Clinical Trials

Consecutively enrolled eligible women will be randomized into one of two different treatment groups: 1) Group receiving BTX-A, and 2) Group receiving a placebo. All consenting subjects will be assigned to receive during surgery either a single injection of 100 units of BTX-A, or a placebo (saline water), in the pectoralis major muscle on the operated side once the mastectomy and the breast reconstruction have been completed. Expected duration of subject participation is up to 12 months, depending on the number of tissue expansion visits necessary to fill the tissue expander to its final desired volume.

PRIMARY OBJECTIVES: I. To determine the effect of chemotherapy in patients with node positive breast cancer who do not have high Recurrence Scores (RS) by Oncotype DX. In patients with 1-3 positive nodes, and hormone receptor (HR)-positive, human epidermal growth factor receptor (HER)2-negative breast cancer with RS =< 25 treated with endocrine therapy we will test whether the difference in disease-free survival for patients treated with chemotherapy compared to no chemotherapy depends directly on the magnitude of RS. If benefit depends on the RS score, the trial will determine the optimal cutpoint for recommending chemotherapy or not. SECONDARY OBJECTIVES: I. To compare overall survival (OS), distant disease-free survival (DDFS), and local disease-free interval (LDFI) by receipt of chemotherapy or not and its interaction with RS. II. To compare the toxicity across the treatment arms. III. To perform other assays or tests (in particular the PAM50 risk of relapse score) as they are developed and validated that measure potential benefit of chemotherapy and compare them to Oncotype DX. IV. To determine the impact of management with Oncotype DX on patient-reported anxiety (co-primary Health-Related Quality of Life [HRQL] outcome) prior to screening, after disclosure of test results, and during the randomized trial. V. To determine the impact of Oncotype DX on the initial management cost of node-positive, HR-positive, HER2-negative breast cancer. VI. To compare patient-reported utilities (e.g., QOL) for those randomized to chemotherapy versus no chemotherapy. VII. To estimate the cost-effectiveness of management with Oncotype DX vs usual care using modeling and DFS information from the trial. VIII. To determine the role of other assays (e.g., PAM50) as predictors of DFS, DDFS, and LDFI of patients randomized to chemotherapy versus no chemotherapy. IX. To determine the impact of treatment with chemotherapy versus no chemotherapy on patient-reported fatigue and cognitive concerns (secondary HRQL outcomes). X. To determine the impact of management with Oncotype DX on patient-reported decision conflict, perceptions regarding Oncotype DX testing, and survivor concerns prior to screening, after disclosure of test results, and during the randomized trial (secondary HRQL outcomes). OUTLINE: This is a multicenter study. Patients are stratified according to Recurrence Score (0-13 vs 14-25), menopausal status (pre-menopausal vs post-menopausal), and type of nodal dissection (axillary lymph node dissection [with or without sentinel node mapping] vs sentinel node biopsy without axillary lymph node dissection). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive a protocol-approved chemotherapy regimen based on the patient and/or physician preference. Patients then receive a protocol-approved adjuvant endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity. Patients may complete health-related quality-of-life (QOL) questionnaires at baseline and periodically during study. Information on Medicare and/or insurance coverage and on health coverage decisions may also be collected periodically. After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for at least 15 years.

OBJECTIVES:

     Primary

       -  To estimate the mean change in MRI tumor volume from pretreatment to completion of preoperative endocrine therapy in estrogen receptor-positive (ER+) ductal carcinoma in situ (DCIS), as well as to determine whether 3-month change in volume correlates with 6-month change.

     Secondary

       -  To assess radiographic-pathologic correlation between MRI findings and histopathology, including the prevalence of occult invasive cancer in patients undergoing neoadjuvant endocrine therapy for DCIS.

       -  To compare changes in MRI maximum lesion diameter and mammographic extent at baseline and following treatment.

       -  To determine practice patterns of adjuvant hormonal and radiation therapy in patients who complete neoadjuvant letrozole therapy for DCIS.

       -  To determine whether Ki67 is reduced with neoadjuvant letrozole treatment for DCIS, and to compare the reduction in proliferation between radiographic responders and non-responders.

       -  To identify baseline IHC and expression biomarkers predictive of response to treatment, with response determined by extent of Ki67 reduction.

       -  To examine whether germline polymorphisms are associated with clinical endpoints, including treatment-related toxicity or efficacy outcomes, or with expression of biomarkers in serum or tumor.

       -  To assess quality-of-life and musculoskeletal symptoms associated with neoadjuvant letrozole for ER+ DCIS.

     OUTLINE: This is a multicenter study.

     Patients receive neoadjuvant letrozole orally (PO) once daily (QD) for 3 months. Patients then undergo MRI with an IV contrast. Patients with progressive disease discontinue letrozole and undergo surgery. Patients with complete, partial, or stable disease continue letrozole PO QD for an additional 3 months before undergoing another MRI and surgery. Patients continue receiving letrozole until the day before surgery.

