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
1. Age ≥ 18 years, male or female.
2. Histologically or cytologically confirmed malignant solid tumor that has relapsed or
is refractory to standard therapy or no standard chemotherapy exists.
3. Capable of providing informed consent and complying with trial procedures.
4. Baseline absolute left ventricular ejection fraction (LVEF) measured
scintigraphically (MUGA, myocardial scintigram) or by ultrasound (echocardiogram) ≥
Institutional Lower Limit of Normal.
5. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2.
6. Life expectancy > 12 weeks.
7. Measurable or evaluable disease according to RECIST 1.1 criteria.15
8. 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.]
9. Women of child bearing potential must have a negative serum or urine pregnancy test
at the Screening Visit and be non-lactating.
10. Geographic accessibility to the site that ensures that the subject will be able to
keep all study-related appointments.
1. Palliative surgery, chemotherapy, immunotherapy and/or radiation treatment < 4 weeks
prior to the Screening Visit.
2. Prior treatment with ≥ 150 mg/m2 doxorubicin HCl or Doxil® cumulative dose, or
epirubicin ≥ 150 mg/m2.
3. Exposure to any investigational agent within 30 days of Randomization.
4. Evidence of active or uncontrolled central nervous system (CNS) metastasis (negative
imaging study performed due to suspicion of CNS metastasis within 4 weeks of
5. History of other malignancies except cured basal cell carcinoma, squamous cell
carcinoma, superficial bladder cancer or carcinoma in situ of the cervix.
6. 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.
7. Clinically evident congestive heart failure (CHF) > class II of the New York Heart
Association (NYHA) guidelines.
8. 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.
9. Serious clinically significant cardiac arrhythmias, defined as the existence of an
absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
10. History or signs of active coronary artery disease with or without angina pectoris.