Pilot Study of Hydroxychloroquine for the Treatment of AIMSS (AIMSS)

A Phase II Single-Arm Pilot Study of Hydroxychloroquine for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Syndrome

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Joint Pain; Aromatase Inhibitor Associated Musculoskeletal Symptoms (AIMSS)
• Intervention / Treatment: Drug: Hydroxychloroquine Sulfate (HCQ)

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.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Niraj Shah, MS; Phone Number: 317-278-3420; Email: shahnir@iu.edu

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Comprehensive Cancer Center
      • Principal Investigator: Tarah Ballinger, MD
      • Contact: Niraj Shah, MS; Phone Number: 317-278-3420; Email: shahnir@iu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydroxychloroquine sulfate; Hydroxychloroquine sulfate, 400 mg orally once daily	Drug: Hydroxychloroquine Sulfate (HCQ); Drug: Hydroxychloroquine sulfate Dose: 400 mg orally once daily Duration: 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of hydroxychloroquine	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).	Day 1 and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients achieving a clinically meaningful improvement	To assess the proportion of patients achieving a clinically meaningful improvement (≥2-point reduction) in BPI Average Pain score.	Day 1 and Week 12
Changes in BPI Worst Pain and Pain Interference scores	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).	Day 1 and Week 12
Changes in endocrine therapy related quality of life	To assess changes in endocrine therapy related quality of life by FACT-ES (5 point Likert-type scale).	Day 1 and Week 12
Changes in grip strength	To assess changes in grip strength as an objective measure of function using Jamar hand dynamometers (scale of 0-200lbs).	Day 1 and Week 12
Patient-reported global impression of change	To evaluate patient-reported global impression of change using the Patient Global Impression of Change (PGIC) (scale 0-6, 6 being the worst outcome).	Week 12
Safety of hydroxychloroquine in this patient population	To assess safety of hydroxychloroquine in this patient population using NCI CTCAE v5.0 (grade 1-5, 5 being the worst outcome).	Day 1, Week 4, Week 12, 30 days post EOT
Tolerability of hydroxychloroquine in this patient population	To assess tolerability of hydroxychloroquine in this patient population via number of patients who completed treatment.	Day 1, Week 4, Week 12, 30 days post EOT
Adherence to aromatase inhibitor therapy	To evaluate adherence to aromatase inhibitor therapy during the study period via number of patients who completed treatment based on self-report.	Screening, Day 1, and Week 12

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: 100 Voices of Hope
• Investigators: Principal Investigator: Tarah Ballinger, MD, IUSCCC

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: August 25, 2026
• First Submitted That Met QC Criteria: September 16, 2026
• First Posted (Actual): September 17, 2026

Study Record Updates

• Last Update Posted (Actual): September 17, 2026
• Last Update Submitted That Met QC Criteria: September 16, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Hydroxychloroquine; Joint Pain; Aromatase Inhibitor Associated Musculoskeletal Symptoms (AMISS)
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Neoplasms by Site; Neoplasms; Joint Diseases; Skin Diseases; Breast Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Breast Neoplasms; Arthralgia; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinolines; Aminoquinolines; Chloroquine; Hydroxychloroquine
• Other Study ID Numbers: CTO-IUSCCC-0959

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No