Pilot Phase 2 Study to Investigate the Preliminary Efficacy and Safety of INNO-206 in Advanced Pancreatic Cancer

• Disease Control Rate [ Time Frame: After all subjects have been on study for 4 months. ] [ Designated as safety issue: No ]
  Disease control rate is Complete Responders + Partial Responders + Stable Disease
• Progression-free Survival [ Time Frame: From the date of randomization until the date of first documented progression assessed up to 20 months. ] [ Designated as safety issue: No ]
  A >=20% increase in the sum of the LD of target lesions from the smallest sum of the LD recorded since the treatment started.
• Safety Assessments [ Time Frame: From randomization upto 15 months. ] [ Designated as safety issue: Yes ]
  Adverse events, serious adverse events, vital signs, physical examinations, ECG, safety labs will be evaluated for overall toxicity of INNO-206 in this population.

Patients with metastatic, locally advanced, or unresectable pancreatic ductal carcinomas (PDA) who have failed prior chemotherapy with gemcitabine regimens have an extremely poor prognosis with progression-free survival of around 13 weeks and median overall survival of approximately 20 weeks after second line chemotherapy. Recent studies suggest that albumin may be preferentially concentrated in pancreatic cancers that appear to be starved for this protein. Thus, any molecule attached to albumin would also collect inside the tumor. Based on its postulated mechanism of action, INNO-206 may improve the activity of doxorubicin without increasing its toxicity, as has been demonstrated in animal studies, and induce enhanced anti-tumor efficacy.

Inclusion Criteria:

• Age ≥ 18 years of age; male or female.
• Histologically or cytologically confirmed, locally advanced, unresectable, and/or metastatic pancreatic ductal adenocarcinoma.
• Cancer progression after treatment with one gemcitabine and one fluoropyrimidine-containing chemotherapy regimen.
• Capable of providing informed consent and complying with trial procedures.
• ECOG performance status 0-1.
• Life expectancy ≥ 8 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.)
• 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:

• Prior exposure to > 3 cycles or 225 mg/m2 of doxorubicin or Doxil®.
• Palliative surgery and/or radiation treatment less than 4 weeks prior to Randomization.
• Exposure to any investigational agent within 30 days of Randomization.
• Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit).
• 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 > 1.5x upper limit of normal (ULN), alanine aminotransferase (ALT) > 3×ULN or > 5×ULN if liver metastases are present, total bilirubin > 3×ULN, absolute neutrophil count < 1,500/mm3, platelet concentration < 100,000/mm3, absolute lymphocyte count < 1000/mm3, hematocrit level < 27% for females or < 30% for males, or coagulation tests (prothrombin time [PT], partial thromboplastin time [PTT], International Normalized Ratio [INR]) > 1.5×ULN, serum albumin ≤ 2.8 g/dL.
• Clinically evident congestive heart failure > class II of the New York Heart Association (NYHA) guidelines.
• Current, 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 ultrasound-determined, with absolute left ventricular ejection fraction (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 4 weeks prior to Randomization.
• 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.