Testosterone in Treating Postmenopausal Patients With Arthralgia Caused by Adjuvant Aromatase Inhibitor Treatment

This is a randomized, placebo-controlled, phase III trial evaluating subcutaneous
testosterone for the alleviation of aromatase inhibitor induced arthralgia. A parallel group
design will be utilized for this two-arm study: subcutaneous testosterone vs. placebo.
Patients are stratified according to baseline pain score (5-6 vs. 7-10) and age (< 50 vs.
50-60 vs. > 60). The primary objective is to determine whether testosterone will reduce
AI-induced arthralgia and associated joint symptoms. The secondary objective is to explore
whether testosterone will have an acceptable safety and tolerability profile, with particular
reference to androgenic adverse events including acne, hirsutism, and alopecia.

Patients are followed up to six months as defined in the protocol.

Inclusion Criteria:

1. Age ≥ 18 years

2. Receiving anastrozole (1mg) or letrozole (2.5 mg) orally once a day, for ≥ 21 days
prior to registration and plan to continue it throughout the duration of study

3. Body Mass Index (BMI) between 18 and 35 kg/m^2

4. Women who have undergone a total mastectomy or breast conserving surgery for primary
breast cancer +/-chemo, +/-radiotherapy.

5. Must have BOTH ER and PR receptor-positive tumors and BOTH must be ≥26% positive.
Alternatively, if ER and PR are determined by Allred score, the score needs to be 5 or
higher

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

7. ≥ 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 defined in the protocol. Note: Patients may, or may not, be taking
non-opioid analgesics

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

9. ECOG Performance Status (PS) 0, 1 or 2

10. Willing to provide informed written consent

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

12. Willing to provide blood samples for correlative research purposes

13. Laboratory values prior to registration as defined in the protocol:

1. Creatinine ≤1.5 x ULN

2. Hemoglobin > 11 g/dL

3. WBC > 3.0

4. Platelet Count > 100,000

5. SGOT (AST) ≤ 1.5 x ULN

Exclusion Criteria:

1. Presence of residual or recurrent cancer (locally or metastatic)

2. Diabetes mellitus or glucose intolerance, defined as a fasting glucose >125 mg/dL

3. History of coronary artery disease (angina or myocardial infarction)

4. Patients on hormone replacement therapy (HRT) ≤ 4 weeks prior to registration. This
includes the use of vaginal estrogen therapy.

5. Known hypersensitivity to any component of testosterone.

6. Prolonged systemic corticosteroid treatment, except for topical applications (e.g. for
rash), inhaled sprays (e.g. for obstructive airway diseases), eye drops or local
insertion (e.g. intra-articular). Note: Short duration (< 2 weeks) of systemic
corticosteroids is allowed (e.g. for chronic obstructive pulmonary disease) but not
within 30 days prior to registration.

7. Receiving any other investigational agent

8. History of a deep venous thrombosis or a thromboembolism

9. Concurrent use of the aromatase inhibitor exemestane, as it is structurally similar to
an androgen

10. Concurrent radiation therapy or chemotherapy

11. Current or planned use of cyclosporine, anticoagulants, oxphenbutazone, insulin, oral
or injectable vitamin D doses over 4,000IU/day, or tamoxifen