Effects of Aromatase Inhibitor Therapy on Muscle Function

Breast Cancer Clinical Trial

Official title:

A Pilot Study Examining Molecular and Clinical Effects of Aromatase Inhibitor Therapy on Skeletal Muscle Function in Early Stage Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03581552
• Other study ID #: IUSCC-0647
• Status: Completed
• Start date: July 26, 2018
• Est. completion date: February 7, 2020

Study information

• Verified date: May 2021
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a pilot study designed to examine changes in muscle function after Aromatase Inhibitor (AI) therapy, at both the molecular and clinical level.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: February 7, 2020
• Est. primary completion date: February 7, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years

2. Post-menopausal

3. Diagnosis of ductal carcinoma in situ (DCIS) or stage I, II, or III ER positive breast cancer

4. Plan to initiate an AI per treating physician.

5. Completion of all primary therapy for breast cancer, including surgery, radiation, and chemotherapy (should be completed 14 days or more prior to obtaining the baseline muscle biopsy). Ongoing HER2 targeted therapy with trastuzumab and/or pertuzumab is allowed. Ongoing neratinib therapy is not allowed.

6. Body weight less than 350 lbs., as dictated by the weight limit for DXA (dual energy x-ray absorptiometry) scanner

7. Must be willing to undergo muscle biopsy at baseline and after 24 weeks of AI therapy

8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at the time of study enrollment

9. Informed consent and authorization of the release of health information must be obtained according to institutional guidelines

Exclusion Criteria:

1. Unwilling to co-enroll into the FIT core study

2. Diagnosis of severe osteopenia or osteoporosis, defined as a bone mineral density of = 2.0 standard deviations below the young adult female reference mean (T score)

3. Diagnosis of other disorder affecting bone function or turnover, such as Paget's disease, renal osteodystrophy, parathyroid disorders, or vitamin D deficiency/osteomalacia

4. Prior history of non-traumatic, fragility bone fracture

5. Any muscle or neuromuscular disorder affecting muscle function, such as muscular dystrophy, myositis, or amyotrophic lateral sclerosis

6. Any condition precluding power protocol participation (i.e. exertion on a stationary bicycle), including: New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled angina, myocardial infarction in the prior 12 months, orthopedic surgery in the previous 6 months or plans for orthopedic surgery during the study period, chronic uncontrolled pulmonary conditions such as uncontrolled asthma (symptoms > 2 days/week) or dyspnea requiring oxygen, symptomatic peripheral vascular disease, or any other comorbidity that would interfere with the ability to complete and comply with the protocol in the opinion of the investigator

7. Need for daily anticoagulation use

8. Allergy to local anesthetic

9. Locally recurrent or metastatic breast cancer a. History of prior treated malignancies, other than breast cancer, that are now stable, are in remission, and do not require active therapy, are acceptable.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Cancer Female
• Breast Neoplasms

Locations

Country	Name	City	State
United States	IU Simon Cancer Center	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Tarah J Ballinger, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in calstabin1 binding to RyR1 channels in skeletal muscle	Changes in calstabin1 binding to RyR1 channels in skeletal muscle of breast cancer patients pre and post exposure to adjuvant aromatase inhibitor therapy	through day 168 of aromatase inhibitor therapy
Secondary	Changes in ryanodine receptor/calcium release channel (RyR1) oxidation in skeletal muscle	To estimate changes in RyR1 oxidation in skeletal muscle of breast cancer patients, pre- and post- exposure to adjuvant aromatase inhibitor therapy	through day 168 of aromatase inhibitor therapy
Secondary	Relationship between changes in RyR1 biochemistry and measures of muscle function	To explore the relationship between changes in RyR1 biochemistry and measures of muscle function, including muscle power as measured by isokinetic dynamometry	through day 168 of aromatase inhibitor therapy
Secondary	Relationship between markers of bone turnover and changes in RyR1 biochemistry	To explore the relationship between markers of bone turnover and changes in RyR1 biochemistry (calstabin binding to RyR1)	through day 168 of aromatase inhibitor therapy
Secondary	Relationship between markers of bone turnover and changes in muscle function	To explore the relationship between markers of bone turnover and changes in muscle function in terms of muscle power assessed by isokinetic dynamometry	through day 168 of aromatase inhibitor therapy
Secondary	Characterize the timing of development of muscle dysfunction following initiation of aromatase inhibitor therapy	To better characterize the timing of development of muscle dysfunction following initiation of aromatase inhibitor therapy, in terms muscle power measured by isokinetic dynamometry	through day 168 of aromatase inhibitor therapy
Secondary	Feasibility of repeated muscle biopsies in patients with early stage breast cancer initiating aromatase inhibitor therapy	5. To describe the feasibility of repeated muscle biopsies in patients with early stage breast cancer initiating aromatase inhibitor therapy, in terms of rate of completion of baseline and follow up biopsy	through day 168 of aromatase inhibitor therapy