Clinical Trials

A total of 150 patients will be studied. Each patient will have a suspicious lesion on mammogram, ultrasound or breast magnetic resonance imaging (MRI) for which biopsy is scheduled. The lesion size on mammogram, ultrasound or breast MRI must be less than 2 cm in diameter and must be considered "suspicious" or "highly suspicious" for malignancy. Following injection of 8 mCi Tc-99m sestamibi, all patients will undergo craniocaudal (CC) and mediolateral oblique (MLO) views of each breast using a molecular breast imaging (MBI) system incorporating the latest hardware and software algorithms. Each image will be acquired for 10 minutes in dynamic mode as 4 x 2.5 minute images. Summation of a given number of frames from each acquisition will yield images of an increasing mCi dose. Hence with an 8 mCi injection and a dynamic acquisition mode, we can evaluate the sensitivity of MBI as a function of administered doses of Tc-99m sestamibi ranging from 2 to 8 mCi. The thickness of the breast will be recorded to determine its relevance to lesion detectability.

     Patient Selection

     The goal of this study is to enroll 150 female patients in this study. The rationale for a study number of 150 patients is given in Appendix D. Patients referred for a mammogram, ultrasound or breast MRI study at Mayo Clinic Rochester will be considered for the study if they meet the following criteria:

       -  Have a lesion on mammogram, ultrasound or breast MRI that measured < 2 cm and is considered suspicious or highly suggestive of malignancy according to the Breast Imaging Reporting and Data System Atlas criteria (BI-RADS 4 or 5). (Note: while 2 cm is larger than the desired lesion size that we wish to study, this limit was recommended by our radiology colleagues as estimates of lesion size from mammography, ultrasound and MRI are not exact)

       -  Are scheduled for biopsy (needle and/or surgical biopsy) of the suspicious lesion

       -  Are > 18 years of age

       -  Had a negative pregnancy test or must be postmenopausal or surgically sterilized

     Eligible patients will be offered enrollment if the time interval between mammogram, ultrasound or MRI and scheduled biopsy allows for performance of MBI. Patients with prior needle biopsy of the lesion will be excluded from this study, as such biopsies may effectively remove all or part of the lesion. Prospective patients will be identified by the radiologist based on findings in their mammographic, ultrasound or MRI studies.

OBJECTIVES:

       -  To examine the changes in the plasma concentrations of the hydroxylated metabolite, 4-hydroxy tamoxifen, and endoxifen in women with known or at high risk for developing breast cancer who are receiving selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor therapy comprising venlafaxine, citalopram hydrobromide, escitalopram oxalate, gabapentin, or sertraline hydrochloride for the treatment of hot flashes, depression, or any other medically indicated condition.

       -  To evaluate whether genetic variants known to affect the activity of CYP2D6, SULT1A1, and other drug metabolizing enzymes (e.g., UGT's) involved in the biotransformation of tamoxifen citrate affect the plasma concentrations of the hydroxylated metabolites, 4-hydroxy tamoxifen and endoxifen.

     OUTLINE: This is a multicenter study.

     Patients receive oral tamoxifen citrate and concurrent selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) therapy comprising oral venlafaxine, citalopram hydrobromide, escitalopram oxalate, sertraline hydrochloride, or gabapentin for 8-24 weeks. Treatment continues in the absence of disease progression.

     Blood samples are obtained at baseline and after completion of study therapy. Samples are evaluated by pharmacokinetic analysis to determine the effects of SSRI/SNRI study drugs on plasma concentrations of tamoxifen and its metabolites. Plasma levels of tamoxifen citrate, N-desmethyl tamoxifen, 4-OH tamoxifen, and endoxifen are measured using reverse phase high performance liquid chromatography. Blood samples are also analyzed by CYP2D6 genotyping to test for CYP2D6 gene variation (i.e., *3, *4, *6, *10, *17, and *41) in genes that encode tamoxifen-metabolizing enzymes. Additional CYP2D6 alleles, including gene duplication and gene deletion (*5) are assessed.

This proposal describes a community-based participatory research study to develop and pilot test a new behavioral intervention to promote mammography screening among Navajo women. From a public health perspective, the intervention has the potential to reach many Navajo women, as 80% of women scheduled for mammography appointments do not follow through.  These women (over 1,500 each year) are referred to the Nation Breast and Cervical Cancer Prevention Program (NNBCCPP).  A key barrier toward implementing cancer prevention and control efforts in the Navajo community is a lack of cancer literacy or cultural and conceptual knowledge regarding cancer.  Other barriers to screening are fear of cancer, stigma of cancer (even talking about cancer) often experienced by the patient, family and community, and lack of knowledge about the etiology of cancer and importance of early detection.  Therefore, communication about cancer is impeded within Navajo families and the community.

