CNF2024 (BIIB021) as Single-Agent Treatment in Subjects With HER2- Advanced Breast Cancer or in Combination With Trastuzumab in Subjects With HER2+ Advanced Breast Cancer This study is closed to enrollment. Purpose The goal of this clinical research study is to study the drug CNF2024 as a single agent or in combination with trastuzumab in patients with advanced breast cancer and to: find the highest dose of the drug CNF2024 as a single agent or in combination with trastuzumab that can be given safely measure levels of CNF2024 as a single agent or in combination with trastuzumab in blood determine if CNF2024 as a single agent or in combination with trastuzumab can stop breast cancer cells from growing Study Design:  Treatment, Non-Randomized, Open Label, Parallel Assignment, Safety Study   Official Title: A Phase 1 Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of CNF2024 as a Single-Agent Treatment in Subjects With HER2- Advanced Breast Cancer or in Combination With Trastuzumab in Subjects With HER2+ Advanced Breast Cancer Further study details as provided by Biogen Idec: Primary Outcome Measures: Clinical and laboratory safety assessments    Estimated Enrollment:   70 Study Start Date:   December 2007 Estimated Study Completion Date:   March 2010 Estimated Primary Completion Date:   September 2009 (Final data collection date for primary outcome measure)   Arms Assigned Interventions A: Experimental Patients with HER2- Breast Cancer Drug: CNF2024 Oral doses of CNF2024 as specified in the protocol. B: Experimental Patients with HER2+ Breast Cancer Drug: CNF2024 + trastuzumab Oral doses of CNF2024 as specified in the protocol Intravenous doses of trastuzumab as specified in the package insert. Eligibility Ages Eligible for Study:   18 Years and older Genders Eligible for Study:   Both Accepts Healthy Volunteers:   No Criteria Inclusion Criteria: Group A: Age ≥18 years at the time of informed consent. Male and female subjects with confirmed HER2 adenocarcinoma of the breast with advanced disease (advanced disease will be defined as metastatic disease or locally advanced disease that is surgically unresectable and considered unmanageable with standard therapies such as radiation or systemic therapies) who have had disease progression on at least one standard hormonal or chemotherapy regimen for advanced breast cancer or who have refused standard therapies. Evaluable disease either by measurable disease (RECIST) or nonmeasurable disease. ECOG ≤2. Required Laboratory Values:ANC ≥1500 cells/mm3,platelet count ≥100,000 cells/mm3,hemoglobin ≥9 gm/L; Glucose >3.3 mmol/L, sodium >130 mmol/L, calcium >2.0 mmol/L. Plasma cortisol and ACTH levels that are not suggestive of adrenal insufficiency. Normal electrocardiogram (ECG) with QTc ≤450 msec for men and ≤470 msec for women. Female subjects of childbearing potential must have a negative pregnancy test within 7 days prior to first study drug administration. Group B: Age ≥18 years at the time of informed consent. Male and female subjects with confirmed HER2+ (IHC 3+ or IHC 2+/FISH+) adenocarcinoma of the breast with advanced disease that have had disease progression on at least 1 standard hormonal or chemotherapy regimen for advanced metastatic breast cancer. Advanced disease will be defined as metastatic disease or locally advanced disease that is surgically unresectable and considered unmanageable with standard therapies such as radiation or systemic therapies. Subjects must have progressed either within 3 months following last dose of adjuvant trastuzumab treatment or progressed following trastuzumab based therapies for metastatic disease. Measurable disease by RECIST or evaluable nonmeasurable disease ECOG ≤2. Required Laboratory Values: ANC ≥1500 cells/mm3,platelet count ≥100,000 cells/mm3,hemoglobin ≥9 gm/L; Glucose >3.3 mmol/L, sodium >130 mmol/L, calcium >2.0 mmol/L. Plasma cortisol and ACTH levels that are not suggestive of adrenal insufficiency. Normal ECG with QTc ≤450 msec for men and ≤470 msec for women. Female subjects of childbearing potential must have a negative pregnancy test within 7 days prior to first study drug administration. Exclusion Criteria: Group A: Prior antitumor therapies including prior experimental agents or approved antitumor therapies, within 1 month. Active infection requiring intravenous (IV) antibiotic treatment. History of prior malignancies within the past 5 years with the exception of curatively treated basal or squamous cell carcinomas of the skin or carcinoma in situ of the cervix. Concurrent severe or uncontrolled diabetes and/or other medical disease Problems with swallowing or malabsorption. History of major surgery to small intestine. Prior treatment with Hsp90 inhibitors. History of central nervous system (CNS) metastasis. Group B: Prior antitumor therapies, including prior experimental agents or approved antitumor therapies, within 1 month. Active infection requiring intravenous (IV) antibiotic treatment. History of prior malignancies within the past 5 years with the exception of curatively treated basal or squamous cell carcinomas of the skin or carcinoma in situ of the cervix. Concurrent severe or uncontrolled diabetes and/or other medical disease Problems with swallowing or malabsorption. History of major surgery to small intestine. Cardiac left ventricular function with resting ejection fraction <50%, assessed by either ECHO or MUGA. Prior treatment with Hsp90 inhibitors. Diabetes treated with insulin. History of CNS metastasis. Please refer to: www.biogenideconcology.com Please refer to the clinicaltrials.gov website for further details on the study: http://clinicaltrials.gov/ct2/show/NCT00412412 To contact Biogen, click here.

