Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Musculoskeletal Diseases

Nervous System Diseases

Breast Neoplasms

Pain

Arthralgia

Joint Diseases

Neurologic Manifestations

All Drugs and Chemicals

Other Dietary Supplements

Aromatase Inhibitors

Omega 3 Fatty Acid

No supplement but will be offered supplements after finishing the study

1 ounce of Tart Cherry Concentrate (King Orchard) mixed with 8 ounces of water daily for 12 weeks

Tart Cherry

2 capsules of Omega 3 FA (Fish Oil) (Nordic Naturals Ultimate Omega) \[650 mg EPA and 450 mg DHA per capsule\] daily for 12 weeks

Omega 3 FA (Fish Oil)

Clinical Trial Navigator

Clinical Trial Recruitment Navigator

Philip Chang, MD

Arash Asher, MD

Sarah Valdez

David Chan, MD

Vanessa Dickey, MD

Hugo Hool, MD

Syed Jilani, MD

Thomas Lowe, MD

Swati Sikaria, MD

Philip Chang, DO

Both Tart Cherry and Omega 3 FAs have better side effect profiles compared to other commonly used medications for AIMSS, such as nonsteroidal anti-inflammatories, steroids, and serotonin norepinephrine reuptake inhibitors. Additionally, in our clinics the investigators often find that patients tend to be more receptive to taking a supplement as opposed to an additional medication. Further, both Tart Cherry concentrate and fish oil have beneficial properties for helping with joint stiffness in general, in addition to other health issues like insomnia.

There is some evidence in mouse models that when given together, these supplements may have an even greater anti-inflammatory effect than when taken separately. Although to our knowledge, no human studies have tested this hypothesis. This study has been designed to test the hypothesis that Tart Cherry and fish oil when given in combination over a 12-week period could produce beneficial changes in arthritis symptoms when compared to a control group in an obese breast cancer population experience AIMSS and on an AI. Secondary outcomes to be assessed include pain, functional performance, quality of life and cognition.

Tart Cherry and Omega-3's for Aromatase Inhibitor Musculoskeletal Symptoms

An Open Label, Randomized, Waitlist Controlled Trial of Tart Cherry and Omega-3's for Aromatase Inhibitor Musculoskeletal Symptoms

Changes in arthritis symptoms will be assessed via the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The WOMAC Pain score ranges from 0% to 100% with higher scores indicating greater difficulty with activities of daily living.

Changes in nociplastic pain will be measured by composite score on Symptom Severity Scale. The Symptom Severity Scale ranges from 0-12 with higher scores equating to increased nociplastic pain.

Changes in nociplastic pain will be measured by composite score on Widespread Pain Index. The Widespread Pain Index score ranges from 0-19 with higher scores equating to increased nociplastic pain.

Functional Performance will be measured by changes in the Patient-Reported Outcomes Measurement Information System (PROMIS) Cancer 3D Function Profile. The PROMIS Cancer 3D Function Profile has 3 subgroups including Physical Function, Fatigue and Social Participation. The Physical Function score ranges from 5-30 with higher scores equating to better function. The Fatigue score ranges from 3-15 with higher scores equating to less fatigue. The Social Participation score ranges from 3-15 with higher scores equating to worse social participation.

Quality of Life will be measured by changes in the Patient-Reported Outcomes Measurement Information System (PROMIS) PROMIS-29+2. The PROMIS-29+2 has 8 subgroups including physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles, pain interference and cognitive function. All subgroups are scored from 4-20 except for cognitive function which is scored from 2-10.

Cognition will be measured by changes in the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function 8a Short Form. The PROMIS Cognitive Function Short Form 8a score ranges from 8 to 40 with higher scores indicating better cognitive function.

The Cherry Marketing Institute

Philip Chang

Sponsor-Investigator

Breast Diseases

Skin Diseases

Menopause

Tarah Ballinger, MD

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

Serum blood samples will be collected to measure markers of bone turnover and to perform a serum TGF-β assay. Samples will be collected at baseline and within 14 days of day 168 of aromatase inhibitor (AI) treatment

Skeletal muscle tissue will be collected and used to compare relative calstabin1 to RyR1 and RyR1 oxidation before and after exposure to aromatase inhibitor (AI) treatment. One sample will be stored for future research relating to aromatase inhibitor-induced muscle weakness including proteomic research. Four core needle samples will be taken from the quadriceps muscle at baseline and within 14 days of day 168 of AI treatment.

