Exercise to Prevent Aromatase Inhibitor Side Effects in Breast Cancer Patients

NCT ID: NCT01954706

Last Updated: 2015-11-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

5 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-30

Study Completion Date

2015-09-30

Brief Summary

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Hormone receptor-positive tumors are the most common breast cancers in postmenopausal women, and drug therapies, which block the production or effects of estrogen, are the mainstay of treatment in these patients. Due to their effectiveness in postmenopausal women, aromatase inhibitors (AIs) are the standard of care for long-term estrogen suppression in these patients. Estrogen deficiency, however, results in multiple side effects. Some of the most common side effects in women taking AIs are joint and muscle aches, which promote physical deconditioning. Because of the long term use of AIs in postmenopausal breast cancer patients and the improvements in cancer-related outcomes that are observed with their use, identifying methods to reduce these side effects to maintain adherence to treatment is important. Exercise interventions in breast cancer patients also improve quality of life and reduce fatigue. Understanding the role of exercise in AI side effect prevention will allow us to translate these findings into therapy guidelines.

Detailed Description

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Breast cancer is the most common malignancy in women in the United States and is the second leading cause of cancer deaths. In 2013, an estimated 230,000 women in the United States will be diagnosed with invasive breast cancer and approximately 40,000 with die.1 Women with breast cancer frequently experience significant functional and metabolic declines during and after treatment due to cancer-related fatigue (CRF), stress and depression.2,3 Cancer-related fatigue is associated with side effects from treatment, pain, functional disability, sleep disturbances, mood disturbances and co-morbid conditions.4 Patients with CRF have declines in physical activity and function, which significantly impacts quality of life (QOL).5 The mechanisms underlying functional declines and fatigue in breast cancer patients are likely multifactorial, but deconditioning, sarcopenia, increases in inflammatory cytokines, insulin resistance, and changes in muscle and fat metabolism seem to play important roles.4,6

Hormone receptor-positive tumors are the most common breast cancers in postmenopausal women, and endocrine therapies, which block the production or effects of estrogen, are the mainstay of treatment in these patients. Due to their superior efficacy in postmenopausal women, aromatase inhibitors (AIs) are the standard of care for long-term estrogen suppression in these patients.7 Estrogen deprivation, however, results in multiple side effects which may worsen fatigue and the functional and metabolic declines associated with cancer treatment.8 Some of the most common side effects in women taking AIs are musculoskeletal symptoms, including arthralgias and myalgias, which promote deconditioning and sarcopenia and their associated side effects.9 Because of the prolonged use of AIs in postmenopausal breast cancer patients and the improvements in cancer-related outcomes that are observed with their use, great efforts are taken to reduce AI induced musculoskeletal symptoms (AIMSS) to maintain adherence to treatment. While multiple strategies are used to manage AIMSS, current therapies mainly focus on interventions in patients who develop symptoms (tertiary prevention) rather than primary prevention.9 Exercise interventions in breast cancer patients also improve QOL, decrease fatigue, and increase physical function and strength.10,11 Understanding the role of exercise in AI side effect prevention will allow us to translate these findings into therapy guidelines.

Conditions

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Breast Cancer Sarcopenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Structured Exercise

Structured and supervised aerobic and resistance training 2 times per week

Group Type EXPERIMENTAL

Structured Exercise

Intervention Type OTHER

Structured and supervised aerobic and resistance training 2 times per week

Usual Care

Subjects will be counseled on American Cancer Society and American College of Sports Medicine physical activity and nutritional guidelines at the initiation of the study. Study participants will be contacted by a physician or nurse on weeks 2, 6, 10, and 14 to provide support and encouragement to patients.

Group Type ACTIVE_COMPARATOR

Usual Care

Intervention Type OTHER

Subjects will be counseled on American Cancer Society and American College of Sports Medicine physical activity and nutritional guidelines at the initiation of the study. Study participants will be contacted by a physician or nurse on weeks 2, 6, 10, and 14 to provide support and encouragement to patients.

Interventions

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Structured Exercise

Structured and supervised aerobic and resistance training 2 times per week

Intervention Type OTHER

Usual Care

Subjects will be counseled on American Cancer Society and American College of Sports Medicine physical activity and nutritional guidelines at the initiation of the study. Study participants will be contacted by a physician or nurse on weeks 2, 6, 10, and 14 to provide support and encouragement to patients.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* At least mild fatigue in 2 of the 4 areas of the Piper Fatigue Scale (score ≥ 1-3)
* Completion of standard surgery +/- chemotherapy for breast cancer (may undergo radiation therapy during study)
* 25-OH vitamin D \> 20 ng/ml
* Histological evidence of stage I-III hormone receptor-positive breast cancer
* Body Mass Index \>/=18 and \<50 kg/m2
* 40-80 years of age
* Non-smoking (non smoking for at least 12 months: cigarettes, cigars, pipes
* Menopause over one year (absence of menses for 12 months or greater)
* Sedentary (exercise no \>60 min 2 times/week)