     Surgery (mastectomy or lumpectomy) must be performed within 30 days of the 3- or 6-month MRI.

     Patients' core biopsy specimen and surgical excision specimen may be collected for correlative studies.

     Patients may complete the Menopause Specific Quality-of-Life Questionnaire (MEMOQOL), the Brief Pain Inventory (BPI-SF), the Functional Assessment of Cancer Therapy - General (FACT-G), the Self-Efficacy for Coping with Side Effects, the Medication Taking Behavior (MMAS), and the Beliefs about Medicines Questionnaires at baseline and periodically during study.

     After completion of study therapy, patients are followed up at 1, 3, and 6 months.

Patients who are suspected to have DCIS based on mammographic findings will be invited to participate in this study.  The investigators plan to recruit 200 patients who are scheduled to undergo a breast biopsy for a breast lesion considered suggestive or highly suggestive of DCIS as determined by a radiologist specializing in breast imaging.  Each patient will have a suspicious area of calcification on mammography of extent < 3 cm, or a non-focal area of abnormality on ultrasound or MRI that is scheduled for evaluation by biopsy.  Each patient will undergo an MBI study immediately prior to biopsy.  The study coordinator will approach these patients and inform them of the research project. If they are interested in participating, informed consent will be obtained and the patient will be scheduled for the MBI study prior to the breast biopsy.

This is a multicenter, international, randomized, double-blinded, placebo-controlled, Phase II trial. Patients with advanced or Metastatic Breast Cancer (MBC) who have previously received treatment with an aromatase inhibitor. Patients will receive treatment with GDC-0941 + fulvestrant or GDC-0980 + fulvestrant or placebo + fulvestrant.

OBJECTIVES:

     Primary

       -  To evaluate change in mammographic density using the Boyd method after one year of vitamin D supplementation compared to placebo in premenopausal women.

     Secondary

       -  To explore changes in the serum biomarker IGF1 in response to one year of vitamin D or placebo supplementation in premenopausal women.

       -  To explore changes in cellular proliferation (atypia and Ki67) in response to one year of vitamin D or placebo supplementation in premenopausal women.

       -  To explore correlations between change in breast cancer biomarkers (density, IGF1, atypia, and Ki67) with each other and with change in vitamin D levels.

       -  To compare methods of mammographic density analysis.

       -  To validate a recently developed sunlight questionnaire.

     OUTLINE: This is a multicenter study. Patients are stratified according to baseline vitamin D (sufficient [≥ 30 ng/mL or ≥ 75 mmol/L] vs insufficient [< 30 ng/mL or < 75 mmol/L]) and institutional random periareolar fine-needle aspiration (RPFNA) status (performs RPFNA vs does not perform RPFNA). Patients are randomized to 1 of 2 treatment arms.

       -  Arm I: Patients receive oral placebo once daily for 12 months.

       -  Arm II: Patients receive oral vitamin D (2000 IU) once daily for 12 months. Tissue and blood samples are collected at baseline and at 12 months for laboratory biomarker analysis. Patients also complete questionnaires at baseline and at 12 months.

The purpose of this study is to compare two types of radioactive drugs to see if they provide the same or different information about any disease that may be present in the participants breast.

I-SPY 2 will compare the efficacy of novel drugs in combination with standard chemotherapy with the efficacy of standard therapy alone. The goal is identify improved treatment regimens for subsets on the basis of molecular characteristics (biomarker signatures) of their disease. As described for previous adaptive trials, regimens that show a high Bayesian predictive probability of being more effective than standard therapy will graduate from the trial with their corresponding biomarker signature(s). Regimens will be dropped if they show a low probability of improved efficacy with any biomarker signature. New drugs will enter as those that have undergone testing are graduated or dropped.

PRIMARY OBJECTIVES:

     I. To determine the safety profile of a peptide-based vaccine targeting HER-2/neu, in patients with stage II/III HER-2 positive breast cancer.

     II. To determine the ability of this vaccination protocol to elicit an immune response as measured by activated HER-2/neu-specific T lymphocytes or high-affinity antibodies.

     SECONDARY OBJECTIVES:

     I. To compile descriptive follow-up data regarding vital status and disease recurrence.

     II. To determine if HER-2/neu peptide 885 generates a T cell response that is specific to HER-2/neu or is cross-reactive with epidermal growth factor receptor (EGFR) protein.

     III. To determine if the human leukocyte antigen (HLA)-DR epitopes contain HLA class I embedded epitopes.

     OUTLINE:

     Patients receive HER-2/neu peptide vaccine intradermally (ID) every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

     After completion of study treatment, patients are followed up for up to 2 additional years.

The study is designed as an open-label, randomized, parallel, two arm, multicenter, international Phase 3 study in patients with recurrent or metastatic breast cancer previously treated with cytotoxic chemotherapy regimens. The primary study objective is to compare overall survival of patients who receive NKTR-102 given once every 21 days to patients who receive treatment of Physician's Choice selected from a list of seven single-agent intravenous therapies.