Low Intensity Vibration Therapy in Reducing Musculoskeletal Dysfunction in Postmenopausal Patients with Stage I-III Breast Cancer Undergoing Aromatase Inhibitor Therapy
This phase II trial studies how low intensity vibration therapy works in reducing musculoskeletal dysfunction in patients with stage I-III breast cancer undergoing aromatase inhibitor therapy. Cancer medicine called aromatase inhibitors causes muscle weakness and bone loss in patients. Low intensity vibration may prevent the loss of muscle and bone strength in patients receiving aromatase inhibitors.
Inclusion Criteria
- Age ≥ 18 years
- Diagnosis of DCIS or stage I, II, or III breast cancer
- Planned to initiate an aromatase inhibitor * Postmenopausal defined as >= 60 years of age, bilateral oophorectomy, or age over 50 and the absence of any menstrual periods in the last 12 months, or follicle stimulating hormone (FSH) and estradiol in the menopausal range * Premenopausal patients receiving chemical ovarian suppression are allowed * Prior aromatase inhibitor use (if this is a second primary, for example) is allowed as long as it has been more than 12 months * Prior tamoxifen is allowed if switching to an aromatase inhibitor, as long as it has been 28 days between last tamoxifen dose and the baseline procedures (per the half-life of tamoxifen)
- Completion of all primary therapy for breast cancer, including surgery, radiation, and chemotherapy. Patients must be >= 21 days from chemotherapy completion and >= 14 days from radiation completion. Ongoing HER2 targeted therapy with trastuzumab, pertuzumab, or TDM1 is allowed. Neratinib, immunotherapy, or CDK4/6 inhibitor therapy is not allowed. Ongoing therapy with abemaciclib per standard of care is allowed
- Baseline T score > - 2.5 on DXA
- Body weight less than 275 lbs., as dictated by the weight limit for the LIV platforms
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of study enrollment
- Informed consent and authorization of the release of health information must be obtained according to institutional guidelines
- Physically able to stand unassisted for 10 minutes at a time
- Currently not participating in regular exercise (defined as less than 90 minutes of moderate to vigorous exercise per week measured by the Recent Physical Activity Questionnaire [RPAQ] questionnaire)
Exclusion Criteria
- Unwilling to co-enroll onto the companion FIT core study (Institutional Review Board [IRB] study #1707550885)
- Diagnosis of other disorder affecting bone function or turnover, such as Paget’s disease, renal osteodystrophy, parathyroid disorders, vitamin D deficiency/osteomalacia, chronic renal disease (Creatinine [Cr] > 1.4) * Vitamin D will be checked during screening. Patients with vitamin (Vit) D < 20 can be enrolled if supplementation is initiated per the treating physician
- Prior history of non-traumatic, fragility bone fracture
- Any muscle or neuromuscular disorder affecting muscle function, such as muscular dystrophy, myositis, or amyotrophic lateral sclerosis
- Use of bisphosphonates or denosumab within the prior 12 months
- History of retinal detachment
- Current or planned pacemaker
- Current or planned cochlear implant
- Any condition precluding power protocol participation (i.e. riding 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
- Metastatic breast cancer * History of prior treated malignancies, other than breast cancer, that are now stable, are in remission, and do not require active therapy, are acceptable
- Patients requiring chronic anticoagulation are excluded from participation in the optional muscle biopsy collection
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03712813.
PRIMARY OBJECTIVE:
I. To compare the effect of low intensity vibration (LIV) delivered for 10 minutes twice daily for 12 months on skeletal muscle function, in terms of energetic capacity measured by power generation on a stationary bicycle, among patients with early stage breast cancer planned to initiate aromatase inhibitor therapy who do not currently participate in regular exercise, compared to a wait-listed control.
SECONDARY OBJECTIVES:
I. To compare the effect of LIV versus wait-listed control upon muscle contractile properties including peak power, fatigue resistance, and recovery, measured by isokinetic knee extension.
II. To compare the effect of LIV versus wait-listed control upon body composition (lean mass, total adiposity) measured by dual x-ray absorptiometry (DXA) scan.
III. To compare the effect of LIV versus wait-listed control upon bone mineral density (T score) measured by DXA scan.
IV. To compare the effect of LIV versus wait-listed control upon muscle adipose infiltration measured by muscle density on peripheral quantitative computed tomography (CT) imaging of the proximal and distal tibia and radius.
V. To compare the effect of LIV versus wait-listed control on trabecular and cortical volumetric bone mineral density by high resolution peripheral quantitative CT of the distal and diaphyseal tibia and radius.
VI. To compare the effect of LIV versus wait-listed control on serologic markers of bone turnover, including TGF-beta and n-telopeptide (NTX).
VII. To compare the effect of LIV versus wait-listed controls upon patient reported outcome measures of fatigue (measured by the Basic Fatigue Inventory), muscle ache, and joint pain (measured by Patient Reported Outcomes-Common Terminology Criteria for Adverse Events [PRO-CTCAE]).
VIII. To describe the feasibility of LIV in this patient population, defined by patient compliance and follow up with the intervention.
EXPLORATORY OBJECTIVES:
I. To determine whether LIV preserves calstabin1 binding to RyR1, compared to wait- listed control, among patients undergoing optional muscle biopsy tissue.
II. To investigate potential biomarkers of aromatase inhibitor (AI)-induced musculoskeletal toxicity and mechanosensitivity including insulin resistance, adipokines, and sequencing measurements among patients with collection of serum samples.
III. To investigate the longitudinal effects of musculoskeletal toxicity of AI therapy using the data collected at several time points, including after completion of the intervention period (baseline, 6 months, 12 months, and 24 months).
IV. Determine the impact of AI therapy on cognitive dysfunction, and explore mediators of this relationship, including body composition, LIV use, and physical activity.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Beginning at the time of AI initiation, patients undergo low intensity vibration therapy over 10 minutes twice daily (BID) for 12 months. Patients undergo computed tomography (CT) scan and blood sample collection, dual x-ray absorptiometry scan, throughout the study and may undergo muscle biopsy on study.
ARM II: Patients receive usual care. After 12 months, patients may undergo treatment as in Arm I. Patients undergo CT scan and blood sample collection, dual x-ray absorptiometry scan, throughout the study and may undergo muscle biopsy on study.
After completion of study treatment, patients are followed up for 1 year.
Trial PhasePhase II
Trial Typesupportive care
Lead OrganizationIndiana University/Melvin and Bren Simon Cancer Center
Principal InvestigatorTarah J. Ballinger
- Primary IDIUSCC-0680
- Secondary IDsNCI-2018-02759
- ClinicalTrials.gov IDNCT03712813