Clinical trial NCT03581552: Effects of Aromatase Inhibitor Therapy on Muscle Function
Official title: A Pilot Study Examining Molecular and Clinical Effects of Aromatase Inhibitor Therapy on Skeletal Muscle Function in Early Stage Breast Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Breast Cancer Female
Keywords: Post Menopausal
ER positive
Aromatase Inhibitor Therapy
Breast Cancer
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2018-07-10
Enrollment: 16
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Post menopausal women with non metastatic breast cancer planning to initiate aromatase inhibitor therapy at the IU Simon Cancer Center oncology clinic.

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Changes in calstabin1 binding to RyR1 channels in skeletal muscle
timeFrame: through day 168 of aromatase inhibitor therapy
Secondary outcomes:
measure: Changes in ryanodine receptor/calcium release channel (RyR1) oxidation in skeletal muscle
timeFrame: through day 168 of aromatase inhibitor therapy
measure: Relationship between changes in RyR1 biochemistry and measures of muscle function
timeFrame: through day 168 of aromatase inhibitor therapy
measure: Relationship between markers of bone turnover and changes in RyR1 biochemistry
timeFrame: through day 168 of aromatase inhibitor therapy
measure: Relationship between markers of bone turnover and changes in muscle function
timeFrame: through day 168 of aromatase inhibitor therapy
measure: Characterize the timing of development of muscle dysfunction following initiation of aromatase inhibitor therapy
timeFrame: through day 168 of aromatase inhibitor therapy
measure: Feasibility of repeated muscle biopsies in patients with early stage breast cancer initiating aromatase inhibitor therapy
timeFrame: through day 168 of aromatase inhibitor therapy
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: IU Simon Cancer Center
state: Indiana
Study officials:
affiliation: Indiana University
name: Tarah Ballinger, MD
role: PRINCIPAL_INVESTIGATOR
References: