Study to Investigate the Safety and Activity of Aldoxorubicin Plus Gemcitabine in Subjects With Metastatic Solid Tumors

An open-label Phase 1b study to investigate the preliminary safety and activity of aldoxorubicin plus gemcitabine in subjects with metastatic solid tumors administered at doses of 170, 250 or 350 mg/m2 by intravenous infusion (IVI) on Day 1 every 21 days plus 900 mg/m2 gemcitabine on Days 1 and 8 every 21 days.

Inclusion criteria

• Age between 15-80 years, male or female.
• Advanced, unresectable, metastatic solid tumor that has either relapsed or was refractory to treatment with at least 1 prior chemotherapy or immunotherapy regimen and for which no standard approved therapy exists.
• Progressive disease (PD) < 6 months prior to enrollment.
• Capable of providing informed consent and complying with trial procedures.
• ECOG PS 0-2 (Appendix B).
• Life expectancy >12 weeks.
• Measurable tumor lesions according to RECIST 1.1 criteria.
• Women must not be able to become pregnant (eg 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.)
• Males and their female partner(s) of child-bearing potential must use 2 forms of effective contraception (see Inclusion 8 plus condom or vasectomy for males) from the last menstrual period of the female partner during the study treatment and for 6 months after the final dose of study treatment.
• 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 the subject will be able to keep all study-related appointments.

Exclusion criteria

• Prior exposure to >5 cycles or 375 mg/m2 of either doxorubicin or Doxil®.
• Chemotherapy, palliative surgery and/or radiation treatment less than 30 days prior to enrollment.
• Exposure to any investigational agent within 30 days of enrollment.
• CNS metastases that are symptomatic.
• History of other malignancies except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix unless documented free of cancer for ≥5 years.
• Laboratory values: Screening serum creatinine >1.5×ULN, ALT >3×ULN, or >5×ULN if liver metastases are present, total bilirubin >3×ULN, ANC <1,500/mm3, platelet concentration <100,000/mm3, hematocrit level <25% for females or <27% for males, coagulation tests (PT, PTT, INR) >1.5×ULN, and albumin <2.0 g/dL.
• Clinically evident CHF > class II of the NYHA guidelines (Appendix D).
• Current serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V (Appendix F).
• 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 QT prolongation is not allowed (Appendix G).
• History or signs of active coronary artery disease with or without angina pectoris.
• Serious myocardial dysfunction defined scintigraphically (eg MUGA, myocardial scintigram) or ultrasound determined absolute LVEF <45% of predicted.
• History of HIV infection.
• Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.
• Major surgery within 21 days prior to enrollment.
• 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.