Hormone Receptor Positive Metastatic Breast Cancer (HR+ mBC) BIIB021 Plus Aromasin Schedule This study is currently recruiting participants. Purpose To assess the efficacy safety and tolerability of 2 dosing regimens of BIIB021 in combination with exemestane in women whose HR+ breast cancer had progressed following treatment with a nonsteroidal aromatase inhibitor (AI). Study Design:  Treatment, Randomized, Open-label, Parallel Assignment, Safety/Efficacy Study   Official Title: Phase 2a, Open-Label, Randomized, Noncomparative Study of BIIB021 in Combination with Exemestane in Women with Hormone Receptor-Positive, Advanced Metastatic Breast Cancer Who Have Progressed on a Nonsteroidal Aromatase Inhibitor Further study details as provided by Biogen Idec: Primary Outcome Measures: To assess the efficacy of 2 dosing regimens of BIIB021 in combination with exemestane in women whose HR+ breast cancer had progressed following treatment with a nonsteroidal AI. Secondary Outcome Measure: To evaluate the safety and tolerability of BIIB021 in combination with exemestane in this study population.   Estimated Enrollment:   80 Study Start Date:   November 2009 Estimated Study Completion Date:   September 2011 Estimated Primary Completion Date:   April 2011   Eligibility Ages Eligible for Study:   18 Years and older Genders Eligible for Study:   Female Accepts Healthy Volunteers:   No Criteria Inclusion Criteria: Age 18 years of age. Must have histologically or cytologically confirmed estrogen receptor- positive or progesterone receptor-positive, incurable, locally advanced, or metastatic breast cancer. Must have disease progression during treatment with a nonsteroidal AI for locally advanced or metastatic disease, or relapse during treatment or within 12 months of discontinuation of treatment in the adjuvant setting. Must be a postmenopausal female. Must have measurable or evaluable disease. Measurable disease is defined as >=1 lesion with a diameter of >=10 mm. Evaluable disease is defined as bone lesions evaluable by plain X ray, CT scan, or MRI. Lesions identified only by radionuclide bone scan are not allowed. One prior chemotherapy regimen for advanced mBC is allowed. Prior radiotherapy is allowed. Must be able to swallow and retain oral medication. ECOG performance status of <=2. Required laboratory values: Plasma cortisol and adrenocorticotropic hormone (ACTH) levels that are not suggestive of adrenal insufficiency unless on replacement therapy for known adrenal insufficiency. Exclusion Criteria: HER2 overexpressing tumor. History of central nervous system (CNS) metastasis. Previous treatment with exemestane or treatment with an Hsp90 inhibitor. Use of proton pump inhibitors. Known history of or positive test result for hepatitis B or C or HIV. History of gastrectomy or major surgery to small intestine. Please refer to: www.biogenideconcology.com Please refer to the clinicaltrials.gov website for further details on the study: http://www.clinicaltrials.gov/ct2/show/NCT01004081 To contact Biogen, click here.