     This proposal builds on our successful partnership and collaboration with Diné College (the Navajo tribal college).  The proposed study is designed to assess the feasibility and potential efficacy of a cancer-literacy focused, family-based intervention on completion of mammography screening for Navajo women.  The intervention will include culturally and linguistically appropriate educational materials about cancer (e.g., the Navajo Cancer Glossary).  The project will be implemented in two phases.  During Phase 1, the investigators will develop the family cancer literacy intervention with feedback from our community advisory committee.  In addition, the Cancer Literacy Measure will be adapted for Navajo women through focus groups and individual interviews.  Phase 2 will consist of a formative evaluation of the intervention.  The NNBCCPP patient and a female family member will be randomly assigned in pairs to the control condition (existing NNBCCPP health education services, N=40 pairs) or to receive these health education services plus the family cancer literacy intervention (N=40 pairs).  The investigators  will assess the intervention's feasibility and acceptability as indicated by the recruitment and retention rates and qualitative ratings of treatment acceptability.  In addition, the investigators will examine the effect of the intervention compared with the control group on the proportion of women who complete mammography screening at 3-month follow-up documented by NNBCCPP records.   The investigators will also examine changes in Cancer Literacy Measure scores from baseline to 3-month follow-up among both patients and family members.  The investigators expect that as a result of this project, the investigators will have developed a replicable, feasible, and acceptable intervention, the efficacy of which can be tested in future large-scale randomized clinical trials.  In addition, the adapted Cancer Literacy Measure could be used in future cancer prevention and control projects within the Navajo Nation.  The overall objective is to reduce breast cancer morbidity and mortality among Navajo women.

PRIMARY OBJECTIVES:

     I. To demonstrate the feasibility of conducting a 10-patient pilot study in asymptomatic ovarian cancer patients with cancer antigen (CA 125) elevation.

     SECONDARY OBJECTIVES:

     I. To explore whether oral gold therapy either stabilizes or lowers the CA 125 level and maintains patients in an asymptomatic state and to provide descriptive data on tumor response and duration of response.

     II. To acquire qualitative data on patients' perceptions of learning of CA 125 elevation.

     III. To explore whether immunohistochemical staining for PKC iota expression in resected tumor samples appears to be associated with clinical outcomes with auranofin.

     OUTLINE:

     Patients receive auranofin orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

     After completion of study treatment, patients are followed up every 6 months for 2 years.

PRIMARY OBJECTIVES:

     I. To Determine the minimal biologic dose of lapatinib ditosylate, defined as the smallest dose, when compared with placebo, that results in a statistically significant lower rate of proliferation in ductal carcinoma in situ (DCIS) breast cancer cells as measured by Ki67.

     II. To determine the toxicity profile and frequency of adverse events in women with DCIS breast cancer taking lapatinib ditosylate at three doses (750 mg, 1,000 mg, and 1,500 mg) as compared with women taking placebo.

     SECONDARY OBJECTIVES:

     I. To determine whether lapatinib ditosylate treatment affects the incidence of DCIS seen at the time of surgical excision.

     II. To determine whether treatment with lapatinib ditosylate will modulate breast tissue histology or the expression of specific biomarkers in normal and DCIS breast cancer cells, including proliferation markers (Ki67 in normal cells), apoptosis marker (cleaved caspase 3), growth factor receptors (EGFR, ErbB2, ErbB3, ErbB4), signal transduction markers (MAPK, phospho-MAPK), hormone receptors (estrogen receptor, progesterone receptor), and p27.

     OUTLINE: This is a multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 4 treatment arms.

     Arm I: Patients receive 1,500 mg of oral lapatinib ditosylate once daily for 2-6 weeks in the absence of disease progression or unacceptable toxicity.

     Arm II: Patients receive 1,000 mg of oral lapatinib ditosylate once daily for 2-6 weeks in the absence of disease progression or unacceptable toxicity.

     Arm III: Patients receive 750 mg of oral lapatinib ditosylate once daily for 2-6 weeks in the absence of disease progression or unacceptable toxicity.

     Arm IV: Patients receive oral placebo once daily for 2-6 weeks in the absence of disease progression or unacceptable toxicity.