Effects of Aromatase Inhibitor Therapy on Muscle Function

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

Changes in calstabin1 binding to RyR1 channels in skeletal muscle of breast cancer patients pre and post exposure to adjuvant aromatase inhibitor therapy

To estimate changes in RyR1 oxidation in skeletal muscle of breast cancer patients, pre- and post- exposure to adjuvant aromatase inhibitor therapy

To explore the relationship between changes in RyR1 biochemistry and measures of muscle function, including muscle power as measured by isokinetic dynamometry

To explore the relationship between markers of bone turnover and changes in RyR1 biochemistry (calstabin binding to RyR1)

To explore the relationship between markers of bone turnover and changes in muscle function in terms of muscle power assessed by isokinetic dynamometry

To better characterize the timing of development of muscle dysfunction following initiation of aromatase inhibitor therapy, in terms muscle power measured by isokinetic dynamometry

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

Tarah J Ballinger, MD

Assistant Professor of Clinical Medicine

Behaviors and Mental Disorders

Quality of Life

After completing the baseline tests, participants in exercise group were instructed to attend 90-minute, supervised Baduanjin exercise 2 times per week. The Baduanjin intervention used the standardized Baduanjin training program, designed by the General Administration of Sports of China. Two senior Baduanjin teachers from Guangzhou Sports University conducted the training.

Participants assigned to the wait-list control were told to continue performing their usual care and daily activities, and to refrain from doing any Baduanjin exercise.

After their post-assessment they were able to attend the Baduanjin classes.

Baduanjin exercise

Kun Wang

A 12-week randomized controlled trail was conducted in 72 Chinese breast cancer survivors who had received aromatase inhibitors treatment for more than 6 months. All participants were assigned to either 12 weeks of Baduanjin classes which involved to two 90-minute sessions per week or a wait-list control. Participants completed fitness assessments, measurements of lipopolysaccharide-stimulated production of proinﬂammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-1β(IL-1β) ,C-reactive protein (CRP) ，BMI，BMD and questionnaires to measure QoL, fatigue, sleep quality, Aromatase Inhibitor-Induced Arthralgia, symptoms of climacteric syndrome were completed at baseline and 3 months.

Evaluating the Impact of Baduanjin Exercise Intervention on Quality of Life in Breast Cancer Survivors Receiving Aromatase Inhibitor Therapy

Evaluating the Impact of Baduanjin Exercise Intervention on Quality of Life in Breast Cancer Survivors Receiving Aromatase Inhibitor Therapy：: A Pilot Study

European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 version 3 (EORTC QLQ-C30)

Upper strength: hand grip (measured by a dynamometer; the average of 3 readings) lower limb strength：sit-to-stand (measured as number of reps in a 30-s period)

Test of scratching his back and Sit in the chair and reach

Guangzhou Sport University

Guangdong Provincial People's Hospital

Professor

Home-based walking intervention, wearing a wrist worn activity tracker, for 24 weeks + standard adjuvant AI therapy

Physical activity according to standard recommendations, wearing a wrist worn activity tracker (with no feedback about performed activity), for 24 weeks + standard adjuvant AI therapy

Home-based walking intervention, wearing a wrist worn activity tracker, for 24 weeks

Activity program

Control

Friedemann Honecker, MD

Nicolette Hoefnagels, MSc

The primary aim of the trial is to investigate if a simple outdoor walking intervention, which is practicable under real-life conditions, beginning at the start of adjuvant aromatase inhibitor (AI) therapy, can prevent the occurrence of muscle or joint pain/stiffness in breast cancer patients.

