A Phase II Single-Arm Pilot Study of Hydroxychloroquine for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- To evaluate the efficacy of hydroxychloroquine
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years at the time of informed consent
- •Ability to provide written informed consent and HIPAA authorization
- •Diagnosis of DCIS or stage I, II, or III breast cancer
- •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
- •New or worsening self-reported musculoskeletal pain that began or significantly worsened after initiation of AI therapy
- •BPI average pain score of ≥ 4 during screening
- •ECOG PS 0-2
- •Adequate organ function:
- •Absolute neutrophil count ≥1,500/µL
- •Hemoglobin ≥11.0 g/dL
- •Platelet count ≥100,000/µL
- •Serum creatinine ≤1.5× upper limit of normal (ULN) or eGFR ≥60 mL/min/1.73m2
- •Total bilirubin ≤1.5× ULN (except in patients with documented Gilbert's disease, who must have a total bilirubin < 3.0 mg/dL)
- •AST and ALT ≤1.5× ULN
- •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
排除标准
- •Current or prior use of hydroxychloroquine or chloroquine within 6 months
- •Known hypersensitivity to hydroxychloroquine, chloroquine, or 4-aminoquinoline compounds
- •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)
- •History of congestive heart failure (any NYHA class)
- •QTc prolongation (>450 msec) at screening or history of significant arrhythmias requiring treatment
- •Moderate to severe renal impairment (eGFR <60 mL/min/1.73m2)
- •Use of a prohibited concomitant medication (refer to Section 6.3.2) that cannot be discontinued or changed to an alternate therapy
- •Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
- •History of porphyria
- •History of psoriasis
- •History of antiepileptic medications
- •Known history of inflammatory arthritis (example: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis) or connective tissue disease (example: systemic lupus erythematosus, scleroderma, polymyositis)
- •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
- •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
- •Other active malignancy other than breast cancer requiring systemic therapy
- •Pregnant or lactating
- •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
- •Significant psychiatric illness, in the opinion of the investigator, that would limit compliance with study requirements
- •Any active suicidality or history of active suicidal ideation/behavior/attempt within 1 year prior to screening
- •Any other condition that, in the opinion of the investigator, would make the patient unsuitable for study participation
研究组 & 干预措施
Hydroxychloroquine sulfate
Hydroxychloroquine sulfate, 400 mg orally once daily
干预措施: Hydroxychloroquine Sulfate (HCQ) (Drug)
结局指标
主要结局
To evaluate the efficacy of hydroxychloroquine
时间窗: 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).
次要结局
- Patient-reported global impression of change(Week 12)
- Proportion of patients achieving a clinically meaningful improvement(Day 1 and Week 12)
- Changes in BPI Worst Pain and Pain Interference scores(Day 1 and Week 12)
- Changes in endocrine therapy related quality of life(Day 1 and Week 12)
- Changes in grip strength(Day 1 and Week 12)
- Safety of hydroxychloroquine in this patient population(Day 1, Week 4, Week 12, 30 days post EOT)
- Tolerability of hydroxychloroquine in this patient population(Day 1, Week 4, Week 12, 30 days post EOT)
- Adherence to aromatase inhibitor therapy(Screening, Day 1, and Week 12)
研究者
Tarah J Ballinger, MD
Associate Professor
Indiana University