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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01573442
First received: April 6, 2012
Last updated: June 13, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Arthralgia
Breast Cancer
Hot Flashes
Musculoskeletal Complications
Sexual Dysfunction
Drug: testosterone
Other: placebo
Drug: anastrozole
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: Randomized Double-Blind Placebo Controlled Study of Subcutaneous Testosterone in the Adjuvant Treatment of Postmenopausal Women With Aromatase Inhibitor Induced Arthralgias

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Intra-patient change in joint pain at 3 months from baseline as measured by item #3 (average) of the Brief Pain Inventory [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Proportion of women with changes in pain at least 10 points on a converted 0-100 scale at 3 months from baseline [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    Proportion of women with an improvement (reduced pain) of at least 10 points (on a converted 0-100 scale)

  • The intra-patient change in joint pain at 6 months from baseline as measured by item #3 (average) of the Brief Pain Inventory for aromatase inhibitor arthralgias (BPI-AIA). [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • The intra-patient changes in joint pain at each month from baseline as measured by the BPI-AIA. [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of toxicities assessed using the Common Terminology Criteria for Adverse Events (CTCAE) 4.0. [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
  • Alopecia as reported by the patient using CTCAE 4.0 [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
  • Acne as reported by the patient using CTCAE 4.0 [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
  • Hirsutism as reported by the patient using CTCAE 4.0 [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
  • The change of hot flashes during the first two months from baseline as measured by hot flash diary [ Time Frame: Up to 2 months ] [ Designated as safety issue: No ]
  • The change of libido from baseline as measured by POMS monthly. [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • The change of menopause specific quality of life from baseline as measured by MENQOL monthly. [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • The intrapatient change in joint pain for each month from baseline as measured by item#1 (worst) of the BPI-AIA. [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • The intrapatient change in joint pain for each month from baseline as measured by item#2 (least) of the BPI-AIA. [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • The intrapatient change in joint pain for each month from baseline as measured by item#4 (right now) of the BPI-AIA. [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • The intrapatient change in joint pain for each month from baseline as measured by item#5 (stiffness) of the BPI-AIA. [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • The intrapatient change in activity level (interference of activity) for each month from baseline as measured by item#6 (interference) of the BPI-AIA. [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 224
Study Start Date: August 2013
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive testosterone/anastrozole (two pellets) sub Q implant once every 3 months for a total of 2 doses.
Drug: testosterone
120 mg
Drug: anastrozole
8 mg
Placebo Comparator: Arm II
Patients receive placebo (two pellets) sub Q implant once every 3 months for a total of 2 doses.
Other: placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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-opiod 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01573442

Contacts
Contact: Charles Loprinzi, MD (507) 284-4565

  Show 270 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Charles Loprinzi, MD Mayo Clinic
  More Information

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01573442     History of Changes
Other Study ID Numbers: A221102  CDR0000730083  NCI-2012-00719  U10CA037447  UG1CA189823 
Study First Received: April 6, 2012
Last Updated: June 13, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
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

Additional relevant MeSH terms:
Hot Flashes
Breast Neoplasms
Arthralgia
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Signs and Symptoms
Joint Diseases
Musculoskeletal Diseases
Pain
Neurologic Manifestations
Nervous System Diseases
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Anastrozole
Aromatase Inhibitors
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016