Atu027 Plus Gemcitabine in Advanced or Metastatic Pancreatic Cancer (Atu027-I-02)

Inclusion criteria

Lead-in safety period:

• Subjects between the age of 18 and 84 years
• Histologically or cytologically confirmed advanced or refractory cholangiocellular carcinoma, biliary tract cancer, non-small-cell lung carcinoma, duodenal cancer, soft tissue sarcoma, ovarian carcinoma, or another non-pancreatic cancer disease indicated for gemcitabine treatment as determined by the investigator
• Subjects who have previously received chemotherapy and standard curative or palliative care is not available, not effective, or unlikely to be effective
• No option for surgical resection or radiation in curative intent
• Eastern Cooperative Oncology Group (ECOG) performance status assessment of 0 to 2
• Life expectancy of at least 3 months
• No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
• Alanine aminotransferase (ALT) ≤3.0 x upper limit of normal (ULN; ≤5 x ULN for subjects with liver metastases)
• Aspartate aminotransferase (AST) ≤3.0 x ULN (≤5 x ULN for subjects with liver involvement with cancer)
• Total bilirubin ≤2.0 x ULN (liver metastasis <5 x ULN)
• Serum creatinine ≤1.5 x ULN
• Adequate bone marrow function: subjects should have an absolute granulocyte count of at least 1,500 (x 10e6/L) and platelet count of 100,000 (x 10e6/L) prior to the initiation of a cycle.
• Prothrombin time-international normalized ratio/partial thromboplastin time (PT-INR/PTT) <1.5 x ULN (subjects who are being therapeutically anti-coagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists). Low-dose aspirin is permitted (≤100 mg daily).
• Women of childbearing potential must have a negative urine pregnancy test at baseline.
• Women of childbearing potential and men must be willing to use highly effective contraceptive methods during the course of the study and 6 months after.
• Subjects must be willing and able (in the opinion of the investigator) to understand the subject information and informed consent form and to comply with the study protocol and procedures.
• Subjects must be willing and able to give written informed consent.

Main part:

• Subjects between the age of 18 and 84 years
• Subjects with locally advanced or metastatic pancreatic adenocarcinoma stage III/IV indicated for gemcitabine treatment as determined by the investigator
• No option for surgical resection or radiation in curative intent
• Histological or cytological documentation of non-hematologic, malignant solid tumor
• At least one measurable lesion or evaluable disease, as per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status assessment of 0 to 2
• Life expectancy of at least 3 months
• No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
• Alanine aminotransferase (ALT) <=3.0 x upper limit of normal (ULN; <=5 x ULN for subjects with liver metastases)
• Aspartate aminotransferase (AST) <=3.0 x ULN (<=5 x ULN for subjects with liver involvement with cancer)
• Total bilirubin <=2.0 x ULN (liver metastasis <=5 x ULN)
• Serum creatinine <=1.5 x ULN
• Adequate bone marrow function: subjects should have an absolute granulocyte count of at least 1,500 (x 10e6/L) and platelet count of 100,000 (x 10e6/L) prior to the initiation of a cycle.
• Prothrombin time-international normalized ratio/partial thromboplastin time (PT INR/PTT) <1.5 x ULN (subjects who are being therapeutically anti-coagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists). Low-dose aspirin is permitted (≤100 mg daily).
• Women of childbearing potential must have a negative urine pregnancy test at baseline.
• Women of childbearing potential and men must be willing to use highly effective contraceptive methods during the course of the study and 6 months after.
• Subjects must be willing and able (in the opinion of the investigator) to understand the subject information and informed consent form and to comply with the study protocol and procedures.
• Subjects must be willing and able to give written informed consent.

Exclusion criteria

Lead-in safety period:

• History of cardiac disease; congestive heart failure >New York Heart Association (NYHA) functional classification system Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset angina within 3 months prior to study entry or unstable angina, or ventricular cardiac arrhythmias requiring anti-arrhythmic therapy
• Poorly controlled diabetes defined as hemoglobin A1c (HbA1c) >=7%
• Poorly controlled hypertension, defined as systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg, despite optimal medical management
• Poorly controlled seizure disorder
• Subjects undergoing renal dialysis
• Known hypersensitivity to the study drugs or active substances or excipients of the preparations
• Pregnant or breast feeding
• Known hepatitis B or C or human immunodeficiency virus (HIV) infection (if documented in the subject's record
• Previous participation in this study
• Current or previous (within 30 days of enrolment) treatment with another investigational drug or participation in another clinical study.
• Subject is a relative of, or staff directly reporting to the investigator.
• Subject is an employee of the sponsor.
• Subject is committed under official or judicial order.
• Any other reason that the investigator considers makes the subject unsuitable to participate

Main part:

• History of cardiac disease; congestive heart failure >New York Heart Association (NYHA) functional classification system Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset angina within 3 months prior to study entry or unstable angina, or ventricular cardiac arrhythmias requiring anti-arrhythmic therapy
• Poorly controlled diabetes defined as hemoglobin A1c (HbA1c) >=8%
• Poorly controlled hypertension, defined as systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg, despite optimal medical management
• Poorly controlled seizure disorder
• Subjects undergoing renal dialysis
• Anticancer chemotherapy or immunotherapy during the study or before first study treatment. Subjects with recurrent disease after adjuvant treatment not progression-free for at least 6 months.
• Radiotherapy to target lesions during study or before study start
• Known hypersensitivity to the study drugs or active substances or excipients of the preparations
• Pregnant or breast feeding
• Known hepatitis B or C or human immunodeficiency virus (HIV) infection (if documented in the subject's record
• Previous participation in this study
• Current or previous (within 30 days of enrolment) treatment with another investigational drug or participation in another clinical study.
• Subject is a relative of, or staff directly reporting to the investigator.
• Subject is an employee of the sponsor.
• Subject is committed under official or judicial order.
• Any other reason that the investigator considers makes the subject unsuitable to participate