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

A PHASE Ib/IIa STUDY OF COMBINATION THERAPY WITH GEMCITABINE AND ATU027 IN SUBJECTS WITH LOCALLY ADVANCED OR METASTATIC PANCREATIC ADENOCARCINOMA

The purpose of the study is to evaluate a new treatment strategy for advanced pancreatic cancer disease by combining the new investigational medicinal product Atu027 with the standard chemotherapeutic gemcitabine. This combination aims at enhancing gemcitabine´s anti-tumor activity with Atu027.

The objectives of this clinical trial are to evaluate safety and activity of two Atu027 schedules in combination with standard gemcitabine treatment in patients with advanced or metastatic pancreatic adenocarcinoma.

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