After tumor removal, patients with hormone receptor positive breast cancer tumors often receive adjuvant endocrine treatment, with the use of an aromatase inhibitor (AI) being standard of care in the population of postmenopausal women. Common side effects of AI therapy are joint pain, muscle pain, stiffness, fatigue, hot flashes, and weight gain. Arthralgia and/or myalgia can result in lower physical activity and can negatively influence quality of life (QoL). In addition, muscle or joint pain/stiffness are among the main reasons for non-compliance and discontinuation of AI therapy. Because AI therapy is usually administered for 5 and sometimes even 10 years, this is a major clinical challenge.

For breast cancer patients undergoing AI therapy, physical activity can provide potential benefit by reducing muscle/joint pain and fatigue and can thus improve QoL. The preventive effect of physical activity on AI side effects, however, remains elusive. In addition, activity programs to reduce AI side effects have so far mostly been rather complex. The primary aim of the trial is to investigate if a simple outdoor walking intervention, which is practicable under real-life conditions, beginning at the start of adjuvant AI therapy, can prevent the occurrence of muscle or joint pain/stiffness in breast cancer patients.

Furthermore, this trial will assess the effect of physical activity on symptom burden in general and quality of life in patients receiving adjuvant AI therapy. During the follow-up phase, the trial will assess whether this intervention leads to a sustained change in lifestyle regarding activity, less pain, and better treatment adherence in the intervention group.

1. Home-based walking intervention for 24 weeks + standard adjuvant AI therapy
2. Physical activity according to standard recommendations for 24 weeks + standard adjuvant AI therapy

Activity Program During Aromatase Inhibitor Therapy

A 24 Weeks Activity Program in Patients With Early Breast Cancer Receiving Aromatase Inhibitor Therapy. A Multicenter Randomized Phase III Trial

Muscle or joint pain/stiffness will be assessed at baseline, 3, 9, 12, 15, 18, 21, 24 weeks after randomization by the BPI-SF questionnaire.

The BPI-SF is a 14-item self-administered questionnaire which is routinely used in clinical trials to assess pain severity and pain interference with daily activities in patients with cancer. Pain severity is assessed by four items including pain at its "worst", "least", "average" in the last 24 hours and "now" (current pain), each item being rated on a 0-10 scale.

Fatigue will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Physical scale will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Role scale will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Emotional scale will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Cognitive scale will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Nausea/vomiting will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Pain will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Global health status will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Dyspnoea will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Insomnia will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Appetite loss will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Constipation will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Diarrhoea will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Financial difficulties will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0.

Hot flashes will be assessed at baseline, during intervention phase and during follow-up phase via the item 37 of the EORTC QLQ BR-23.

Severity of muscle or joint pain/stiffness will be measured by the four BPI pain severity items. Pain interference will be calculated as the mean of the seven interference items.

During trial intervention phase, daily steps will be measured by a wrist worn activity tracker.

Adherence will be assessed by patient self-report (diary).

Adherence will be assessed by patient self-report (questionnaire completed at visits).

Swiss Group for Clinical Cancer Research

Adenocarcinoma

Antineoplastic Agents

Bone Density Conservation Agents

Estrogens

Anastrozole

Zoledronic Acid

Denosumab

Progesterone

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.

Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.

Eligible participants who completed the open-label phase could be enrolled into the zoledronic acid substudy and randomized to receive a single 5 mg intravenous dose of zoledronic acid 8 months after the last open-label dose of denosumab.

Eligible participants who completed the open-label phase could be enrolled into the zoledronic acid substudy and randomized to receive standard of care 8 months after the last open-label dose of denosumab.

Placebo

An approved non-steroidal aromatase inhibitor therapy (eg, anastrazole) in the adjuvant setting

Non-steroidal aromatase inhibitor therapy

5 mg zoledronic acid administered at a constant infusion rate

Standard of care (SoC) as recommended by the treating physician, depending on individual factors such as bone density, lifestyle recommendations by the Investigator such as diet, physical activities and sun exposure, as well as local treatment standards.

Standard of Care

The purpose of this study is to determine whether denosumab compared to placebo, will reduce the rate of first clinical fracture in women with non-metastatic breast cancer receiving (non-steroidal) aromatase inhibitor therapy.

