Opera® for Aromatase Inhibitor-related Arthralgia Management (AIA)

Study Overview
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Brief Summary
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In this phase II, multicenter, self-controlled clinical trial, we will evaluate the safety and efficacy of OPERA® for treating anti-aromate inhibitors (AIs) induced arthralgia. The diagnosis of arthralgia will be based on the NCI-CTCAE v4.0 grade of ≥ 1 , A disorder characterized by a sensation of marked discomfort in a joint, mild pain (grade 1). Arthralgia will be assessed at the enrollment and every two months until the sixth month.

Detailed Description
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Aromatase Inhibitors (AIs) are recommended for the adjuvant treatment of hormone receptor positive breast cancers in the post-menopausal population. Compared with Tamoxifen, third generation aromatase inhibitors have been shown to significantly improve disease free survival (DFS), and include the steroidal inhibitor exemestane, and the nonsteroidal inhibitors, anastrozole and letrozole. Although the AIs are associated with fewer thromboembolic events and endometrial abnormalities than is tamoxifen, approximately 25% of postmenopausal women on AI report arthralgia, skeletal, and muscle pain. The multicentre double-blind placebo-controlled ma.17 trial by the National Cancer Institute of Canada Clinical Trials Group revealed marked increases in arthralgia (25% vs. 21%) and myalgia (15% vs. 12%) in patients on letrozole as compared with those on placebo. The Intergroup Exemestane Study shown a link between arthralgia and the ai exemestane (5.4% exemestane vs. 3.6% tamoxifen).The Arimidex, Tamoxifen Alone or in Combination (atac) trial, after 68 months' median follow-up, showed that the incidence of arthralgia was significantly higher in the anastrozole group than in the tamoxifen group [1100 of 3092 (35.6%) vs. 911 of 3094 (29.4%) patients]. Currently, evidences of drugs efficacy to reduce these side effects are sparse.OPERA® (GAMFARMA srl, Milan, Italy) is a new dietary supplement where α-Lipoic acid (240mg), BS (40mg), MSM (200mg) and Bromelain (20mg) are combined together in a single hard-gelatin capsule. The aim of this prospective study is to determine the efficacy and safety of OPERA® supplementation in a series of patients affected by arthralgia during AI treatment.

Official Title
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Use of an Alfa-lipoic, Methylsulfonylmethane and Bromelain Dietary Supplement (Opera®) for Aromatase Inhibitor-related Arthralgia Management (AIA)

Conditions
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Breast Cancer, Hormone Receptor Positive Tumor, Arthralgia

Intervention / Treatment
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* Dietary Supplement: OPERA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older Karnofsky performance score≥70 Indication for AI treatment in adjuvant setting for breast cancer Arthralgia with grade ≥0-1 Exclusion Criteria: Concomitant diseases, e.g. diabetes, renal insufficiency, alcohol abuse Concomitant rheumatological disease (Rheumatoid arthritis, Spondyloarthropathies, Psoriatic arthritis, etc.) Concomitant endocrinological disease (Acromegaly , Emocromatosis, etc) Any conditions that would complicate arthralgia assessment (e.g. Trauma, Glucocorticoid withdrawal, Hypertrophic osteoarthropathy, Osteoarthritis, Avascular necrosis, Gout, Systemic lupus erythematosus, Septic arthritis, etc.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPERA<br>Women receiving adjuvant aromates-inhibitor with arhtralgia grade ≥ 1 (CTACAE 4.03) | Dietary Supplement: OPERA<br>* All patients were required to take an OPERA® capsule (dietary supplement where α-lipoic acid, Boswellia Serrata, methylsulfonylmethane and bromelain are combined in a single capsule) once daily,from enrollment up to sixth months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of AI induced arthralgia at 6 months | Reduction of AI-induced arthralgia assessed with VAS scale (0, no pain, to 5, worst pain) | 6 months | 
| Reduction of AI induced arthralgia at 6 months | Reduction of AI-induced arthralgia assessed with PRAI questionnaire (16 items that query pain severity over the last 7 days in eight joints using a rating scale of 0-10, with 10 being greatest severity) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QoL | Quality of life assessed with FACT-ES questionnaire (19 items which assess endocrine complaints and adverse effects with response scores ranging from 0 to 4 ('not at all', 'a little bit', 'somewhat', 'quite a bit', and 'very much.') | 6 months | 
| Compliance | Compliance to AI therapy (percentage of patients that have not discontinued and/or changed originally prescribed anti-aromatase inhibitor) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, luminal tumor, anti-aromatase inhibitors, arthralgia, dietary supplement