Clinical Trials

This is a Phase IIb/III randomized, double-blind, placebo-controlled study to compare the efficacy and safety of first-line therapy combined with TG4010 or placebo in stage IV non-small cell lung cancer (NSCLC). TG4010 is a suspension of recombinant Modified Vaccinia virus strain Ankara (MVA strain) carrying coding sequences for human MUC1 antigen and human interleukin-2 (IL2). TG4010 has been developed for use as an immunotherapy in cancer patients whose tumors express the MUC1 antigen. TG4010 is intended to induce a MUC1-specific cellular immune response and to produce a non-specific activation of several components of the immune system.

Chronic dizziness and recurrent vertigo are frequent complaints in primary and specialty medical care settings.  Two common causes of these symptoms are vestibular migraine (VM) and chronic subjective dizziness (CSD), which may be seen in up to 25% of patients examined in tertiary neurotology centers.  However, VM and CSD are relatively new diagnoses that have not yet been validated.  Furthermore, recent research found that they co-exist 30% of the time with overlap in several features.  From a clinical standpoint, this makes it difficult to diagnose and treat them well.  From a research standpoint, it confounds subject selection for mechanistic investigations.

     The primary goal of this study to dissect VM and CSD in order to identify the key features and clarify the diagnostic criteria of each condition.  Fifty patients diagnosed with coexisting VM-CSD will be treated with either verapamil or sertraline.  Based on clinical and research experience to date, verapamil is thought to have greater effect on migraine-related symptoms, whereas sertraline is thought to have greater effect on CSD-related symptoms.  It is hypothesized that a differential treatment response to these two pharmacologic probes will help to tease apart the unique clinical features of VM and CSD and identify risk factors that are shared or separate between the two conditions.  The different mechanisms of action of the two study medications may also shed light on the physiologic underpinnings of VM and CSD.

     This project will be a 14-week, prospective, randomized, double-blind, parallel group, pharmacologic dissection trial.  A 12-week treatment period will follow 2 weeks of baseline observation.  Patients will chart daily headache and vestibular symptoms.  VM and CSD symptoms and potential confounds such as anxiety and depression will be measured at two week intervals.  Data will be analyzed for differential and shared treatment effects that align with or oppose current concepts of VM and CSD.

The purpose of this study is to determine the proportion of confirmed responses (complete response, partial response, and hematologic improvement as defined by revised IWG criteria during the 12 months of treatment.

PRIMARY OBJECTIVES: I. To determine the maximally tolerated dose of AZD2171 (cediranib) in combination with AZD6244 hydrogen sulfate. II. To describe the toxicity profile associated with AZD2171 (cediranib) in combination with AZD6244 hydrogen sulfate. III. To describe the tumor responses and identify any activity of this AZD2171 (cediranib) in combination with AZD6244 hydrogen sulfate. IV. To explore, through correlative studies, the effect of AZD2171 (cediranib) with or without AZD6244 hydrogen sulfate on serum markers of apoptosis. V. To assess the pharmacokinetic interaction of AZD2171 (cediranib) in combination with AZD6244 hydrogen sulfate. VI. To study the association of clinical (toxicity and/or tumor response or activity) with the pharmacologic (pharmacokinetic/pharmacodynamic) parameters, and/or biologic (correlative laboratory study) results. OUTLINE: This is a dose-escalation study followed by a dose-expansion cohort study. Patients receive cediranib maleate orally (PO) once daily and selumetinib PO once or twice daily on days 1-28 (days 8-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Some patients undergo blood sample collection at baseline and periodically during study for correlative studies. After completion of study therapy, patients are followed up at 3 months.

The purpose of this study is to evaluate safety and tolerability as well as the effects of RM-131 on colonic transit, bowel consistency, bowel habits, abdominal pain, and other abdominal symptoms in patients with chronic constipation.

OBJECTIVES:

     Primary

       -  To assess tumor response in patients with relapsed or refractory low-grade follicular lymphoma (grade I or II), mantle cell lymphoma, or lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia) treated with rituximab, cyclophosphamide, bortezomib, and dexamethasone.

     Secondary

       -  To evaluate overall survival, progression-free survival, duration of response, and time to treatment failure in patients treated with this regimen.

       -  To describe the adverse event profile (as assessed by NCI CTCAE version 3.0) of this regimen in these patients.

       -  To evaluate the quality of life, in terms of patient-reported neurotoxicity, in patients treated with this regimen.

     OUTLINE: Patients receive rituximab IV on day 1, bortezomib IV on days 1, 4, 8, and 11, and oral cyclophosphamide and oral dexamethasone on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

     Patients complete a quality of life questionnaire (FACT/GOG neurotoxicity questionnaire, version 4.0) at baseline, on day 1 of courses 3, 6, and 9, and at the completion of study treatment.

     After completion of study treatment, patients are followed every 3-6 months for up to 5 years.

PRIMARY OBJECTIVES:

     I. To establish the safety and efficacy of pazopanib hydrochloride in patients with differentiated, medullary, or anaplastic thyroid cancer.

     SECONDARY OBJECTIVES:

     I. To assess the impact of pazopanib hydrochloride on serum and plasma VEGF levels.

     II. To explore the potential relationship between changes in thyroglobulin levels and tumor response in patients with advanced differentiated thyroid cancer known to be thyroglobulin antibody negative.

     OUTLINE:

     Patients receive pazopanib hydrochloride orally (PO) once daily (QD) 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 for 6 months or until 3 years after registration.

Patients randomized to RIC will receive one of two regimen types: the combination of fludarabine (120-180 mg/m^2) and busulfan (less than or equal to 8 mg/kg or IV equivalent) (Flu/Bu) or fludarabine (120-180 mg/m^2) and melphalan (less than 150 mg/m^2) (Flu/Mel). Patient randomized to MAC will receive one of three regimens: busulfan (16 mg/kg oral or 12.8 mg/kg IV equivalent) and cyclophosphamide (120 mg/kg) (Bu/Cy); or, busulfan (16 mg/kg PO or 12.8 mg/kg IV) and fludarabine (120-180 mg/m^2) (Bu/Flu); or, cyclophosphamide (120 mg/kg) and total body irradiation (greater than 1200-1420cGy) (CyTBI). A total of 356 patients (178 to each arm) will be accrued on this study over a period of four years. Patients will be followed for up to 18 months from transplantation.

Functional (psychogenic or somatoform) symptoms are commonly observed in neurology clinics. There is no known empirically validated treatment approach to functional symptoms. Cognitive Behavioral Therapy (CBT) can be effective, but there are major obstacles to its provision. The investigators will test the hypothesis that adding a CBT-based guided self-help (GSH) as compared to treatment as usual (TAU) improves patient outcomes.

The study objective is to gather post-market clinical data on the use of the CentriMag RVAS when used for temporary mechanical circulatory support of the right ventricle in patients with acute right ventricular failure from any cause