Phase 1b Study to Investigate the Safety and Maximum Tolerated Dose of Aldoxorubicin (INNO-206) Plus Doxorubicin HCL in Subjects With Advanced Solid Tumors

An Open-Label Phase 1b Study to Investigate the Safety and Maximum Tolerated Dose of Aldoxorubicin (INNO-206) Plus Doxorubicin HCl Administered as Infusions Every 3 Weeks in Subjects with Advanced Solid Tumors

Inclusion criteria

• Age ≥ 18 years, male or female.
• Histologically or cytologically confirmed malignant solid tumor that has relapsed or is refractory to standard therapy or no standard chemotherapy exists.
• Capable of providing informed consent and complying with trial procedures.
• Baseline absolute left ventricular ejection fraction (LVEF) measured scintigraphically (MUGA, myocardial scintigram) or by ultrasound (echocardiogram) ≥ Institutional Lower Limit of Normal.
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2.
• Life expectancy > 12 weeks.
• Measurable or evaluable disease according to RECIST 1.1 criteria.15
• Women must not be able to become pregnant (e.g., post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. [Adequate contraception includes: oral contraception, implanted contraception, intrauterine device implanted for at least 3 months, or barrier method in conjunction with spermicide.]
• Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
• Geographic accessibility to the site that ensures that the subject will be able to keep all study-related appointments.

Exclusion criteria

• Palliative surgery, chemotherapy, immunotherapy and/or radiation treatment < 4 weeks prior to the Screening Visit.
• Prior treatment with ≥ 150 mg/m2 doxorubicin HCl or Doxil® cumulative dose, or epirubicin ≥ 150 mg/m2.
• Exposure to any investigational agent within 30 days of Randomization.
• Evidence of active or uncontrolled central nervous system (CNS) metastasis (negative imaging study performed due to suspicion of CNS metastasis within 4 weeks of Screening Visit).
• History of other malignancies except cured basal cell carcinoma, squamous cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix.
• Laboratory values: Screening serum creatinine ≥ 2 times the upper limit of normal (ULN), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the ULN if no liver metastases or 5 times the ULN if liver metastases, total bilirubin > 2 times the ULN, white blood cell (WBC) count < 3500/mm3, or absolute neutrophil count (ANC) < 1500/mm3, platelet concentration < 100,000/mm3, hematocrit level < 25% for females or < 27% for males, or coagulation tests (prothrombin time [PT]; partial thromboplastin time [PTT]), International Normalized Ration (INR) > 1.5 times the ULN, serum albumin < 2.0g/dL.
• Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association (NYHA) guidelines.
• Baseline QTc > 470 msec and/or previous history of QT prolongation while taking other medications. Concomitant use of medications associated with a high incidence of QTc prolongation is not allowed.
• Serious clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
• History or signs of active coronary artery disease with or without angina pectoris.