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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01573442
Recruitment Status : Completed
First Posted : April 9, 2012
Results First Posted : June 5, 2019
Last Update Posted : October 15, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Brief 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.

Condition or disease Intervention/treatment Phase
Arthralgia Breast Cancer Hot Flashes Musculoskeletal Complications Sexual Dysfunction Drug: testosterone Other: placebo Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 227 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
Official Title: Randomized Double-Blind Placebo Controlled Study of Testosterone in the Adjuvant Treatment of Postmenopausal Women With Aromatase Inhibitor Induced Arthralgias
Actual Study Start Date : August 2013
Actual Primary Completion Date : February 28, 2018
Actual Study Completion Date : September 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm I
Patients receive testosterone (0.264mL) topical application daily for six months.
Drug: testosterone
10.4 mg

Placebo Comparator: Arm II
Patients receive placebo (0.264mL) topical application daily for six months.
Other: placebo



Primary Outcome Measures :
  1. Change in Item #3 (Average) of the Brief Pain Inventory (BPI) Average Pain From Baseline to Month 3 [ Time Frame: From baseline to 3 months ]
    The average change in Brief Pain Inventory (BPI) Average Pain scores between baseline and month 3 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine.

  2. Improvement in BPI Average Pain From Baseline to Month 3 [ Time Frame: Up to 3 months ]
    "2. Was there an improvement in BPI Average Pain from baseline to month 3?"

  3. Change in BPI Average Change From Baseline Pain Score to Month Six Average Pain Score [ Time Frame: Baseline and 6 months ]
    Change in BPI Average Change from Baseline Pain Score to Month Six Average Pain Score. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine.

  4. Change in BPI Average Pain From Baseline to Month 1-6 [ Time Frame: Baseline and months 1-6 ]
    Change in BPI Average Pain from baseline to month 1-6. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine.


Secondary Outcome Measures :
  1. Number of Participants With Grade 3 Or Higher Adverse Events Considered At Least Possibly Related to Treatment [ Time Frame: Up to 6 months ]
    The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.

  2. Number of Patients Who Reported Alopecia Using CTCAE 4.0 [ Time Frame: Up to 6 months ]
    The number of patients who reported alopecia using CTCAE 4.0 is reported below for each arm.

  3. Number of Patients Who Reported Acne Using CTCAE 4.0 [ Time Frame: Up to 6 months ]
    The number of patients who reported acne using CTCAE 4.0 is reported below for each arm.

  4. Number of Patients Who Reported Hirsutism Using CTCAE 4.0 [ Time Frame: Up to 6 months ]
    The number of patients who reported hirsutism using CTCAE 4.0 is reported below for each arm by grade.

  5. Change in Hot Flash Frequency From Baseline to Week 8 [ Time Frame: baseline and week 8 ]
    Change in hot flash frequency from baseline to week 8. Hot flash frequency is a count of the number of hot flashes per day and is a number from 0 to infinity. Higher values are worse.

  6. The Change of Libido From Baseline to Month 3 as Measured by the MENQOL [ Time Frame: baseline and month 3 ]
    Change in how bothered are you by decreased sex drive from baseline to month 3. This is assessed using one question off of the MENQOL (Menopause-Specific Quality of Life) questionnaire. The question asks "How bothered are you by a decrease in your sexual drive". This is collected on a scale ranging from 0=Not at all bothered to 6=Extremely bothered, with higher values being worse.

  7. The Change of Menopause Specific Quality of Life From Baseline to Month 3 as Measured by MENQOL "How Bothered Are You by Hot Flashes" [ Time Frame: baseline and month 3 ]
    The change of menopause specific quality of life from baseline to month 3 as measured by MENQOL "how bothered are you by Hot Flashes". This is one question from the MENQOL (Menopause-Specific Quality of Life) questionnaire. The question asks "How bothered are you by hot flashes or flushes". This is collected on a scale ranging from 0=Not at all bothered t 6=Extremely bothered, with higher values being worse.

  8. Change in BPI Worst Pain From Baseline to Month 3 [ Time Frame: baseline and month 3 ]
    Change in BPI Worst Pain from baseline to month 3. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine.

  9. Change in BPI Least Pain From Baseline to Month 3 [ Time Frame: baseline and month 3 ]
    Change in BPI Least Pain from baseline to month 3. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine.

  10. Change in BPI Pain Right Now From Baseline to Month 3 [ Time Frame: baseline and month 3 ]
    Change in BPI Pain right now from baseline to month 3. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine.

  11. Change in Average Joint Stiffness From Baseline to Month 3 as Measured by BPI Item #5 (Joint Stiffness) [ Time Frame: baseline and month 3 ]
    Change in average joint stiffness from baseline to month 3. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine.

  12. 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: baseline and month 3 ]
    The intrapatient change in activity level (interference of activity) for each month from baseline as measured by item#6 (interference) of the BPI-AIA. Change in general activity from baseline to month 3. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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-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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01573442


  Show 529 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
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Study Chair: Charles Loprinzi, MD Mayo Clinic
  Study Documents (Full-Text)

Documents provided by Alliance for Clinical Trials in Oncology:

Additional Information:
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Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01573442     History of Changes
Other Study ID Numbers: A221102
CDR0000730083 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-2012-00719 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
U10CA037447 ( U.S. NIH Grant/Contract )
UG1CA189823 ( U.S. NIH Grant/Contract )
First Posted: April 9, 2012    Key Record Dates
Results First Posted: June 5, 2019
Last Update Posted: October 15, 2019
Last Verified: October 2019
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:
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Breast Neoplasms
Arthralgia
Hot Flashes
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Signs and Symptoms
Joint Diseases
Musculoskeletal Diseases
Pain
Neurologic Manifestations
Methyltestosterone
Testosterone
Testosterone undecanoate
Testosterone enanthate
Testosterone 17 beta-cypionate
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
Estrogen Antagonists
Hormone Antagonists