Aromatase Inhibitor Associated Musculoskeletal Symptoms (AIMSS), Breast Cancer, Joint Pain
Conditions
Keywords
Hydroxychloroquine, Joint Pain, Aromatase Inhibitor Associated Musculoskeletal Symptoms (AMISS)
Brief summary
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
Aromatase Inhibitor (AI) therapy is highly effective for post-menopausal, estrogen receptor (ER) positive breast cancer, yet the clinical effectiveness of AI therapy is limited by noncompliance and early treatment discontinuation due to musculoskeletal side effects, which include joint pain, joint stiffness, bone pain, muscle weakness, and myalgias. Methods to improve compliance to AI therapy have the potential to increase survival. This study will look at hydroxychloroquine (HCQ), a disease-modifying antirheumatic drug (DMARD) with well-established anti-inflammatory and immunomodulatory properties. It is FDA-approved for the treatment of conditions characterized by chronic inflammatory joint pain similar to AIMSS. This single-arm, proof of concept study will look for an improvement in joint pain for patients undergoing standard of care treatment involving AI therapy.
Interventions
Drug: Hydroxychloroquine sulfate Dose: 400 mg orally once daily Duration: 12 weeks
Sponsors
Indiana University
100 Voices of Hope
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. Absolute neutrophil count ≥1,500/µL 2. Hemoglobin ≥11.0 g/dL 3. Platelet count ≥100,000/µL 4. Serum creatinine ≤1.5× upper limit of normal (ULN) or eGFR ≥60 mL/min/1.73m2 5. Total bilirubin ≤1.5× ULN (except in patients with documented Gilbert's disease, who must have a total bilirubin \< 3.0 mg/dL) 6. 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 \<60 mL/min/1.73m2) 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the efficacy of hydroxychloroquine | Day 1 and Week 12 | 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 (scored from 0-10; a minimally important difference is a 2-point reduction or 30% from baseline). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients achieving a clinically meaningful improvement | Day 1 and Week 12 | To assess the proportion of patients achieving a clinically meaningful improvement (≥2-point reduction) in BPI Average Pain score. |
| Changes in BPI Worst Pain and Pain Interference scores | Day 1 and Week 12 | To evaluate changes in BPI Worst Pain and Pain Interference scores (scored from 0-10; a minimally important difference is a 2-point reduction or 30% from baseline). |
| Changes in endocrine therapy related quality of life | Day 1 and Week 12 | To assess changes in endocrine therapy related quality of life by FACT-ES (5 point Likert-type scale). |
| Changes in grip strength | Day 1 and Week 12 | To assess changes in grip strength as an objective measure of function using Jamar hand dynamometers (scale of 0-200lbs). |
| Patient-reported global impression of change | Week 12 | To evaluate patient-reported global impression of change using the Patient Global Impression of Change (PGIC) (scale 0-6, 6 being the worst outcome). |
| Safety of hydroxychloroquine in this patient population | Day 1, Week 4, Week 12, 30 days post EOT | To assess safety of hydroxychloroquine in this patient population using NCI CTCAE v5.0 (grade 1-5, 5 being the worst outcome). |
| Tolerability of hydroxychloroquine in this patient population | Day 1, Week 4, Week 12, 30 days post EOT | To assess tolerability of hydroxychloroquine in this patient population via number of patients who completed treatment. |
| Adherence to aromatase inhibitor therapy | Screening, Day 1, and Week 12 | To evaluate adherence to aromatase inhibitor therapy during the study period via number of patients who completed treatment based on self-report. |
Countries
United States
Contacts
CONTACTNiraj Shah, MS
PRINCIPAL_INVESTIGATORTarah Ballinger, MD
IUSCCC
Outcome results
None listed