Breast Cancer Women on Aromatase Inhibitors Treatment (B-ABLE)

• ClinicalTrials.gov Identifier: NCT03811509
• Recruitment Status: Recruiting
• First Posted: January 22, 2019
• Last Update Posted: January 28, 2019
• Sponsor: Parc de Salut Mar
• Collaborator: Instituto de Salud Carlos III
• Information provided by (Responsible Party): Parc de Salut Mar

Study Description

Brief Summary:

The main objective of the study is to improve the life quality of women treated with AI. Cohort B-ABLE is designed to evaluate musculoskeletal events derived of using AI in breast cancer women. The project objectives are the analysis of the AI deleterious effect on bone microarchitecture and early determination of the risk of fragility fracture with dual energy x-ray absorptiometry (DEXA), lumbar spine Rx, Trabecular Bone Score (TBS) and microindentation. Determination of physiological causes of the AI-related arthralgia by analyzing joint degradation markers, steroid hormone levels remaining in blood and functional magnetic resonance, before and after three months of AI treatment

Condition or disease	Intervention/treatment	Phase
Osteoporosis; Osteoporosis Fracture; Arthralgia Generalized	Drug: bisphosphonate	Phase 4

Detailed Description:

Postmenopausal women with breast cancer treated with aromatase inhibitors (AI) have a higher incidence of osteoporosis, fractures and other musculoskeletal symptoms, particularly pain and stiffness. B-ABLE is a clinical, prospective cohort study carried out in both Breast Cancer and Bone Metabolism Units of the Hospital del Mar in Barcelona. Currently, 780 postmenopausal Caucasian women with early breast cancer and candidates for adjuvant AI treatment were included and predicted to reach more than 1000 patients. The main objective of the study is to improve the life quality of women treated with AI. Cohort B-ABLE is designed to evaluate musculoskeletal events derived of using AI in breast cancer women. The project objectives are the analysis of the AI deleterious effect on bone microarchitecture and early determination of the risk of fragility fracture with DEXA, lumbar spine Rx, TBS and microindentation. Determination of physiological causes of the AI-related arthralgia by analyzing joint degradation markers, steroid hormone levels remaining in blood and functional magnetic resonance, before and after three months of AI treatment. The study results will help to decide the most appropriate treatment for each patient in order to minimize AI-related side effects and hence avoid discontinuation of adjuvant therapy treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1000 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: All patents receive aromatase inhibitors Patients without osteoporosis receive only calcium and vitamin D Patients with osteoporosis receive antiresorptive treatment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Study for Improving Life Quality in Breast Cancer Women Treated With Aromatase Inhibitors: Cohort B-ABLE
• Actual Study Start Date: January 1, 2016
• Estimated Primary Completion Date: January 1, 2021
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: AI with osteoporosis; Patients with osteoporosis receive intervention with antiresorptive treatment, bisphosphonates or denosumab . All patients receive calcium and Vit D supplements All patients receive by protocol aromatase inhibitors for breast cancer treatment, letrozole, exemestane for 5 o 10 years.	Drug: bisphosphonate; antiresorptives; Other Name: denosumab
No Intervention: AI without osteoporosis; All patients receive calcium and Vit D supplements All patients receive by protocol aromatase inhibitors for breast cancer treatment, letrozole, exemestane for 5 o 10 years.

Outcome Measures

Primary Outcome Measures :

1. bone mass measured by dual energy x-ray absorptiometry (DEXA) densitometry [ Time Frame: change from baseline, 12 months, 24 months, 36 months, 48 months 60 months and 1 year after completion of aromatase treatment ]
   bone mas normal, osteopenia or osteoporosis related with WHO definition of osteoporosis and Trabecular Bone Score: normal, mild degratation and high degradation
2. Fragility fractures assessed by xRay [ Time Frame: incidence of new fractures at 12 months, 24 months, 36 months, 48 months 60 months of aromatase treatment ]
   vertebral and non vertebral fractures, hip fractures
3. Bone Mineral Strength (BMSi) [ Time Frame: change from baseline, 12 months, and 60 months of aromatase treatment ]
   bone microindentation
4. Arthralgia [ Time Frame: change from baseline, 12 months, 24 months, 36 months, 48 months 60 months and 1 year after completion of aromatase treatment ]
   joint pain measured by analogic visual scale range 0= no pain 10= worse pain

Secondary Outcome Measures :

