Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Placebo-Controlled Phase III Study of Duloxetine for Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in Women With Early Stage Breast Cancer
Brief Summary: RATIONALE: Duloxetine hydrochloride may lessen muscle, bone, and joint pain caused by hormone therapy. It is not yet known whether duloxetine hydrochloride is more effective than a placebo in treating patients with muscle, bone, and joint pain caused by hormone therapy.

PURPOSE: This randomized phase III trial studies how well duloxetine hydrochloride works compared to a placebo in treating muscle, bone, and joint pain in patients with early-stage breast cancer receiving hormone therapy.


Options:
A: Inclusion Criteria:

* Age \>18 years
* Diagnosis of gynecologic (ovarian; cervical; uterine; primary peritoneal), lung (non-small cell; small cell), gastrointestinal (colorectal, rectal, gastric, esophageal, GI neuroendocrine, small intestine malignancy, pancreatic, hepatocellular), breast, bladder cancer or prostate malignancy
* Receiving primary medical oncology care at MSKCC medical oncology outpatient clinics
* Receiving cytotoxic chemotherapy not on a clinical trial (or a new hormonal therapy in the case of prostate cancer patients only), with treatment expected to continue for at least four weeks from the time of enrollment
* Signed informed consent and Research Authorization

Exclusion Criteria:

* ECOG performance status greater than 2
* Unable to read and comprehend English language text
B: DISEASE CHARACTERISTICS:

* Histologically confirmed resectable adenocarcinoma of the breast

  * pT1, pT2, pT3, or minimal dermal involvement on pathology only
  * pN0, pN1, pN2, or M0

    * Negative nodal status

      * At least 8 nodes are negative
    * Unknown nodal status

      * Less than 8 nodes examined and no pathological finding
    * Positive nodal status

      * Any positive finding independent of the number of nodes examined
  * Negative sentinel node or no prior nodal dissection allowed if all other criteria met
* Must have had total mastectomy, lumpectomy, or quadrantectomy

  * Should have prior chest wall radiotherapy after segmental mastectomy or histopathologic T4 dermal involvement
* Stage I, II, or IIIa allowed if the tumor is completely removed macroscopically and margins of the resected tumor are microscopically free of tumor
* Must undergo chest wall radiotherapy or second resection if microscopic disease at the mastectomy margins
* No bilateral disease except in situ disease, either ductal or lobular of the contralateral breast
* Postmenopausal

  * Regardless of prior hormonal replacement therapy (HRT) or hysterectomy:

    * Bilateral oophorectomy and any age
    * Radiologic castration and amenorrheic for at least 3 months and any age
    * Not postmenopausal at the start of adjuvant chemotherapy AND and completed at least 6 courses of prior cyclophosphamide, methotrexate, and fluorouracil (CMF) or at least 4 courses of prior anthracycline-cyclophosphamide continuation therapy and at least age 45 with follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) postmenopausal levels
  * No prior HRT:

    * Prior hysterectomy and less than age 55 with FSH/LH/E2 postmenopausal levels
    * Prior hysterectomy and at least age 55
  * No prior HRT or hysterectomy:

    * Amenorrhea more than 1 year and less than age 50
    * Amenorrhea more than 6 months and at least age 50
  * Prior HRT regardless of hysterectomy:

    * At least 1 month since prior HRT and less than age 55 with FSH/LH/E2 postmenopausal levels
    * At least 1 month since prior HRT and at least age 55
  * FSH/LH/E2 postmenopausal levels and uncategorized
* No distant metastases, including bone scans showing hot spots unconfirmed as benign disease or skeletal pain of unknown cause
* At least 10% hormone receptor-positive tumor cells
* Hormone receptor status:

  * Estrogen receptor positive AND/OR
  * Progesterone receptor positive

PATIENT CHARACTERISTICS:

Age:

* 30 and over

Sex:

* Female

Menopausal status:

* Postmenopausal

Performance status:

* Not specified

Life expectancy:

* Not specified

Hematopoietic:

* WBC greater than 3,000/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin greater than 10 g/dL

Hepatic:

* Bilirubin less than 3.0 mg/dL
* SGOT or SGPT less than 1.5 times upper limit of normal
* No hepatic disease that would preclude study

Renal:

* Creatinine less than 1.8 mg/dL
* No renal disease that would preclude study

Cardiovascular:

* No cardiovascular disease that would preclude study
* Prior deep vein thrombosis allowed if medically stable

Pulmonary:

* No lung embolism

Other:

* No other prior or concurrent malignancy within the past 5 years except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
* No prior noncompliance to medical regimens
* No other nonmalignant systemic diseases that would preclude follow-up
* HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Prior immunotherapy or biological response modifiers (e.g., interferon) allowed

Chemotherapy:

* See Disease Characteristics
* Prior adjuvant or neoadjuvant chemotherapy allowed
* Concurrent adjuvant chemotherapy allowed

Endocrine therapy:

* See Disease Characteristics
* Prior neoadjuvant hormonal therapy allowed (e.g., antiestrogens, progestins, or aromatase inhibitors) if no more than 4 months duration and no disease progression
* Prior corticosteroids allowed
* At least 4 weeks since prior HRT
* Prior adjuvant antiestrogen therapy allowed if less than 1 month duration and immediately after surgery, radiotherapy, and/or chemotherapy
* Prior antiestrogens for chemoprevention allowed if at least 18 months between completion of chemoprevention and diagnosis
* No other concurrent antiestrogens or aromatase inhibitors
* No concurrent raloxifene
* No concurrent systemic HRT with or without progestins of more than 3 months duration