     All patients then undergo surgery. Tissue samples from initial breast biopsy and subsequent excisional biopsy are collected for the following biomarker studies: proliferation by measuring Ki67 staining in ductal carcinoma in situ (DCIS) breast cancer cells; proliferation in normal cells; apoptosis marker (cleaved caspase 3) expression and activation; phospho-MAPK activation by immunohistochemistry (IHC); total MAPK expression; peptide growth factor receptors (ErbB1 [EGFR], ErbB2 [HER-2/neu], ErbB3, ErbB4) expression; estrogen receptor and progesterone receptor proliferation and differentiation; and p27 activation.

     After completion of study treatment, patients are followed for 4-5 weeks.

PRIMARY OBJECTIVES: I. To evaluate the efficacy of single agent ABT-888 (veliparib) (NSC 737664) in BRCA carriers with metastatic breast cancer based on response rate (RECIST criteria). SECONDARY OBJECTIVES: I. To conduct subset analysis on BRCA1 vs. BRCA2 and hormone receptor status. II. To evaluate progression-free survival of patients on single-agent ABT-888. III. To further describe the safety and tolerability of ABT-888 (NSC 737664) as a single agent and in combination with carboplatin for BRCA-associated breast cancer. IV. To evaluate the pharmacokinetics of ABT-888 (NSC 737664) alone and in combination with carboplatin. V. To assess the relationship between the level of PARP inhibition by ABT-888 and biomarkers of DNA damage in PBMC's and in tumor VI. To explore the relationship between biomarkers of drug effect and progression-free survival. VII. To evaluate the efficacy and safety of the combination of carboplatin and ABT-888 in patients who have failed single agent ABT-888. VIII. To conduct subset analysis on BRCA1 vs. BRCA2 and hormone receptor status. OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0-1 vs 2), and hormone status (estrogen receptor [ER]- and/or progesterone receptor [PR]-positive vs ER- and/or PR-negative). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive oral veliparib twice daily on days 1-21. ARM II: Patients receive carboplatin IV over 30 minutes on day 1 and veliparib as in arm I. In both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood and hair follicle sample collection for pharmacokinetics and other laboratory studies. After completion of study therapy, patients are followed up every 3-6 months.

OBJECTIVES:

     Primary

       -  To assess the local recurrence (LR) rate with breast-conservation in patients with multiple ipsilateral primary breast cancer (MIBC).

     Secondary

       -  To examine the conversion rate to mastectomy secondary to persistent positive margins; poor cosmesis within the first year of attempting breast-conservation surgery (BCS) or inability to satisfy the radiation dose constraints on the boost to the lumpectomy bed of each site of disease.

       -  To assess patient's perception of cosmesis and incidence of breast lymphedema.

       -  To examine the type and severity of adverse effects of BCS and radiation for women with MIBC.

       -  To examine the radiation-related side effects of whole-breast radiation with a boost to 1 large or > 1 lumpectomy site.

       -  To evaluate protein and gene expression patterns in tissue taken from each breast lesion and to evaluate the concordance of the findings between these lesions.

       -  To compare the extent of disease described on imaging (mammography, bilateral breast magnetic resonance imaging [MRI] and other adjunctive imaging modalities) with surgical findings.

     OUTLINE: This is a multicenter study.

     Patients undergo breast-conserving surgery (BCS) with all lesions resected to negative margins using 1 lumpectomy or 2-3 separate lumpectomy incisions at the discretion of the surgeon. Patients receive adjuvant chemotherapy and/or endocrine therapy at the discretion of the treating medical oncologist based on tumor characteristics.

     Within 6-10 weeks after surgery or 8 weeks after completion of cytotoxic chemotherapy, patients undergo adjuvant whole-breast irradiation (WBI) with a boost to the lumpectomy bed of each site of disease 5 days a week for approximately 6 weeks.

     Patients complete the Breast-Conserving Therapy Module (BREAST-Q© subscales) questionnaire 5-30 days after surgery and every 6 months for the first 2 years and the yearly for the next 3 years after WBI. Patients' surgeons also complete the questionnaire 5-30 days after performing final surgery to assess cosmetic outcomes.

     Formalin-fixed paraffin-embedded (FFPE) tissue block from each site of disease are collected during BCS for protein and gene expression pattern studies. Blood samples may be also collected at baseline and during BCS.

     After completion of study treatment, patients are followed up every 6 months for 2 years and then yearly for years 3-5.

