Clinical Trials

The purpose of this study is to examine the safety and evaluate the response of VB-111 on DTC.

OBJECTIVES: Primary - To determine whether administering high-dose thoracic radiotherapy, 70 Gy (2 Gy once daily over 7 weeks) or 61.2 Gy (1.8 Gy once daily for 16 days followed by 1.8 Gy twice daily for 9 days), will improve median and 2-year survival compared with 45 Gy (1.5 Gy twice daily over 3 weeks) in patients with limited-stage small cell lung cancer. Secondary - To compare treatment-related toxic effects of thoracic radiotherapy regimens in patients with limited-stage small cell lung cancer. - To compare response rates, failure-free survival, and toxicity of thoracic radiotherapy regimens in patients with limited-stage small cell lung cancer. - To compare rates of local relapse, distant metastases, and brain metastases with these regimens. - To describe the patterns of use of thoracic intensity-modulated radiotherapy (IMRT) in patients with limited-stage small cell lung cancer. OUTLINE: This is a 2-part, multicenter, randomized study. Patients are stratified according to gender, weight loss 6 months prior to study entry (≤ 5% of body weight vs > 5% of body weight), ECOG performance status (0 vs 1 vs 2), radiotherapy technique (intensity-modulated radiotherapy vs 3-dimensional conformal radiotherapy), and radiotherapy start time (at first course of protocol chemotherapy, after one course of prior non-protocol chemotherapy vs at first course of protocol chemotherapy, without prior non-protocol chemotherapy vs at second course of protocol chemotherapy, without prior non-protocol chemotherapy). - Part 1: Patients are randomized to 1 of 3 treatment arms. - Arm I: Patients undergo standard-dose (45 Gy given in 30 treatments) thoracic radiotherapy twice daily, 5 days a week, for 3 weeks. Patients also receive cisplatin IV on day 1 and etoposide IV on days 1, 2, and 3. - Arm II: Patients undergo higher-dose (70 Gy given in 35 treatments) thoracic radiotherapy once daily, 5 days a week, for 7 weeks. Patients also receive cisplatin and etoposide as in arm I. - Arm III: (discontinued as of 03/10/13) Patients undergo higher-dose (61.2 Gy given in 34 treatments) thoracic radiotherapy once daily, 5 days a week, during the initial 16 days (approximately 3 weeks) of treatment and then twice daily, 5 days a week, for the final 9 days (approximately 2 weeks) of treatment. Patients also receive cisplatin and etoposide as in arm I. In all arms, treatment with cisplatin and etoposide repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. - Part 2: An interim analysis was conducted after accrual of 30 patients per arm and one experimental arm based upon a comparison of treatment-related toxicity was selected. The most toxic experimental arm was discontinued, and the trial continues comparing standard therapy (arm I) to the selected experimental regimen (arm II) as described in part 1. Prophylactic radiotherapy: Within 3-6 weeks after completion of chemotherapy, patients with responding disease are eligible to undergo prophylactic radiotherapy to the brain once a day, 5 days a week, for 2 weeks. After completion of study treatment, patients are followed up at least every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years or until disease progression. At disease progression, patients are followed up every 6 months.

PRIMARY OBJECTIVES:  I. To determine the progression-free survival of erlotinib (erlotinib) and bevacizumab versus that of erlotinib alone for the purpose of deciding if the combination arm is worth pursuing in a phase III trial.  SECONDARY OBJECTIVES:  I. To investigate the overall survival of erlotinib and bevacizumab versus erlotinib alone. II. To investigate the response rate of erlotinib and bevacizumab versus erlotinib alone. III. To investigate the progression-free survival in patients with exon deletion 19 or exon 21 L858R EGFR point mutations. IV. To investigate the toxicity of erlotinib and bevacizumab versus erlotinib alone using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. TERTIARY OBJECTIVES:  I. To correlate EGFR mutations detected in plasma deoxyribonucleic acid (DNA) with those detected in tumor DNA. II. To estimate the prevalence of EGFR T790M resistance mutations from pretreatment tumor biopsies using more sensitive mutation detection methods. III. To investigate progression free survival of EGFR mutant NSCLC patients with and without concurrent EGFR T790M detected from pre-treatment tumor specimen using allele specific quantitative polymerase chain reaction (PCR). IV. To prospectively evaluate the predictive value of plasma vascular endothelial growth factor A (VEGF-A) levels on progression free survival in patients treated with erlotinib alone or in combination with bevacizumab.  OUTLINE: Patients are randomized to 1 of 2 treatment arms.   ARM A: Patients receive erlotinib orally (PO) once daily (QD) on days 1-21.  ARM B: Patients receive erlotinib as in Arm A and bevacizumab intravenously (IV) over 30-90 minutes on day 1.   In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.  After completion of study treatment, patients are followed up periodically for up to 5 years.