Radiotherapy:

* See Disease Characteristics
* Concurrent radiotherapy allowed

Surgery:

* See Disease Characteristics

Other:

* At least 30 days since prior systemic investigational drugs
* At least 7 days since prior topical investigational drugs
* Concurrent bisphosphonates allowed
C: Inclusion Criteria:

* Postmenopausal status
* Currently being treated with an AI in the adjuvant setting (minimum for 8 weeks)
* AIMSS as determined by new or worsened musculoskeletal complaints following AI therapy
* Vitamin D deficiency (\<30ng/ml)
* Caucasian

Exclusion Criteria:

* Hormone replacement therapy last 6 months
* Current use or in the last 12 months of bisphosphonates
* Tamoxifen use in last 6 months
* History of kidney stones
* History of hypercalcemia/hypercalciuria or hyperthyroidism
* Paget's disease of the bone
* Current use of Digitalis/digoxin or thiazide diuretics
* Current use of vitamin D (or multivitamin) supplementation should be stopped
D: DISEASE CHARACTERISTICS:

* Patients must be women with histologically confirmed estrogen receptor (ER)- and/or progesterone receptor (PgR)-positive invasive carcinoma of the breast with no evidence of metastatic disease (M0)
* Patients must have completed mastectomy or breast-sparing surgery and must have recovered from all side effects of the surgery
* Patients must have aromatase inhibitor (AI)-associated musculoskeletal symptoms that began or increased after starting AI therapy; new musculoskeletal pain must not be due specifically to fracture or traumatic injury
* Patients must have completed the S1202 Brief Pain Inventory-Short Form (BPI-SF) within 7 days prior to registration; patients must have an "average pain" of at least 4 on the BPI-SF

PATIENT CHARACTERISTICS:

* Patients must be post-menopausal, as defined by at least one of the following:

  * At least 12 months since the last menstrual period
  * Prior bilateral oophorectomy
  * Previous hysterectomy with one or both ovaries left in place (or previous hysterectomy in which documentation of bilateral oophorectomy is unavailable) AND follicle-stimulating hormone (FSH) values consistent with the institutional normal values for the post menopausal state; if patient is under the age of 55, FSH levels must be obtained within 28 days prior to registration OR
  * Have been on LHRH agonist therapy for at least 3 months and estradiol levels drawn within 28 days prior to registration are consistent with the institutional normal values for post-menopausal state.
* Patients must have Zubrod performance status of 0-2
* Patients must have no known allergy or hypersensitivity to duloxetine or any of the inactive ingredients in the matching placebo
* Patients must not have any contraindicated concurrent illnesses listed on the duloxetine package insert including:

  * Current primary psychiatric diagnosis (schizophrenia, psychosis) or suicidal ideation, history of bipolar disorder, or seizure disorder
  * History of alcohol or other substance abuse or dependence within 365 days prior to registration
  * Chronic liver disease
  * End-stage renal disease
  * Uncontrolled narrow-angle glaucoma
  * Clinically significant coagulation disorder
* Creatinine clearance \> 30 mL/min
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both within 3 x upper limit of normal
* Total bilirubin within the upper limit of normal
* Patients must be able to complete study questionnaires in English or Spanish
* Patients must not have concurrent medical/arthritic disease that could confound or interfere with evaluation of pain or efficacy including: inflammatory arthritis (rheumatoid arthritis, systemic lupus, spondyloarthropathy, psoriatic arthritis, polymyalgia rheumatica), or cancer involving the bone
* Patients must be willing to submit blood samples for correlative studies; baseline samples must be obtained prior to beginning protocol treatment

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* If patients were treated with chemotherapy and/or radiation therapy, these treatments must be completed at least 28 days prior to study registration
* Concurrent bisphosphonate and trastuzumab therapies are allowed
* Patients should have recovered from all Grade 2 or higher side effects of chemotherapy and/or radiation therapy with the exception of alopecia and peripheral neuropathy
* Patients must currently be taking one of the following aromatase inhibitor (AI) doses for at least 21 days, but no longer than 12 months, prior to registration and plans to continue for at least an additional 180 days after registration

  * Anastrozole (Arimidex®) 1 mg daily
  * Letrozole (Femara®) 2.5 mg daily
  * Exemestane (Aromasin®) 25 mg daily
* Patients must not be taking any contraindicated medications listed on the duloxetine package insert including the following: treatment with phenothiazines, propafenone, flecainide, or linezolid; treatment with monoamine oxidase (MAO)-inhibitor within 14 days prior to registration; or current use of anticoagulation medication (e.g., heparin, warfarin)
* Patients must not require selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephirine reuptake inhibitors (SNRIs), or tricyclic antidepressants during study participation; patients must have been able to taper and discontinue treatment with these medications at least 7 days prior to registration; patients must not have taken duloxetine or milnacipran within 90 days prior to registration
* Patients who are receiving treatment with narcotics, tramadol, gabapentin, and/or pregabalin must have been taking a stable dose for at least 30 days prior to registration

Answer: D