Exclusion Criteria

* Taking oral steroids, warfarin, or other medications interfering with fat metabolism that may not be safely discontinued temporarily for specific produces (i.e. for 72 hours prior)
* Symptomatic heart disease, coronary artery disease, congestive heart failure, or uncontrolled hypertension (systolic blood pressure over 180 mm HG)unless medically stabilized
* Participant is, in the opinion of the investigator, unable to adhere to the study protocol due to medical or orthopedic conditions that limit ability to exercise or travel to the Baltimore VA for protocol procedures
* Chronic pulmonary disease (on supplemental O2)
* Abnormal renal function (BUN above 40 mg/dl, Cr above 1.3 mg/dl, CrCl\<60mg/dl)
* Unstable lymphedema
* Evidence of cancer metastases or recurrence
* Anemia HCT below 30 mg/dl, platelets below 80,000/cm3
* Type 1 diabetes; insulin treatment for diabetes, poorly controlled diabetes, HgA1c\>10%
* Abnormal response to exercise test (ST segment depression greater than 2mm, chest pain, significant arrhythmias, extreme shortness of breath, cyanosis, exercising BP above 240/120 mm HG, or other contraindications to exercise) confirmed with further diagnostic evaluations.
* Abnormal liver function
* Untreated dyslipidemia with National Cholesterol ATPIII 10 year cardiac risk score greater than 10% (www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04.htm)
* Metal implants or devices (i.e. pacemaker) if undergoing CT scan
* History of seizures or taking anti-seizure or anti convulsion medication
* Allergic to lidocaine
* Mini-mental state examination below 24, dementia, or unstable clinical depression by exam
Minimum Eligible Age

40 Years

Maximum Eligible Age

80 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Baltimore VA Medical Center

FED

Sponsor Role lead

Responsible Party

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Susan B. Kesmodel, MD

Assistant Professor of Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Susan Kesmodel, MD

Role: PRINCIPAL_INVESTIGATOR

Baltimore VAMC

Locations

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Baltimore VA Medical Center

Baltimore, Maryland, United States

Site Status

Countries

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United States

References

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Society AC. Cancer Facts & Figures 2013. Atlanta: American Cancer Society 2013.

Reference Type BACKGROUND

Thomson CA, Thompson PA, Wright-Bea J, Nardi E, Frey GR, Stopeck A. Metabolic syndrome and elevated C-reactive protein in breast cancer survivors on adjuvant hormone therapy. J Womens Health (Larchmt). 2009 Dec;18(12):2041-7. doi: 10.1089/jwh.2009.1365.

Reference Type BACKGROUND
PMID: 20044868 (View on PubMed)

Curt GA. Impact of fatigue on quality of life in oncology patients. Semin Hematol. 2000 Oct;37(4 Suppl 6):14-7. doi: 10.1016/s0037-1963(00)90063-5.

Reference Type BACKGROUND
PMID: 11068951 (View on PubMed)

Cramp F, Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD006145. doi: 10.1002/14651858.CD006145.pub2.

Reference Type BACKGROUND
PMID: 18425939 (View on PubMed)

Braithwaite D, Satariano WA, Sternfeld B, Hiatt RA, Ganz PA, Kerlikowske K, Moore DH, Slattery ML, Tammemagi M, Castillo A, Melisko M, Esserman L, Weltzien EK, Caan BJ. Long-term prognostic role of functional limitations among women with breast cancer. J Natl Cancer Inst. 2010 Oct 6;102(19):1468-77. doi: 10.1093/jnci/djq344. Epub 2010 Sep 22.

Reference Type BACKGROUND
PMID: 20861456 (View on PubMed)

Berger AM, Gerber LH, Mayer DK. Cancer-related fatigue: implications for breast cancer survivors. Cancer. 2012 Apr 15;118(8 Suppl):2261-9. doi: 10.1002/cncr.27475.

Reference Type BACKGROUND
PMID: 22488700 (View on PubMed)

Collado-Hidalgo A, Bower JE, Ganz PA, Cole SW, Irwin MR. Inflammatory biomarkers for persistent fatigue in breast cancer survivors. Clin Cancer Res. 2006 May 1;12(9):2759-66. doi: 10.1158/1078-0432.CCR-05-2398.

Reference Type BACKGROUND
PMID: 16675568 (View on PubMed)

Lin NU, Winer EP. Advances in adjuvant endocrine therapy for postmenopausal women. J Clin Oncol. 2008 Feb 10;26(5):798-805. doi: 10.1200/JCO.2007.15.0946.

Reference Type BACKGROUND
PMID: 18258989 (View on PubMed)

Dent SF, Gaspo R, Kissner M, Pritchard KI. Aromatase inhibitor therapy: toxicities and management strategies in the treatment of postmenopausal women with hormone-sensitive early breast cancer. Breast Cancer Res Treat. 2011 Apr;126(2):295-310. doi: 10.1007/s10549-011-1351-3. Epub 2011 Jan 20.

Reference Type BACKGROUND
PMID: 21249443 (View on PubMed)

Gaillard S, Stearns V. Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management. Breast Cancer Res. 2011 Mar 14;13(2):205. doi: 10.1186/bcr2818.

Reference Type BACKGROUND
PMID: 21457526 (View on PubMed)

Winters-Stone KM, Dobek J, Bennett JA, Nail LM, Leo MC, Schwartz A. The effect of resistance training on muscle strength and physical function in older, postmenopausal breast cancer survivors: a randomized controlled trial. J Cancer Surviv. 2012 Jun;6(2):189-99. doi: 10.1007/s11764-011-0210-x. Epub 2011 Dec 23.

Reference Type BACKGROUND
PMID: 22193780 (View on PubMed)

Other Identifiers

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P30AG028747

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HP-00056384

Identifier Type: -

Identifier Source: org_study_id