Please select the eligibility criteria that correspond to the clinical trial below.
Title: Single Center, Placebo-Controlled Trial of Oral High-Molecular Weight Hyaluronic Acid for the Prevention of Aromatase Inhibitor-Associated Arthralgias
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.


Options:
A: Inclusion Criteria:

* Women diagnosed with breast cancer stages I-III initiating first line adjuvant aromatase inhibitor (AI) therapy with any of the FDA-approved AIs (anastrazole, exemestane, letrozole)
* Concurrent gonadotropin-releasing hormone (GnRH) agonist therapy is allowed; concurrent breast related radiation therapy is allowed.
* Prior tamoxifen use is allowed
* Prior chemotherapy is allowed
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Metastatic malignancy of any kind
* Rheumatoid arthritis and other types of autoimmune and inflammatory joint disease
* AI use \> 21 days prior to study enrollment
* Known bleeding disorders
* Current use of warfarin or other anticoagulants
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
* Daily use of n-3 PUFA concentrates or capsules or any other supplements that might interact with n-3 PUFA supplements if \> 375 mg per day of of eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA) within six months of study initiation
* Pregnant or nursing women
* Known sensitivity or allergy to fish or fish oil
* Unable to give informed consent
B: 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.
C: DISEASE CHARACTERISTICS:

* Diagnosis of cancer

  * CNS malignancy allowed with the exception of leptomeningeal carcinomatosis
* Must have painful sensory chemotherapy-induced peripheral neuropathy (CIPN) resulting from prior treatment with single-agent taxane or platinum agents (paclitaxel, docetaxel, nab-paclitaxel, oxaliplatin, cisplatin) (may not have received drugs from both classes)

  * CIPN \> grade 1 as measured by NCI-CTCAE v 4.0
  * Average neuropathic pain score ≥ 4
* Patients with the following illnesses known to cause peripheral neuropathy are eligible, provided they have no evidence of neuropathy from these illnesses:

  * Diabetes mellitus
  * Peripheral vascular disease
  * HIV infection
  * Significant degenerative or familial neurologic disorder known to cause peripheral neuropathy
* No clinical or subclinical neuropathy from nerve compression injuries (i.e., carpal tunnel syndrome, brachial plexopathy, spinal stenosis, or spinal nerve root compression)

PATIENT CHARACTERISTICS:

* AST ≤ 3 times upper limit of normal
* Total bilirubin ≤ normal
* Creatinine clearance \> 30 mL/min
* Not pregnant or nursing
* Able to take oral or enteral medication
* No history of seizure disorder
* No diagnosis of ethanol addiction or dependence within the past 10 years
* No history of narrow-angle glaucoma
* None of the following:

  * History of suicidal thoughts
  * Symptoms of or history of schizophrenia, bipolar disease, or a major depression
  * Serious eating disorder such as bulimia or anorexia where electrolyte imbalance is likely

PRIOR CONCURRENT THERAPY:

* At least 3 months since prior and no concurrent taxane or platinum agent
* At least 14 days since prior and no concurrent monoamine oxidase inhibitors or other antidepressants
* No other prior or concurrent neurotoxic drugs (e.g., vincristine, vinblastine, cytarabine, thalidomide, bortezomib, carboplatin, or procarbazine)
* No concurrent anticonvulsants
* No concurrent B or E vitamin supplementation in doses greater than the recommended daily allowance (RDA)

  * Centrum (standard formula) and One-A-Day "essential" formula which contain 100% RDA for vitamins B6, E, and B12 allowed
  * Other multivitamins allowed provided they contain no more than 100% RDA of B vitamins and vitamin E
* No concurrent treatment (pharmacologic) for depression
D: DISEASE CHARACTERISTICS:

* Planning to begin aromatase inhibitor (AI) therapy or taken fewer than 10 doses of adjuvant AI therapy
* Hormone-receptor status not specified

PATIENT CHARACTERISTICS:

* Postmenopausal
* ECOG performance status 0-1
* Able to understand and respond to questions in English
* No condition that would impair the ability to provide informed consent
* No other non-breast cancer condition

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No more than 9 prior doses of AI

Answer: B