Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 2 Study Vitamin D3 Effects on Musculoskeletal Symptoms With Use of Aromatase Inhibitors
Brief Summary: The Purpose of this study is to determine whether vitamin D3 supplements will decrease the muscle and bone pain that are reported by women who take Aromatase Inhibitors.


Options:
A: Inclusion Criteria:

* Age ≥ 18 years
* Women with a history of stage I-IIIa invasive breast cancer
* History of hormone-receptor positive cancer (either ER + or PR + or both)
* Are prescribed and are taking anastrozole, letrozole or exemestane for at least one month and have at least 7 months of AI treatment remaining
* Are experiencing AIMSS

Exclusion Criteria:

* Unable to read or understand English
* History of psychiatric disability affecting informed consent or compliance with drug intake
* Malabsorption syndrome or inability to take oral medication
* Has less than 7 months of AI therapy remaining
B: 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
C: 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.
D: DISEASE CHARACTERISTICS:

* Histologically confirmed primary invasive adenocarcinoma of the breast

  * Stage I, II, or IIIA disease
  * No metastatic disease
* Must have undergone modified radical mastectomy or breast-sparing surgery and recovered
* Estrogen-receptor positive (ER+) and/or progesterone-receptor positive (PR+)
* Currently taking a third-generation aromatase inhibitor (AI) \[e.g., anastrozole (Arimidex®), letrozole (Femara®), or exemestane (Aromasin®)\] for ≥ 90 days prior to registration with plans to continue for ≥ 180 days after registration
* Must have completed the S092 Brief Pain Inventory (BPI)-Short Form within the past 14 days, and must have a worst pain/stiffness of ≥ 5 on the BPI (item #2) that has started or increased with AI therapy

PATIENT CHARACTERISTICS:

* Postmenopausal
* Zubrod performance status 0-2
* Willing to submit blood for serum-free estradiol, total estradiol, serum inflammatory markers (IL6, TNF-α, CRP), DHA and EPA, lipid profile (LDL, HDL, triglycerides), and DNA analysis (CYP19A1)
* Able to complete study questionnaires in English
* At least 5 years since other malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, ductal carcinoma in situ of the breast or adequately treated stage I or II cancer from which the patient is currently in complete remission
* Patients must not have a known allergy to soy, given that the placebo is suspended in soybean oil

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 3 months since prior omega-3 fatty acid supplements and must agree to refrain from omega-3-fatty acid supplements from sources outside of this study
* More than 28 days since prior investigational agents
* No other medical therapy, alternative therapy, or physical therapy for joint pain/stiffness within the past 30 days
* Patients must not be on anticoagulation medication (i.e., heparin/warfarin) because of increased risk of bleeding within 28 days prior to registration
* Patients must not have a history of bone fracture or surgery of the afflicted knees and/or hands within 6 months prior to registration
* Patients must not be on narcotics within 14 days of registration
* Patients may have received corticosteroid treatment; however, the following criteria apply:

  * Patients must not have received oral or intramuscular corticosteroids within the 28 days prior to registration
  * Patients must not have received intra-articular steroids to the study, or any other, joint within 28 days prior to registration
* Patients must not have received topical analgesics (e.g., capsaicin preparations) to the study joint or any other analgesics (e.g., opiates, tramadol; with the exception of nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen) within 14 days prior to registration

Answer: A