Clinical trial NCT03384095: Trial of Oral Hyaluronic Acid for the Prevention of Aromatase Inhibitor-Associated Arthralgias
Official title: Single Center, Placebo-Controlled Trial of Oral High-Molecular Weight Hyaluronic Acid for the Prevention of Aromatase Inhibitor-Associated Arthralgias
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Breast Neoplasm Female
Arthralgia
Keywords: Aromatase Inhibitors
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: Indiana University
name: NOW Foods
First posted: 2017-12-27
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This is a single center, double-blinded, placebo-controlled, randomized Phase II trial to determine whether oral hyaluronic acid will prevent aromatase inhibitor (AI)-associated arthralgias. Subjects must have ER/PR-positive breast cancer tumor with history of aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) which resolved after cessation of their AI (anastrazole or letrozole) within 90 days of enrollment. Subjects will be stratified by initial AI, thus within each initial AI, subjects will be randomized to receive either the experimental treatment (hyaluronic acid) or placebo. Subjects will begin the assigned treatment for 2 weeks prior to transitioning to the second AI. Evaluations will be taken at baseline, 6 weeks (1 month on study drug and AI), 14 weeks (3 months on study drug and AI), and at 26 weeks (6 months on study drug and AI). Treatment with hyaluronic acid and placebo will last for 26 weeks total.

Detailed description: Primary Objective To determine whether oral HA will prevent AI-induced arthralgias and preserve physical function.

Secondary Objectives

1. To explore whether oral HA will have an acceptable safety and tolerability profile.
2. To determine whether oral HA will prevent other AI associated symptoms as assessed by patient reported outcomes (PRO's).
3. To assess how many of the subjects are 90% compliant with taking the HA as directed.

Exploratory Objective To determine if mi486, (a microRNA enriched in skeletal muscle) and other biomarkers associated with AIMSS (TNF, IL-6, IL-17) vary with the administration of HA.

Eligibility criteria: Study Population ER/PR-Positive Breast Cancer Subjects whose AIMSS resolved with cessation of their AI and are candidates for switching to a different AI and who meet the inclusion and exclusion criteria will be eligible for participation in this study.

Inclusion Criteria

1. Age ≥ 18 years old.
2. Had been taking anastrazole or letrozole, and discontinued it within the past 90 days due to pain and/or stiffness. The AI-related pain/stiffness must have resolved.
3. Prior tamoxifen use is allowed.
4. A prior switch from exemestane is allowed.
5. Women who have undergone a total mastectomy or breast conserving surgery for Stage 0-3 breast cancer +/- chemotherapy, +/- antiHer2Neu therapy, +/- radiotherapy.
6. Must have ER and/or PR positive tumors.
7. Women who are postmenopausal by the presence of natural amenorrhea ≥ 12 months or by ovarian ablation (bilateral oophorectomy, radiation, or administration of a gonadotropin-releasing hormone agonist).
8. Eastern Cooperative Oncology Group Performance Score (ECOG PS) 0-3 (Appendix II).
9. Patients may or may not be taking non-opioid analgesics.
10. Adequate renal and hepatic function:

    i) Include only subjects with AST and ALT \< 2.0 × ULN; AP \< 1.5 × ULN; total bilirubin \< 1.2 × ULN ii) Include only subjects with as calculated creatinine clearance (CrCl) \> 60 mL/min determined by the central laboratory using the modified Cockcroft-Gault equation; blood urea nitrogen (BUN) \< 1.5 × upper limit of normal (ULN)
11. Written informed consent from subject and ability for subject to comply with the requirements of the study.

Exclusion Criteria

1. Presence of residual or recurrent cancer.
2. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
3. Consumption of HA-containing supplements in the four weeks prior to study.
4. Known allergy to microcrystalline cellulose or HA. Any questionable reaction to injected HA will be thoroughly investigated.
5. Prolonged systemic corticosteroid treatment, except for topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airway diseases), eye drops or local insertion (i.e., intra-articular). A short duration of systemic corticosteroids is allowed but not within 30 days prior to registration.
6. Self-reported compliance issues and lack of regular prescription filling.
7. Previous diagnosis of fibromyalgia and/or rheumatoid arthritis.

Primary outcomes:
measure: Difference in mean change in joint pain between HA and placebo groups
timeFrame: 14 weeks
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events (i.e. safety and tolerability of HA)
timeFrame: 30 weeks
measure: Difference in mean joint symptoms between HA and placebo groups
timeFrame: 6, 14, and 26 weeks
measure: Difference in mean joint function between HA and placebo groups
timeFrame: 6, 14, and 26 weeks
measure: Difference in mean quality of sleep between HA and placebo groups
timeFrame: 6, 14, and 26 weeks
measure: Difference in global change between HA and placebo groups
timeFrame: 6, 14, and 26 weeks
measure: Difference in mean change in WOMAC subscale 1 scores between HA and placebo groups
timeFrame: 6, 14, and 26 weeks
measure: Difference in mean change in WOMAC subscale 2 scores between HA and placebo groups
timeFrame: 6, 14, and 26 weeks
measure: Difference in mean change in WOMAC subscale 3 scores between HA and placebo groups
timeFrame: 6, 14, and 26 weeks
measure: Time to discontinuation of second aromatase inhibitor due to AIMSS between HA and placebo groups
timeFrame: 26 weeks
measure: Proportion of patients that remain on second aromatase inhibitor between HA and placebo groups
timeFrame: 26 weeks
measure: Rate of 90% compliance between HA and placebo groups
timeFrame: 26 weeks
measure: Mean frequency of as needed analgesia between HA and placebo groups
timeFrame: 6, 14, and 26 weeks
Other outcomes:
Locations:
city: Carmel
country: United States
facility: Indiana University Health North Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Health Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Health Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Spring Mill Medical Center
state: Indiana
Study officials:
affiliation: Indiana University
name: Erin Newton, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roberts KE, Adsett IT, Rickett K, Conroy SM, Chatfield MD, Woodward NE. Systemic therapies for preventing or treating aromatase inhibitor-induced musculoskeletal symptoms in early breast cancer. Cochrane Database Syst Rev. 2022 Jan 10;1(1):CD013167. doi: 10.1002/14651858.CD013167.pub2.