PRIMARY OBJECTIVES: I. Evaluate the overall and event-free survival of younger patients with newly diagnosed stage I favorable histology Wilms' tumor (< 2 years of age and < 550gms) treated with nephrectomy only (very low risk), or with newly diagnosed stage III favorable histology Wilms tumor with possible nephrectomy followed by vincristine, dactinomycin, doxorubicin hydrochloride, and radiotherapy (standard risk). SECONDARY OBJECTIVES: I. Determine the effects of adding doxorubicin hydrochloride to the regimen for patients with stage I or II favorable histology found to have a high-risk biological marker. II. Determine whether the omission of adjuvant therapy increases the incidence of contralateral kidney lesions in patients with very low-risk disease treated by nephrectomy and observation only. III. Determine whether the omission of adjuvant therapy increases the incidence of renal failure in patients with very low-risk disease who have metachronous relapse. IV. Correlate study outcomes in patients with standard-risk disease with biological data from tissue collections on protocol study COG-AREN03B2. OUTLINE: This is a multicenter study. Patients are stratified according to clinical and biological risk factors (very low risk vs standard risk). STRATUM I: (very low-risk disease) Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks. STRATUM II: (standard-risk, stage I or II disease with adverse biological marker) Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks. STRATUM III: (standard-risk, stage III disease) Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks. After completion of study treatment, patients are followed periodically for up to 8 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:

       -  To study in vivo detection of breast masses by vibro-acoustography (VA) imaging.

       -  To evaluate the performance of VA imaging in differentiating between benign and malignant breast masses identified as BI-RADS 4 or 5.

     OUTLINE: Patients undergo clinical mammography of the breast, followed by vibro-acoustography (VA) imaging using ultrasonography over 90 minutes. Patients may also undergo further imaging using clinical ultrasonography.

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 determine the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) in medically inoperable patients with centrally located stage I non-small cell lung cancer. (Phase I) - To determine the efficacy of SBRT when administered at the MTD in these patients. (Phase I) - To estimate the local control rate of SBRT at the MTD in these patients. (Phase II) Secondary - To estimate the rates of adverse events (other than dose-limiting toxicity) of ≥ grade 3 that is possibly, probably, or definitely related to treatment and that occurs within 1 year after the start of SBRT in these patients. - To estimate the rates of late adverse events (i.e., occurs > 1 year after the start of SBRT) in these patients. - To estimate the local control and progression-free and overall survival rates in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients undergo stereotactic body radiotherapy every 2 days over 1½-2 weeks (total of 5 fractions) in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically.

PRIMARY OBJECTIVES: I. Classify patients with renal tumors by histological categorization, surgico-pathological stage, presence of metastases, age at diagnosis, tumor weight, and loss of heterozygosity for chromosomes 1p and 16q, to define eligibility for a series of therapeutic studies. II. Maintain a biological samples bank to make specimens available to scientists to evaluate additional potential biological prognostic variables and for the conduct of other research by scientists. SECONDARY OBJECTIVES: I. Monitor outcome for those patients who are not eligible for a subsequent therapeutic study. II. Describe whether the pulmonary tumor burden correlates with outcome in patients with stage IV disease. III. Describe the sensitivity and specificity of abdominal computed tomography (CT) scan by comparing it with surgical and pathologic findings for identification of local tumor spread beyond the renal capsule to adjacent muscle and organs, lymph node involvement at the renal hilum and in the retroperitoneum, preoperative tumor rupture, and metastases to the liver. IV. Compare the sensitivity and specificity of pre-operative abdominal CT scan and MRI for the identification and differentiation of nephrogenic rests and Wilms' tumor in children with multiple renal lesions. V. Correlate the method of conception (natural vs assisted reproductive technology) with the development of Wilms' tumor. OUTLINE: This is a multicenter study. Tumor tissue, blood, and urine samples are collected for research studies, including immunohistochemistry. CT scans and magnetic resonance imaging (MRIs) are also performed. Loss of heterozygosity analyses (chromosome 1p and 16q) are performed by extraction of DNA. DNA polymorphisms are assayed by polymerase chain reaction using standard methodology. Leftover specimens are archived for future studies. Patients are followed periodically for 5 years.