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Randomized Double-Blind Placebo Controlled Study of Subcutaneous Testosterone in the Adjuvant Treatment of Postmenopausal Women With Aromatase Inhibitor Induced Arthralgias

Phase 3
18 Years
Not Enrolling
Arthralgia, Breast Cancer, Hot Flashes, Musculoskeletal Complications, Sexual Dysfunction

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Trial Information

Randomized Double-Blind Placebo Controlled Study of Subcutaneous Testosterone in the Adjuvant Treatment of Postmenopausal Women With Aromatase Inhibitor Induced Arthralgias



- To determine whether testosterone will reduce aromatase inhibitor (AI)-induced
arthralgia and associated joint symptoms.


- To explore whether testosterone will have an acceptable safety and tolerability
profile, with particular reference to androgenic adverse events including acne,
hirsutism, and alopecia.

- To explore whether testosterone will reduce AI-induced arthralgias and associated joint
symptoms and their interference with activity. (Ancillary)

- To explore whether testosterone will reduce the incidence of hot flashes. (Ancillary)

- To explore whether testosterone will modify libido or change quality of life.

- To explore whether identified single nucleotide polymorphisms (SNPs), that were
associated with more AI-associated arthralgias in a previous prospective trial, are
more commonly seen in the patients entered into the present clinical trial, than are
observed in the normal population. (Ancillary)

OUTLINE: This is a multicenter study. Patients are stratified according to baseline pain
score (5-6 vs 7-10) and age in years (< 50 vs 50-60 vs > 60). Patients are randomized to 1
of 2 treatment arms.

- Arm I: Patients receive testosterone transdermally on day 1 and then at 3 months.

- Arm II: Patients receive placebo transdermally on day 1 and then at 3 months. Blood
samples are collected at baseline and during treatment for correlative studies.

Patients complete the Hot Flash Diary daily for 2 months and the Profile of Mood States
(POMS), the Hot Flash Related Daily Interference Scale (HFRDIS), the Modified Brief Pain
Inventory, and the Menopause Specific Quality of Life Questionnaire (MENQOL) at baseline,
after completion of treatment, and at 6 months.

After completion of study treatment, patients are followed up for 6 months.

Inclusion Criteria


- Women who have undergone a total mastectomy or breast-conserving surgery for primary
breast cancer +/-chemotherapy and +/-radiotherapy

- Receiving anastrozole (1 mg) or letrozole (2.5 mg) orally once a day, for ≥ 21 days
prior to registration

- Must have BOTH estrogen receptor-positive (ER+) and progesterone receptor-positive
(PR+) tumors and BOTH must be ≥ 30% positive

- ≥ 5/10 arthralgia (in hands, wrist, knees, or hips) while being treated with
anastrozole or letrozole which is felt by the patient to be caused by their aromatase
inhibitor, as measured by verbally addressing the following question: "Please rate
your pain by picking a number, from 0 to 10 (0 being none and 10 being as bad as you
can imagine) that best describes your pain from your aromatase inhibitor breast
cancer medication on AVERAGE, over the past week."

- No presence of residual or recurrent cancer (locally or metastatic)


- Body Mass Index (BMI) between 18 and 32 kg/m²

- Women who are postmenopausal by surgery, radiotherapy, or presence of natural
amenorrhea ≥ 12 months

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) ≤
1.5 times upper limit of normal (ULN)

- ECOG Performance Status (PS) 0, 1, or 2

- Serum creatinine ≤1.5 times ULN

- Hemoglobin > 11 g/dL

- White blood cell (WBC) > 3,000/mm³

- Platelets > 100,000/mm³

- No medical situations that would alter the laboratory values since they were done

- Ability to complete questionnaire(s) by themselves or with assistance

- Willing to provide informed written consent

- Willing to return to an Alliance enrolling institution for follow-up

- Willing to provide blood samples for correlative research purposes

- No diabetes mellitus or glucose intolerance, defined as a fasting glucose > 125 mg/dL

- No history of coronary artery disease (angina or myocardial infarction)

- No known hypersensitivity to any component of testosterone

- No history of a deep venous thrombosis or a thromboembolism


- See Disease Characteristics

- Patients may, or may not, be taking non-opiod analgesics

- No patients on hormone-replacement therapy (HRT) ≤ 4 weeks before prior to

- No prolonged systemic corticosteroid treatment, except for topical applications
(e.g., for rash), inhaled sprays (e.g., for obstructive airway diseases), eye drops,
or local injections (e.g., intra-articular)

- Short duration (< 2 weeks) of systemic corticosteroids is allowed (e.g., for
chronic obstructive pulmonary disease), but not within 30 days prior to

- Not receiving any other investigational agent

- No concurrent use of the aromatase inhibitor exemestane

- No concurrent radiation therapy or chemotherapy

- No current or planned use of cyclosporine, anticoagulants, oxyphenbutazone, insulin,
or tamoxifen

Type of Study:


Study Design:

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care

Outcome Measure:

The intra-patient change in joint pain at 3 months from baseline as measured by the Brief Pain Inventory for aromatase-inhibitor arthralgias (BPI-AIA)

Safety Issue:


Principal Investigator

Charles L. Loprinzi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

North Central Cancer Treatment Group



Study ID:




Start Date:

April 2012

Completion Date:

Related Keywords:

  • Arthralgia
  • Breast Cancer
  • Hot Flashes
  • Musculoskeletal Complications
  • Sexual Dysfunction
  • hot flashes
  • musculoskeletal complications
  • sexual dysfunction
  • estrogen receptor-positive breast cancer
  • progesterone receptor-positive breast cancer
  • arthralgia
  • stage IA breast cancer
  • stage IB breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • Arthralgia
  • Breast Neoplasms
  • Sexual Dysfunctions, Psychological
  • Hot Flashes