Safety and Maximum Tolerated Dose (MTD) Study of INNO-206 in Subjects With Advanced Solid Tumors

An Open-Label Phase 1 Study to Investigate the Safety and Maximum Tolerated Dose of INNO-206 (Doxorubicin-6-Maleimidocaproyl Hydrazone; DOXO-EMCH) Administered as a 30 Minute Infusion Every 3 Weeks in Subjects With Advanced Solid Tumors

This is a phase 1b open-label study evaluating the preliminary safety and maximum tolerated dose of a new formulation of INNO-206 administered at doses of 230 mg/m2, 350 mg/m2 and 450 mg/m2 (165, 260, 325 mg/m2 doxorubicin equivalents, respectively) through intravenous infusion on Day 1 every 21 days for up to 6 cycles.

Inclusion Criteria:

• Age between 18 and 70 years, male or female.
• Histologically or cytologically confirmed malignant solid tumor that has relapsed or is refractory to standard therapy.
• Subjects who have received prior radiation therapy with stable CNS metastasis with no progression of brain metastasis by CT/MRI scan in last 4 weeks.
• Capable of providing informed consent and complying with trial procedures.
• ECOG performance status 0-2.
• Life expectancy >12 weeks.
• Measurable or evaluable disease according to RECIST 1.1 criteria.
• 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.
• 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.

Exclusion Criteria:

• Palliative surgery, chemotherapy, immunotherapy and/or radiation less than 4 weeks prior to the Screening Visit.
• Exposure to any investigational agent within 30 days of the Screening Visit.
• Laboratory values: Screening serum creatinine greater than or equal to 1.5 mg/dL, alanine aminotransferase (ALT) greater than 3 times the upper limit of normal, total bilirubin greater than 3 times the upper limit of normal, white blood cell (WBC) count < 3500/mm3, absolute neutrophil count < 2000/mm3, platelet concentration < 100,000/mm3, hematocrit level < 33% for females or < 35% for males, or coagulation tests (PT,PTT) >1.5 times the upper limit or normal.
• Clinically evident congestive heart failure > class II of the New York Heart Association (NYHA) guidelines.
• 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.
• Serious myocardial dysfunction defined scintigraphically (MUGA, myocardial scintigram)or ultrasound determined absolute left ventricular ejection fraction (LVEF) < 45% of predicted.
• History of HIV infection.
• Active, clinically significant serious infection requiring treatment with antibiotics, antivirals or antifungals.
• Major surgery within 3 weeks prior to treatment.
• Substance abuse or any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
• Any condition that is unstable and could jeopardize the subject's participation in the study.