1. bone turnover markers [ Time Frame: change from baseline, 12 months, 24 months, 36 months, 48 months 60 months and 1 year after completion of aromatase treatment ]
   C-telopeptide (Ctx), Procollagen type 1 amino-terminal propeptide (P1NP) Bone Alkaline Phosphatase (AP)
2. cartilage degradation markers [ Time Frame: change from baseline and 12 months of aromatase treatment ]
   C-telopeptide II, Procollagen type 2 amino-terminal propeptide (P2NP)

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Postmenopausal women with early breast cancer estrogen receptor with aromatase inhibitors treatment

Exclusion Criteria:

• Previous treatment with antiresorptive treatment for osteoporosis secondary osteoporosis, as corticosteroids, Hyperparathyroidism, Kidney Chronic disease, previous treatment with aromatase inhibitors Diabetes mellitus type 1 Fibromyalgia

Contacts and Locations

Contacts

Contact: Xavier Nogues, MD; 34932483246; xnogues@parcdesalutmar.cat

Contact: Natalia Garcia-Giralt, PhD; 34933160445; ngarcia@imim.es

Locations

Spain

Xavier Nogues; Recruiting

Barcelona, Spain, 08015

Contact: Xavier Nogues, MD 932483246 xnogues@parcdesalutmar.cat

Contact: Natalia Garcia-Giralt, Phd 34933160445

Sub-Investigator: Sonia Servitja, MD

Sub-Investigator: Ignasi Tusquets, MD

Sub-Investigator: Marta Pineda, PhD

Sub-Investigator: Isabel Aymar

Sub-Investigator: Jaime Rodriguez-Morera, MD

Sub-Investigator: Adolfo Díez-Pérez, MD

Sub-Investigator: Maria Martinez, MD

Sub-Investigator: Tamara Martos, MD

Sponsors and Collaborators

Parc de Salut Mar

Instituto de Salud Carlos III

More Information

Publications of Results:

Servitja S, Martos T, Rodriguez Sanz M, Garcia-Giralt N, Prieto-Alhambra D, Garrigos L, Nogues X, Tusquets I. Skeletal adverse effects with aromatase inhibitors in early breast cancer: evidence to date and clinical guidance. Ther Adv Med Oncol. 2015 Sep;7(5):291-6. doi: 10.1177/1758834015598536. Review.

Other Publications:

Servitja S, Nogués X, Prieto-Alhambra D, Martínez-García M, Garrigós L, Peña MJ, de Ramon M, Díez-Pérez A, Albanell J, Tusquets I. Bone health in a prospective cohort of postmenopausal women receiving aromatase inhibitors for early breast cancer. Breast. 2012 Feb;21(1):95-101. doi: 10.1016/j.breast.2011.09.001. Epub 2011 Sep 15.

Nogues X, Servitja S, Peña MJ, Prieto-Alhambra D, Nadal R, Mellibovsky L, Albanell J, Diez-Perez A, Tusquets I. Vitamin D deficiency and bone mineral density in postmenopausal women receiving aromatase inhibitors for early breast cancer. Maturitas. 2010 Jul;66(3):291-7. doi: 10.1016/j.maturitas.2010.03.012. Epub 2010 Apr 15.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Pineda-Moncusí M, Servitja S, Tusquets I, Diez-Perez A, Rial A, Cos ML, Campodarve I, Rodriguez-Morera J, Garcia-Giralt N, Nogués X. Assessment of early therapy discontinuation and health-related quality of life in breast cancer patients treated with aromatase inhibitors: B-ABLE cohort study. Breast Cancer Res Treat. 2019 Aug;177(1):53-60. doi: 10.1007/s10549-019-05289-7. Epub 2019 May 24.

• Responsible Party: Parc de Salut Mar
• ClinicalTrials.gov Identifier: NCT03811509
• Other Study ID Numbers: 4604010730
• First Posted: January 22, 2019
• Last Update Posted: January 28, 2019
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Publication in Oncology , Endocrinology and bone metabolism journals
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: Data will become available in the next year and every time we have outcomes available
• Access Criteria: By asking CEIC Parc de Salut Mar

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Parc de Salut Mar:

osteoporosis; aromatase inhibitors; breast cancer; microindentation; arthralgia; musculoskeletal pain

Additional relevant MeSH terms:

Osteoporosis; Arthralgia; Osteoporotic Fractures; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Joint Diseases; Pain; Neurologic Manifestations; Fractures, Bone; Wounds and Injuries; Denosumab; Diphosphonates; Bone Density Conservation Agents; Physiological Effects of Drugs