Testosterone in Treating Postmenopausal Patients With Arthralgia Caused by Adjuvant Aromatase Inhibitor Treatment
Condition: Arthralgia; Breast Cancer; Hot Flashes; Musculoskeletal Complications; Sexual Dysfunction
MeSH terms: Breast Neoplasms; Arthralgia; Hot Flashes
Intervention: testosterone; placebo
Intervention description: 10.4 mg
Intervention MeSH terms: Testosterone
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 227.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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

Summary:

      This randomized phase III trial studies testosterone to see how well it works compared to
      placebo in treating postmenopausal patients with arthralgia (joint pain) caused by
      anastrozole or letrozole. Testosterone may help relieve moderate or severe arthralgia
      associated with the use of aromatase inhibitors, such as anastrozole or letrozole.
    

Eligibility criteria:

        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