Clinical trial NCT02721433: 4-weekly Versus 12-weekly Administration of Bone-targeted Agents in Patients With Bone Metastases
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Breast Cancer
Prostate Cancer
Metastasis
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2016-03-29
Enrollment: 263
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Health related quality of life scores measured with European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Functional Domain (Physical Subdomain)
timeFrame: 1 year
Secondary outcomes:
measure: Pain will be measured through the EORTC-Quality of Life Questionnaire (QLQ)-BM22 (pain domain)
timeFrame: 1 year
measure: Health related quality of life scores
timeFrame: 1 year
measure: Time to development of symptomatic skeletal events (SSEs)
timeFrame: 2 year
measure: Total number of and time to subsequent on study SSE - to calculate Skeletal Morbidity Rates
timeFrame: 2 year
measure: For sites where Edmonton Symptom Assessment Scores (ESAS) are performed as standard of care, the ESAS scores will also be collected.
timeFrame: 2 year
measure: Adverse events/ toxicity profiles will be compared between the two different approaches.
timeFrame: 2 year
measure: An economic analysis on Health Services Issues
timeFrame: 1 year
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital Research Institute
state: Ontario
Study officials:
affiliation: The Ottawa Hospital
name: Mark Clemons, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.