A Phase Ii Single-Arm Pilot Study of Hydroxychloroquine for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Syndrome (Aimss)
Study of Investigational Medication for Joint Pain in Breast Cancer Patients
Tarah Ballinger, MD
Primary Investigator
Brief description of study
The purpose of this study is to evaluate the effectiveness of hydroxychloroquine sulfate (a type of drug commonly used to treat joint pain caused by inflammation, swelling) in reducing joint pain associated with Aromatase Inhibitor Associated Musculoskeletal Syndrome (AIMSS) for patients with breast cancer.
Detailed description of study
Primary: To evaluate the efficacy of hydroxychloroquine 400 mg daily in reducing joint pain associated with AIMSS as measured by change in Brief Pain Inventory (BPI) Average Pain score from Day 1 to week 12.
Secondary - To assess the proportion of patients achieving a clinically meaningful improvement (>=2-point reduction) in BPI Average Pain score at week 12. - To evaluate changes in BPI Worst Pain and Pain Interference scores from Day 1 to week 12. - To assess changes in endocrine therapy related quality of life by FACT-ES from Day 1 to week 12. - To assess changes in grip strength as an objective measure of function. - To evaluate patient-reported global impression of change using the Patient Global Impression of Change (PGIC) at week 12. - To assess safety and tolerability of hydroxychloroquine in this patient population using NCI CTCAE v.50 and treatment discontinuation rate from Day 1 to 12 weeks. - To evaluate adherence to aromatase inhibitor therapy during the study period based on self-report.Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Aromatase Inhibitor Associated Musculoskeletal Syndrome (AIMSS), Breast Cancer
-
Age: 18 years - 100 years
-
Gender: All
Inclusion Criteria
1. Age ≥ 18 years at the time of informed consent
2. Ability to provide written informed consent and HIPAA authorization
3. Diagnosis of DCIS or stage I, II, or III breast cancer
4. Currently receiving adjuvant aromatase inhibitor therapy (anastrozole, letrozole or
exemestane) for ≥ 4 weeks prior to enrollment
Note: Concurrent use of ovarian suppression is allowed
Note: Concurrent use of CDK4/6 inhibitors is not allowed due to cytopenia risk
5. New or worsening self-reported musculoskeletal pain that began or significantly
worsened after initiation of AI therapy
6. BPI average pain score of ≥ 4 during screening
7. ECOG PS 0-2
8. Adequate organ function:
(a) Absolute neutrophil count ≥1,500/μL
(b) Hemoglobin ≥11.0 g/dL
(c) Platelet count ≥100,000/μL
(d) Serum creatinine ≤1.5× upper limit of normal (ULN) or eGFR ≥60
mL/min/1.73m2
(e) Total bilirubin ≤1.5× ULN (except in patients with documented Gilbert’s
disease, who must have a total bilirubin (f) AST and ALT ≤1.5× ULN
9. Must agree to maintain stable doses of any analgesic medications or other AIMSS
related therapies during the study period
Note: rescue doses of acetaminophen or ibuprofen allowed on a non-daily basis,
unless not new
Exclusion Criteria
1. Current or prior use of hydroxychloroquine or chloroquine within 6 months
2. Known hypersensitivity to hydroxychloroquine, chloroquine, or 4-aminoquinoline
compounds
3. History of retinopathy or retinal vein occlusion issues
Note: While there is an association between retinopathy and HCQ use, this occurs
rarely and with long term use with higher cumulative doses that used here. Other clinical
trials have not required retinal exam (example: CTO-TBCRC04627, approved by IU IRB)
4. History of congestive heart failure (any NYHA class)
5. QTc prolongation (>450 msec) at screening or history of significant arrhythmias
requiring treatment
6. Moderate to severe renal impairment (eGFR 7. Use of a prohibited concomitant medication (refer to Section 6.3.2) that cannot be
discontinued or changed to an alternate therapy
8. Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
9. History of porphyria
10. History of psoriasis
11. History of antiepileptic medications
12. Known history of inflammatory arthritis (example: rheumatoid arthritis, psoriatic
arthritis, ankylosing spondylitis) or connective tissue disease (example: systemic lupus
erythematosus, scleroderma, polymyositis)
13. Recent initiation or dose change (within 4 weeks) of medications for pain management
(NSAIDs, duloxetine, gabapentin, pregabalin, opioids)
Note: Patients on stable doses for >4 weeks are eligible
14. Patients currently receiving or planned to receive high dose systemic treatment with
corticosteroids defined as: cortisone >50mg; hydrocortisone >40mg, prednisone
>10mg, methylprednisolone >8mg or dexamethasone >1.5mg; or another
immunosuppressive agent
Note: Topical or inhaled corticosteroids are allowed
15. Other active malignancy other than breast cancer requiring systemic therapy
16. Pregnant or lactating
17. Co-enrollment in another clinical trial
Note: Patients may co-enroll in other clinical trial(s) if the trial(s) does not interfere with
the objectives of this trial
18. Significant psychiatric illness, in the opinion of the investigator, that would limit
compliance with study requirements
19. Any active suicidality or history of active suicidal ideation/behavior/attempt within 1
year prior to screening
20. Any other condition that, in the opinion of the investigator, would make the patient
unsuitable for study participation
This study investigates the use of an investigational medication to reduce joint pain caused by Aromatase Inhibitor Associated Musculoskeletal Syndrome (AIMSS) in patients with breast cancer. Aromatase inhibitors are drugs used in the treatment of breast cancer, and sometimes they can cause joint pain as a side effect. The purpose of this study is to assess how well the investigational medication works in lowering this joint pain.
Participants in the study will take the investigational medication daily and their joint pain will be measured using a scale called the Brief Pain Inventory. The study will also look at other factors like changes in quality of life, grip strength, and overall impression of change, as reported by the participants. Safety and tolerability of the medication will also be monitored.
- Who can participate: Adults aged 18 and older with a diagnosis of DCIS or stage I-III breast cancer currently receiving aromatase inhibitor therapy may participate. Eligibility includes musculoskeletal pain that started or worsened after starting AI therapy and a pain score of 4 or higher.
- Study details: Participants will take the investigational medication daily and report their pain levels and any changes in quality of life. They must maintain stable doses of other pain medications.
- Study timelines: The study will last 12 weeks.
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