Study of Oral Bisphosphonate for Osteopenic Women Treated With Adjuvant Aromatase Inhibitors (BONADIUV)

A Single--blind, Randomized, Placebo--controlled Phase II Study to Evaluate the Impact of Oral Bisphosphonate Treatment on Bone Mineral Density in Osteopenic Women Receiving Adjuvant Aromatase Inhibitors - BONADIUV Trial

A single--blind, randomized, placebo--controlled phase II study to evaluate the impact of oral bisphosphonate treatment on bone mineral density in osteopenic women receiving aromatase inhibitors as adjuvant treatment.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Ibandronic acid; Drug: Placebo

Detailed Description

Aromatase inhibitors (AIs) are the adjuvant treatment of choice in postmenopausal women with early, hormone receptor-positive breast cancer (BC), because they produce improved survival rates compared with tamoxifen. Progressive bone loss and subsequent fractures are associated with adjuvant AIs, administered either alone or sequentially after tamoxifen in postmenopausal women with early BC. Recent findings of National Surgical Adjuvant Breast and Bowel Project (NSABP) B-34 also suggest that bisphosphonates might have anticancer benefits for older postmenopausal women. "BONADIUV" trial is a single-blind, randomized, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on bone mineral density (BMD) in women taking AIs.

Patients undergo a baseline BMD and if they result osteopenic (lumbar spine and/or trochanter -1< T-score <2.5), they are randomized in a 1:1 ratio to receive either placebo or oral ibandronate. All patients receive oral supplementation of calcium and Vitamin D3, once daily for two years. Study duration is 2 year, with planned six-months evaluation.

A total of 72 patients per arm of treatment are needed to obtain a 85% statistical power in order to detect a 2% BMD mean difference between the two arms. Considering a 15% dropout, around 82 patients per arm are planned to be enrolled.

• Study Type: Interventional
• Enrollment (Actual): 171
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Florence, Italy, 50134
    • Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Diagnosis of hormone-receptor positive early breast cancer
• Menopausal status
• Age < 75 years
• Written informed consent

Exclusion Criteria:

• Premenopausal status at time of randomization
• Comorbidities with increased risk of osteoporosis (primary hyperparathyroidism, hyperthyroidism, rheumatoid arthritis)
• BMI < 18
• Chronic use of steroids
• Use of bisphosphonates at time of randomization
• Psychiatric disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Ibandronic acid; Ibandronic acid 150 mg per os per month for two years	Drug: Ibandronic acid; 150 mg per month oral ibandronate; Other Names: Ibandronate
Placebo Comparator: Arm B: Placebo; Placebo per os per month for two years	Drug: Placebo; 1 oral capsule of placebo per month; Other Names: Placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lumbar spine and trochanter T-score mean difference as measure of BMD variation	Lumbar spine and trochanter T-score mean difference	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Number of Participants with Adverse Events	2 years
Overall Survival (OS)	Overall Survival (OS) rate	5 years
Disease-free Survival (DFS)	Disease-free Survival (DFS) rate	5 years

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria Careggi
• Investigators: Principal Investigator: Lorenzo Livi, Professor, AOU Careggi - University of Florence, Florence, Italy; Principal Investigator: Meattini Icro, M.D., AOU Careggi - University of Florence, Florence, Italy

Publications and helpful links

General Publications

• Livi L, Scotti V, Desideri I, Saieva C, Cecchini S, Francolini G, Becherini C, Delli Paoli C, Visani L, Salvestrini V, De Feo ML, Nori J, Bernini M, Sanchez L, Orzalesi L, Bianchi S, Meattini I. Phase 2 placebo-controlled, single-blind trial to evaluate the impact of oral ibandronate on bone mineral density in osteopenic breast cancer patients receiving adjuvant aromatase inhibitors: 5-year results of the single-centre BONADIUV trial. Eur J Cancer. 2019 Feb;108:100-110. doi: 10.1016/j.ejca.2018.12.005. Epub 2019 Jan 14.

Helpful Links

• Eur J Cancer. 2019 Feb;108:100-110. doi: 10.1016/j.ejca.2018.12.005. Epub 2019 Jan 14.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: November 24, 2015
• First Submitted That Met QC Criteria: November 25, 2015
• First Posted (Estimate): November 30, 2015

Study Record Updates

• Last Update Posted (Actual): October 22, 2019
• Last Update Submitted That Met QC Criteria: October 18, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: aromatase inhibitors; breast cancer; bone mineral density
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Bone Density Conservation Agents; Ibandronic Acid
• Other Study ID Numbers: BONADIUV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO