VXM01 Phase I Dose Escalation Study in Patients With Locally Advanced, Inoperable and Stage IV Pancreatic Cancer

Inclusion Criteria:

• Written informed consent, signed and dated
• Locally advanced, inoperable and stage IV pancreatic cancer patients according to UICC based on diagnostic imaging using computer-tomography (CT) or histological examinations
• Male or post-menopausal female
• Age above or equal to 18 years
• Chemotherapy naïve within 60 days before screening visit except gemcitabine treatment
• Karnovsky index >70
• Life expectancy >3 months
• Adequate renal, hepatic, and bone marrow function
• Absolute neutrophil count >1500/µL
• Hemoglobin >10 g/dL
• Platelets >75000/µL
• Prothrombin time and international normalized ratio (INR) <1.5 times upper limit of normal (ULN) (except under anticoagulant treatment)
• Aspartate aminotransferase <4 times ULN
• Alanine aminotransferase <4 times ULN
• Total bilirubin <3 times ULN
• Creatinine clearance estimated according to Cockcroft-Gault >30 mL/min
• Proteinuria <1 g protein on 24 h urine collection

Exclusion Criteria:

• State after pancreas resection (complete or partial)
• Resectable disease
• Drug trial participation within 60 days before screening visit
• Other previous or current malignancy except basal or squamous cell skin cancer, in situ cervical cancer, or any other cancer from which the patient has been disease-free for <2 years
• Prior vaccination with Ty21a

• Cardiovascular disease defined as:

  • Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg)
  • Arterial thromboembolic event within 6 months before randomization including:
  • Myocardial infarction
  • Unstable angina pectoris
  • Cerebrovascular accident
  • Transient ischemic attack
• Congestive heart failure New York Heart Association grade III to IV
• Serious ventricular arrhythmia requiring medication
• Clinically significant peripheral artery disease > grade 2b according to Fontaine
• Hemoptysis within 6 months before randomization
• Esophageal varices
• Upper or lower gastrointestinal bleeding within 6 months before randomization
• Significant traumatic injury within 4 weeks before randomization
• Non-healing wound, bone fracture or any history of gastrointestinal ulcers within three years before inclusion, or positive gastroscopy within 3 months before inclusion
• Gastrointestinal fistula
• Thrombolysis therapy within 4 weeks before randomization
• Bowel obstruction within the last 30 days before screening visit
• Liver cirrhosis ≥ grade B according to Child-Pugh Score-Classification
• Presence of any acute or chronic systemic infection
• Radiotherapy within 4 weeks before randomization
• Major surgical procedures, or open biopsy within 4 weeks before randomization
• Fine needle aspiration within 7 days before randomization

• Chronic concurrent therapy within 2 weeks before and during the double-blind study period with:

  • Corticosteroids (except steroids for adrenal failure) or immunosuppressive agents
  • Antibiotics
  • Bevacizumab
  • Any epidermal growth factor receptor inhibitor
  • Chemotherapy except gemcitabine before Day 10
• Multi-drug resistant gram-negative germ
• Pregnancy
• Lactation
• Inability to comply with study and/or follow-up procedures
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the study results or render the patient at high risk for treatment complications
• Women of childbearing potential
• Any history of drug hypersensitivity
• Any condition which results in an undue risk for the patient during the study participation according to the investigator