Participants will remain on treatment until the required number of events (where an event is defined as first clinical fracture) is reached and all participants have had the opportunity to receive a minimum of at least 2 doses of study drug, whichever occurs later. The primary analysis data cut-off date (PADCD) is defined as the time at which the required number of events is reached and all participants have had the opportunity to receive at least 2 doses of study drug. When the PADCD is reached, all participants will discontinue study drug.

Following the study PADCD, participants will be followed every 12 months starting from their last study visit until a maximum of 66 months after PADCD.

After approval of Amendment 4, willing and eligible participants randomized to placebo during the double-blind phase may participate in an open-label phase (OLP) and receive denosumab 60 mg Q6M for up to 36 months (maximum of 7 doses).

After approval of Amendment 6 in 2019 a zoledronic acid (ZA) substudy was added to the protocol. Willing and eligible participants who participated in the OLP of the study and completed open-label denosumab may opt in to this ZA substudy and either receive a single dose of ZA (Therapy Arm), or be managed according to the current standard of care for this patient population (Control Arm).

Study to Determine Treatment Effects of Denosumab in Patients With Breast Cancer Receiving Aromatase Inhibitor Therapy

A Randomised, Double-Blind, Placebo-Controlled, Multi-Centre Phase 3 Study to Determine the Treatment Effect of Denosumab in Subjects With Non-Metastatic Breast Cancer Receiving Aromatase Inhibitor Therapy.

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

The time to first on-study clinical fracture was defined as the number of days from randomization to the date of the x-ray confirming the clinical fracture. A clinical fracture is any clinically evident fracture with associated symptoms and confirmed by x-ray. Participants who died or withdrew without experiencing a clinical fracture were censored at the date of last contact or study termination whichever was earlier.

Bone mineral density was assessed by dual x-ray absorptiometry.

Assessment of vertebral fractures was performed by an expert radiologist at the central imaging center using a semiquantitative grading scale: Grade 1, 20% to 25% reduction in vertebral height (anterior, middle, or posterior); Grade 2, 25% to 40% reduction in height; Grade 3, greater than 40% reduction in height.

A new vertebral fracture was defined as a fracture in a previously undeformed vertebrae including new compression fractures, defined as those compression fractures having a decrease in total anterior or posterior height of at least 25% from baseline. New vertebral fractures includes morphometric vertebral fractures identified from on study x-rays and clinical vertebral fractures confirmed by x-rays.

Assessment of vertebral fractures was performed by an expert radiologist at the central imaging center using a semiquantitative grading scale: Grade 1, 20% to 25% reduction in vertebral height (anterior, middle, or posterior); Grade 2, 25% to 40% reduction in height; Grade 3, greater than 40% reduction in height.

A new vertebral fracture was defined as a fracture in a previously undeformed vertebrae including new compression fractures, defined as those compression fractures having a decrease in total anterior or posterior height of at least 25% from baseline. New vertebral fractures includes morphometric vertebral fractures identified from on study x-rays and clinical vertebral fractures confirmed by x-rays. Worsening of pre-existing fractures was defined as an increase in fracture severity of at least 1 grade on the semiquantitative scale.

DFS was defined as the time interval from the randomization date to the date of first evidence of local or distant metastases, contra-lateral breast cancer, secondary carcinoma, or death from any cause (whichever occurred first). Participants last known to be alive, who did not experience recurrence of disease, were censored at their last contact date or at the data cut-off date whichever came first.

BMFS was defined as the time interval from randomization to first occurrence of bone metastasis or death from any cause, whichever comes first. Participants last known to be alive, who did not experience bone metastasis, were censored at their last assessment (i.e., bone scan) date or at the last contact date, whichever comes first.

OS was defined as the time from randomization to death from any cause.

Austrian Breast and Colorectal Cancer Study Group

Amgen

All randomized participants who received \>1 dose of treatment; participants were analyzed according to the actual treatment received in double-blind phase. 9 participants randomized to the placebo in the DB phase incorrectly received denosumab. Per protocol, only AEs of special interest and SAEs were collected in the open-label phase. MedDRA 17.1 used in double-blind phase and 24.0 in the open-label phase.

Participants received the matching placebo SC Q6M in the double-blind phase. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.

