SSE)

  2 years post-randomization

• Time to development of Symptomatic Skeletal Event

  2 years post-randomization

• Symptomatic Skeletal Event-free survival

  2 years post-randomization

• Skeletal morbidity

  2 years post-randomization

• Quality of life of cancer patients using the EORTC-QLQ-C30

  48 weeks post-randomization

Other Outcomes (3)

• Frequency of subsequent de-escalation or discontinuation of BMAs

  2 years post-randomization

• Frequency of restarting standard dosing BMA

  2 years post-randomization

• Overall survival

  2 years post-randomization

Study Arms (2)

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.

Drug: Bone modifying agent

De-escalate BMA to once every 24 weeks

ACTIVE COMPARATOR

Bone modifying agent once every 24 weeks.

Drug: Bone modifying agent

Interventions

Bone modifying agent DRUG

Use of bone modifying agent

Also known as: Zoledronate, Denosumab, Pamidronate

De-escalate BMA to once every 24 weeks; Standard BMA frequency

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (5)

William Osler Health System

Brampton, Ontario, L6R 3J7, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Southlake Regional Health Centre

Newmarket, Ontario, L3Y 2P9, Canada

Location

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Location

Thunder Bay Regional Health Sciences Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Related Publications (3)

• 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.

  PMID: 32535678 BACKGROUND

• 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.

  PMID: 33294318 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.

  PMID: 34023950 BACKGROUND

Related Links

• The Rethinking Clinical Trials (REaCT) website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Zoledronic Acid; Denosumab; Pamidronate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Terry Ng, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2020
• First Posted: September 16, 2020
• Study Start: October 9, 2020
• Primary Completion: April 17, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 28, 2025

Record last verified: 2025-11

Locations

CA (5)