The patients undergoing elective and complete CABG revascularization performed by the same surgeon, will be randomized in two different groups to receive, in the three days before surgery, Ranolazine at a dose of 375 mg twice daily.

The patients undergoing elective and complete CABG revascularization performed by the same surgeon, will be randomized in two different groups to receive, in the three days before surgery, placebo twice daily.

Myocardial Stunning

Patients in this arm receive Ranolazine at a dose of 375 mg twice daily in the three days before surgery

Ranolazine

Patients receive Placebo twice daily in the three days before surgery

Placebo

Ranolazine a Potential New Therapeutic Application

Ranolazine Myocardial Protection in Complete Coronary Artery Bypass Grafting: A Randomized-controlled Trial

A blood sample will be collected by coronary sinus and the sample sent by our laboratories to assess the concentration in µg/l of cardiac troponins directly in venous blood before cardiopulmonary by-pass and after the release of aortic cross clamp, about 10 minutes after the end of reperfusion.

Earlobe arterialized blood sample will be collected by radial artery coronary sinus and the sample sent by our laboratories to assess the concentration of VO2 and O2ER in ml/min in venous blood before cardiopulmonary by-pass and after the release of aortic cross clamp, about 10 minutes after the end of reperfusion.

Earlobe arterialized blood sample will be collected by radial artery and coronary sinus and the sample sent by our laboratories to assess the concentration of lactates in mmol/L in venous blood before cardiopulmonary by-pass and after the release of aortic cross clamp, about 10 minutes after the end of reperfusion.

A blood sample will be collected by peripheral vein and the sample sent by our laboratories to assess the concentration in µg/l of cardiac troponins Since arrival on intensive care unit and 6, 12, 24, 48 h after unclamping of the aorta.

Transesophageal echocardiographic study will be performed by two expert echocardiographers following the protocols of the Society of Cardiovascular Anesthesiologists and American Society of Echocardiography. Left ventricle myocardial performance index, LVEF (%), left ventricular regional wall motion, E/A ratio, E', E/E' and deceleration time (DT) of mitral inflow velocity will be measured; these measurements will be obteined.

Hemodynamic measurements will be obtained by an arterial and a pulmonary artery catheter (PAC) inserted before surgery, and will include arterial pressure (systolic, diastolic and mean pressure), pulmonary artery pressure (PAP), right atrial pressure (RAP), pulmonary artery wedge pressure (PAWP), cardiac output (CO) and cardiac index (CI), systemic vascular resistance (SVR), left ventricular stroke work (LVSW), left stroke volume variaton (LSVV) and coronary artery perfusion pressure (CPP).

New-onset atrial fibrillation, ventricular arrhythmia, low cardiac output syndrome (LCOS), inotropic support and/or intraaortic balloon pump >24 hours, myocardial infarction) and intensive care unit and hospital length of stay between two groups.

Temistocle Taccheri

MD, Resident in Anesthesia and Intensive Care Department

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Topotecan 3.5 mg/m^2 + Sorafenib dose escalation:

Topotecan 3.5 mg/m^2 + Sorafenib 400 mg po daily.

Topotecan 3.5 mg/m^2 + Sorafenib assigned dose level:
Sorafenib Dose level -1=200 mg po daily Sorafenib Dose level 1=400 mg po daily Sorafenib Dose level 2=400 mag po bid

Phase I

Phase II

Total

Sex: Female, Male

Race (NIH/OMB)

Region of Enrollment

ECOG: Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) from 0-5 that describes a patient's level of functioning where 0=Fully active, able to carry on all pre-disease performance without restriction and 5=Dead

Eastern Cooperative Onocology Group (ECOG) Perfomance Status

Origin of Cancer

Histology

Number of Prior Therapies

Response Evaluation Criteria in Solid Tumors (RECIST):
Measurable disease is defined by the presence of at least one measureable lesion. If the measureable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology.
Detectable disease is defined as a patient who does not have measureable disease, but has at least one: 1)CA-125 >= 2x ULN w/in 14d prior to registration 2)Ascites and/or pleural effusion attributed to tumor; 3)solid and/or cystic abnormalities on radiographic imaging that don't meet RECIST definitions for target lesions.

Response Evaluation

Platinum Sensitivity

CA125 at Enrollment

An initial 3 patients will be enrolled at dose level 1. If all 3 patients in dose level 1 complete the first cycle of therapy without a dose limiting toxicity (DLT), 3 patients will be enrolled at dose level 2. If 0 of 3 or 1 of 6 patients in dose level 2 experience a DLT, all subsequent patients will be enrolled in the Phase II cohort at dose level 2. If 2 of the first 3 or 2 of the total 6 patients experience DLT at dose level 2, then dose level 1 will be considered the MTD and used in the second phase.

Phase I Participants

Maximum Tolerated Dose (MTD)

To assess response in patients with recurrent or resistant epithelial ovarian cancer treated with Sorafenib plus Topotecan. Reponse evaluated per RECIST criteria where:
Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

Percentage of Participants With Response

To determine the progression-free survival of patients treated with Sorafenib plus Topotecan.

Topotecan 3.5 mg/m^2 + Sorafenib 400 mg po daily during phase II.
During phase I:
Topotecan 3.5 mg/m^2 + Sorafenib assigned dose level:
Sorafenib Dose level -1=200 mg po daily Sorafenib Dose level 1=400 mg po daily Sorafenib Dose level 2=400 mag po bid

Phase I & II

Progression-free Survival

To determine the rate of clinical benefit defined as the percentage of patients experiencing an objective response or a CA125 response.

Clinical Benefit

To determine duration of stable disease, in months

Duration of Stable Disease

Overall Study

Principal Investigator

Phase I/Phase II

Ovarian Cancer

Phase I: Dose Escalation, Phase II: MTD
Dose level -1: 200mg po daily Dose level 1: 400mg po daily (MTD) Dose level 2: 400mg po bid

Sorafenib

3.5mg/m2 weekly, 3 weeks on and one week off.

Topotecan

Medical & Surgical Specialists, LLC

Oncology Hematology Associates of SW Indiana

Fort Wayne Oncology & Hematology, Inc

Indiana University Simon Cancer Center

St. Vincent Hospital Cynecologic Oncology

Arnett Cancer Care

Medical Consultants, P.C.

Schwartz Gynecologic Oncology, PLLC

Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer

A Phase I/II Study of Sorafenib in Combination With Topotecan for the Treatment of Platinum-Resistant Recurrent Ovarian Cancer or Primary Peritoneal Carcinomatosis: Hoosier Oncology Group GYN06-111

antianginal/blödning

Ranolazine a Potential New Therapeutic Application

Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer

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