Clinical trial NCT02616744: Study of Oral Bisphosphonate for Osteopenic Women Treated With Adjuvant Aromatase Inhibitors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: aromatase inhibitors
breast cancer
bone mineral density
Lead sponsor: Azienda Ospedaliero-Universitaria Careggi
Sponsor class: OTHER
First posted: 2015-11-30
Enrollment: 171
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Lumbar spine and trochanter T-score mean difference as measure of BMD variation
timeFrame: 2 years
Secondary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 5 years
measure: Disease-free Survival (DFS)
timeFrame: 5 years
Other outcomes:
Locations:
city: Florence
country: Italy
facility: Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi
Study officials:
affiliation: AOU Careggi - University of Florence, Florence, Italy
name: Lorenzo Livi, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: AOU Careggi - University of Florence, Florence, Italy
name: Meattini Icro, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.