PRIMARY OBJECTIVES: I. To assess the safety of administering a course of cyclophosphamide treatment followed by six subsequent monthly vaccinations with a peptide-based vaccine targeting folate receptor 1 (FR)-alpha (multi-epitope folate receptor alpha peptide vaccine). II. To assess the ability of this vaccination protocol to elicit an immune response as measured by activated FR-alpha-specific T lymphocytes or high-affinity antibodies. CORRELATIVE OBJECTIVES: I. To determine FR-alpha expression status of primary tumors when available as formalin-fixed, paraffin-embedded material and whether expression correlates with the ability to generate an immune response. II. To identify human lymphocyte antigen (HLA) class I binding peptides from FR-alpha that are recognized by lymphocytes from patients prior to and after vaccination. OUTLINE: Patients receive 100 mg cyclophosphamide orally daily for 1 week followed by a 1 week rest, and then another week of cyclophosphamide. Approximately 7-10 days after the last dose of cyclophosphamide, patients receive multi-epitope folate receptor alpha peptide vaccine intradermally (ID) on day 1. Vaccine treatment repeats 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 at 3, 6, and 12 months.

OBJECTIVES: Primary - To determine whether an accelerated course of hypofractionated whole-breast irradiation (WBI) including a concomitant boost to the tumor bed in 15 fractions following lumpectomy will prove to be non-inferior in local control to a regimen of standard WBI with a sequential boost following lumpectomy for early-stage breast cancer patients. Secondary - To determine whether breast-related symptoms and cosmesis from accelerated WBI that is hypofractionated (in only 3 weeks) with a concomitant boost is non-inferior to standard WBI with sequential boost. - To determine whether the risk of late cardiac toxicity in patients with left-sided breast cancer treated with hypofractionation will be non-inferior to conventional fractionated radiation therapy (RT) based upon analysis of radiation dosimetry from CT-based treatment planning and NTCP calculations. - To determine whether CT-based conformal methods intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for WBI are feasible in a multi-institutional setting following lumpectomy in early-stage breast cancer patients and whether dose-volume analyses can be established to assess treatment adequacy and likelihood of toxicity. - To determine that cosmetic results and breast-related symptoms 3 years after hypofractionated breast radiation with concomitant boost will not be inferior to that obtained 3 years after WBI with sequential boost. - To determine whether future correlative studies can identify individual gene expressions and biological host factors associated with toxicity and/or local recurrence from standard and hypofractionated WBI. - If shown to be non-inferior, to then determine if accelerated course of hypofractionated WBI including a concomitant boost to the tumor bed in 15 fractions following lumpectomy will prove to be superior in local control to a regimen of standard WBI with a sequential boost following lumpectomy for early-stage breast cancer patients. - To determine whether treatment costs for hypofractionated WBI with concomitant boost are not higher than WBI with sequential boost. OUTLINE: This is a multicenter study. Patients are stratified according to age (< 50 vs. ≥ 50 years), prior chemotherapy (yes vs. no), estrogen-receptor status (+ vs. -), and histology grade (1-2 vs. 3). Patients are randomized to 1 of 2 treatment arms. Treatment begins within 9 weeks of last surgery or chemotherapy delivery. - Arm I: Patients undergo standard whole-breast radiotherapy (WBI) comprising intensity-modulated radiation therapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) 5 days a week for 3-5 weeks followed by a sequential radiotherapy boost to the lumpectomy area 5 days a week for 1-1½ weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. - Arm II: Patients undergo accelerated hypofractionated WBI comprising IMRT or 3D-CRT with a concurrent boost to the lumpectomy area 5 days a week for 3 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients' tissue samples may be collected for future research studies. After completion of study therapy, patients are followed at 1 month, at 6 months, and then yearly.

OBJECTIVES:

       -  To investigate the safety of replacing complete inguinofemoral lymphadenectomy by adjuvant radiotherapy in early-stage vulvar cancer patients with a sentinel node metastasis ≤ 2 mm.

       -  To evaluate the short- and long-term morbidity associated with the sentinel lymph node procedure and adjuvant (chemo)radiotherapy.

       -  To further establish the safety of omitting complete inguinofemoral lymphadenectomy in patients with a negative sentinel node.

       -  To explore the efficacy, safety, and short- and long-term morbidity of inguinofemoral lymphadenectomy and radiotherapy in patients with sentinel node metastasis > 2 mm. (exploratory)

     OUTLINE: This is a multicenter study.

     Patients undergo planned radical vulvectomy and sentinel lymph node dissection. Patients without lymph node involvement undergo observation. Patients with minimal lymph node involvement undergo radiotherapy. Patients with significant lymph node involvement undergo inguinofemoral lymphadenectomy and radiotherapy with or without chemotherapy according to institutional guidelines.

     After completion of study treatment, patients are followed up every 2 months for 2 years. Follow-up includes interview, gynecological examination, and palpation of the groins.