A Phase I Study to Assess the Safety, Pharmacokinetics, and Potential Effects of Amrubicin on the QT/QTc Interval in Cancer Patients With Advanced Solid Tumors.

Exclusion Criteria

• •Patients meeting any of the following criteria will be excluded from the study:
• •1. Hypersensitivity to amrubicin or related compounds;
• •2. Radiotherapy with curative intent to a primary disease complex ≤ 28 days before first dose; cranial radiotherapy ≤ 21 days before first dose; radiotherapy to all other areas ≤ 7 days before first dose of amrubicin;
• •3. History or presence of clinically significant abnormal 12-lead ECG or triplicate ECGs with a mean QT interval corrected for heart rate (HR) using Fridericia's method (QTcF) of \>450 msec (males) or \>470 msec (females), a PR interval \>240 msec or a QRS interval \>110 msec (within 3 months of screening visit);
• •4. Left ventricular ejection fraction (LVEF) \<50%;
• •5. Recent history (within 3 months of screening visit) of pericarditis and pericardial effusion;
• •6. History within 6 months of the screening visit of one of the following:
• •* cardiac disease including congenital long-QT syndrome,
• •* angina, congestive heart failure,
• •* myocardial ischemia or infarction,
• •* myocarditis, chest pain or dyspnea on exertion of cardiac origin,,
• •* idiopathic or hypertrophic cardiomyopathy,
• •* sarcoidosis,
• •* syncope,
• •* epilepsy,
• •* or other clinically significant cardiac disease;
• •7. Family history of long QT syndrome;
• •8. Use of implantable pacemaker or implantable cardioverter defibrillator;
• •9. Clinically significant bradycardia (\<50 beats per minute);
• •10. Systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg;
• •11. Previous treatment with an investigational agent or any anticancer therapy within 4 weeks prior to the 'off-drug' visit;
• •12. Previous treatment with anticancer therapy and has not fully recovered (Common Terminology Criteria Adverse Event \[CTCAE\] Grade 1, except alopecia) from the toxic effects of that treatment;
• •13. Treatment with any medication known to produce QT prolongation enzyme-inducing anticonvulsants, non-prescription medications including topical medications, all vitamins, minerals, herbs or dietary supplements/remedies (e.g., Saint John's Wort or Milk Thistle) for at least 7 days before the start of the off-drug visit;
• •14. Previous treatment with any anthracycline;
• •15. Any condition that would put the patient at undue risk or discomfort as a result of adherence to study procedures;
• •16. Women who are pregnant or nursing;
• •17. Uncontrolled intercurrent illness such as myelosuppression, renal impairment, hepatic impairment, infection and uncontrolled diabetes;
• •18. Symptomatic central nervous system metastases. Patients with asymptomatic brain metastases are allowed. The patient must be stable for ≥ 2 weeks after radiotherapy, if the patient is on corticosteroids, the dose of corticosteroids must have been stable for ≥ 2 weeks prior to the first dose of study treatment, or be in the process of being tapered;
• •19. Suspected, diffuse idiopathic interstitial lung disease or pulmonary fibrosis not related to prior treatment;
• •20. History of seropositive HIV or patients who are receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications;
• •21. Positive urine drug screen for undeclared concomitant medications and/or illegal drug use at screening.