Double-blind Phase: Placebo

Participants received 60 mg denosumab SC Q6M in the double-blind phase. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.

Double-blind Phase: Denosumab

Participants who received the matching placebo during the double-blind phase, who continued into the open-label phase where they received denosumab 60 mg SC Q6M for up to a maximum of 7 additional doses.

Open-label Phase: Placebo/Denosumab

Participants who received denosumab during the double-blind phase, who continued into the open-label phase where they received denosumab 60 mg SC Q6M for up to a maximum of 7 additional doses.

Open-label Phase: Denosumab/Denosumab

Participants randomized to receive the matching placebo subcutaneously (SC) once every 6 months (Q6M) in the double-blind phase. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.

Participants randomized to receive 60 mg denosumab SC once Q6M in the double-blind phase. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Major Academic Center

Other Center

Stratification Factor: Type of Hospital

Stratification Factor: Prior Aromatase inhibitor Use

T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults.

T-score ≥ -1.0: BMD is considered normal.

T-score \< -1.0: Low BMD.

Stratification Factor: Total Lumbar Spine BMD T-score

Study Director

The efficacy clinical hypothesis is that denosumab, when administered subcutaneously at a dose of 60 mg every 6 months, will be considered efficacious in patients with non-metastatic breast cancer receiving AIT if the rate of first clinical fracture in denosumab-treated patients is lower than that in placebo-treated patients. It is anticipated that denosumab will reduce the rate by 30% compared with placebo (ie, the true hazard ratio of denosumab compared with placebo is 0.70).

Full Analysis Set: all randomized participants

Time to First Clinical Fracture

BMD Analysis Set: all participants with evaluable lumbar spine BMD values at Baseline and Month 36

Percent Change From Baseline in Total Lumbar Spine Bone Mineral Density (BMD) at Month 36 at Pre-selected Sites

BMD Analysis Set: all participants with total hip BMD evaluable values at Baseline and Month 36

Percent Change From Baseline in Total Hip BMD at Month 36 at Pre-selected Sites

BMD Analysis Set: all participants with evaluable femoral neck BMD values at Baseline and Month 36

Percent Change From Baseline in Femoral Neck BMD at Month 36 at Pre-selected Sites

Vertebral Fracture Analysis Set: all participants with a Baseline and at least one post-baseline vertebral x-ray prior to or at Month 36

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tart Cherry and Omega-3's for Aromatase Inhibitor Musculoskeletal Symptoms	NCT06123286	Breast Cancer Aromatase Inhib... Joint Pain	Tart Cherry Omega 3 FA (Fis...	18 Years -	Cedars-Sinai Medical Center
Effects of Aromatase Inhibitor Therapy on Muscle Function	NCT03581552	Breast Cancer Breast Cancer F...		18 Years -	Indiana University
Evaluating the Impact of Baduanjin Exercise Intervention on Quality of Life in Breast Cancer Survivors Receiving Aromatase Inhibitor Therapy	NCT03162133	Breast Cancer S...	Baduanjin exerc...	18 Years - 70 Years	Guangdong Provincial People's Hospital
Evaluating the Impact of Baduanjin Exercise Intervention on Quality of Life in Breast Cancer Survivors Receiving Aromatase Inhibitor Therapy	NCT03162133	Breast Cancer S...	Baduanjin exerc...	18 Years - 70 Years	Guangdong Provincial People's Hospital
Activity Program During Aromatase Inhibitor Therapy	NCT03786198	Early Breast Ca...	Activity progra... Control	18 Years -	Swiss Group for Clinical Cancer Research
Study to Determine Treatment Effects of Denosumab in Patients With Breast Cancer Receiving Aromatase Inhibitor Therapy	NCT00556374	Breast Cancer	Placebo Denosumab Non-steroidal a... Zoledronic Acid Standard of Car...	45 Years - 100 Years	Amgen
Activity Program During Aromatase Inhibitor Therapy	NCT03786198	Early Breast Ca...	Activity progra... Control	18 Years -	Swiss Group for Clinical Cancer Research

Spots Global Cancer Trial Database for aromatase inhibitor therapy