Clinical Trials

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.

This is a multicenter, open-label, Phase 2 study. Subjects will be randomized to either the investigational product, DN24-02, or to standard of care. The purpose of this study is to compare the length of survival between these 2 groups of subjects. Other purposes of the study are to learn about the safety of DN24-02, to learn if it delays the time until urothelial cancer recurs, and to learn if the immune system responds to treatment with DN24-02. All subjects will be followed for this study for the remainder of their lives.

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.

This is an open-label study that investigates the impact of a dose ramp-up strategy for sorafenib in patients with HCC. Clinical trial and post-marketing data suggest that sorafenib dose reductions and discontinuations due to adverse events are common and limit the drug's effectiveness. It is our hypothesis that a dose escalation strategy for sorafenib will improve the tolerability and allow a greater percentage of patients to remain on drug. The primary end-point of the study is the total accumulated and median daily dose of sorafenib delivered at month 2 and 4.

Patients will be identified and enrolled from Thoracic Surgical Clinics. A preoperative bronchoscopy will be performed to obtain systematic bronchial biopsies from defined proximal airway sites. Patients will then undergo surgical resection and tumor tissue and normal lung specimens collected. For patients with bronchial dysplasia postoperatively, starting less than 90 days from the time of surgery, patients will be randomized to receive either 850 mg po BID of metformin or observation. Metformin dosing will include a 4 week ramp up of 850 mg po daily prior to starting the BID dose. Adjuvant platinum-based chemotherapy will be applied at the discretion of treating physicians.  Patients found to have bronchial dysplasia at the time of bronchoscopy will undergo follow up bronchoscopy and tissue sampling at 6 months follow up.

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: Primary - To collect clinical data and family histories and blood and/or tissue samples from patients diagnosed with pancreatic diseases, including pancreatic cancer, for use in future studies. - To collect information regarding food preparation and intake in these patients. Secondary - To make available to researchers medical data and biospecimens to enable them to develop better ways to screen people at risk for pancreatic conditions, including pancreatic cancer. - To investigate genes or substances that increase susceptibility of developing pancreatic conditions. - To find agents that may help prevent, treat, or cure these conditions. - To learn whether inherited factors increase the risk of pancreatic diseases, pancreatic cancer, or other cancers. OUTLINE: This is a multicenter study. Patients complete two 1-hour surveys assessing health, clinical and family history of pancreatic conditions including cancer, and food preparation and intake. Patients also complete a 15- to 30-minute follow up survey at 6 months and 1 year to assess health, health practices, and family history. A review of the patient's medical information is obtained from the medical record. Blood samples are collected for future research studies. Oral cells and stool samples may also be collected for future studies.

OBJECTIVES: - To collect clinical history, family history, and blood and/or tissue samples from family members of patients diagnosed with pancreatic diseases, pancreatic cancer, or melanoma. - To learn whether inherited factors increase the risk of pancreatic diseases, pancreatic cancer, or other cancers. OUTLINE: Study participants undergo collection of blood and/or tissue samples as well as survey data for inclusion in a familial data and tissue registry. Participants complete two baseline surveys regarding their personal, family, health, and environmental exposure histories and regarding their opinions on cancer and cancer screening. Patients also complete a follow-up survey at 1 year and undergo review of their medical records.