Sunitinib Malate and Exemestane in Treating Postmenopausal Women With Breast Cancer

• Status: Unknown status
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: Female

Summary

RATIONALE: Sunitinib malate and exemestane may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving sunitinib malate and exemestane before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of sunitinib malate to see how well it works when given together with exemestane in treating postmenopausal women with breast cancer.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institut Català d'Oncologia
• Treatments: Exemestane; Sunitinib

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast carcinoma meeting the following criteria:

• Estrogen receptor-positive ≥ 50% or Allred score > 6

• HER-2 negative defined as IHC < 2+ and negative FISH/CISH

• Primary tumor measuring ≥ 3 cm if there is no node involvement

• Any T if N1 or N2 disease

• No inflammatory breast cancer (T4d)

• No metastatic disease

• Measurable disease by mammography and/or ultrasound and MRI (if available)

PATIENT CHARACTERISTICS:

• Postmenopausal

• Prior bilateral oophorectomy

• ≥ 60 years of age

• < 60 years of age AND have experienced amenorrhea for ≥ 12 months in the absence of chemotherapy, tamoxifen, or toremifene OR have undergone ovarian suppression and follicle-stimulating hormone and estradiol levels in the postmenopausal range

• ECOG performance status 0-1

• ANC ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 10 g/dL

• Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min

• Bilirubin normal

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)

• Alkaline phosphatase ≤ 2.5 times ULN

• Albumin > 2.5. g/dL

• No known HIV infection

• Adequate left ventricular ejection fraction (LVEF) at baseline defined as LVEF not below normal range by echocardiogram or MUGA

• No evidence of prior uncontrolled hypertension

• Patients with controlled hypertension (systolic < 150 mm Hg and/or diastolic < 90 mm Hg) by antihypertensive therapies allowed

• No prior uncontrolled or symptomatic angina, myocardial infarction, congestive heart failure, clinically significant arrhythmias, or prolongation of the QTc interval

• No hemorrhagic or thrombotic events, including transient ischemic attack, pulmonary embolism, or deep-vein thrombosis, within the past 12 months

• No gross hemorrhage within the past 6 months (e.g., gastrointestinal bleeding, hemoptysis, or hematuria)

• No history or evidence of an inherited bleeding diathesis or coagulopathy at risk of bleeding

• None of the following:

• Unable to swallow oral medications

• Active inflammatory bowel disease

• Partial or complete bowel obstruction

• Chronic diarrhea

• No history of another malignancy within the past 5 years except for cured non-melanoma skin cancer or successfully treated carcinoma in situ of the cervix

• No psychiatric disease or social situations that would limit compliance with study requirements or patient unwilling or unable to comply with protocol for the duration of study

• No unstable or severe intercurrent medical condition that, in the opinion of the investigator, might interfere with the achievement of study objectives

• No known immediate or delayed hypersensitive reaction or idiosyncrasy to drugs chemically related to exemestane or sunitinib malate or their excipients

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior or other concurrent chemotherapy, radiotherapy, immunotherapy, biologic therapy, or hormonal therapy for primary invasive breast cancer

• No concurrent anticoagulant therapy except for low-dose anticoagulants (i.e., low molecular weight heparin or aspirin) for the prevention of deep-vein thrombosis

• No chronic therapy with corticosteroids, except for steroids administered by inhalation

• More than 4 weeks since prior major surgery and ≥ 7 days since prior minor surgery

• No prior or other concurrent investigational anticancer agent

• No concurrent participation in another clinical trial

• No concurrent drugs with potential proarrhythmic activity

• No concurrent known CYP3A4 inhibitors (i.e., grapefruit, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, diltiazem, nefazodone, voriconazole, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, delavirdine)

• No concurrent known CYP3A4 or CYP1A2 inducers (i.e., carbamazepine, dexamethasone, felbamate, omeprazole, efavirenz, tipranavir, phenobarbital, phenytoin, primidone, rifabutin, rifampicin, St. John's wort)