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

Stage IV Pancreatic Cancer Clinical Trial

Official title:

VXM01 Phase I Dose Escalation Study in Patients With Locally Advanced, Inoperable and Stage IV Pancreatic Cancer to Examine Safety, Tolerability, and Immune Response to the Investigational VEGFR-2 DNA Vaccine VXM01

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01486329
• Other study ID #: VXM01-01-DE
• Status: Completed
• Phase: Phase 1
• First received: December 2, 2011
• Last updated: June 5, 2015
• Start date: December 2011
• Est. completion date: December 2014

Study information

• Verified date: June 2015
• Source: Vaximm GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial Summary

First-in-human phase I dose escalation study in patients with locally advanced, inoperable and stage IV pancreatic cancer to examine safety, tolerability, and immune response to the investigational VEGFR-2 DNA vaccine VXM01 to examine safety and tolerability, clinical and immunogenic response to the investigational vascular endothelial growth factor receptor 2 (VEGFR-2) DNA vaccine VXM01, and to define the maximum tolerated dose.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: December 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Neoplasms
• Stage IV Pancreatic Cancer

Intervention

Biological:
• VXM01
Live anti-angiogenic cancer vaccine drink solution, escalating dose
• Placebo
Drink solution

Locations

Country	Name	City	State
Germany	Clinic of General Surgery	Heidelberg

Sponsors (1)

Lead Sponsor	Collaborator
Vaximm GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability	Number of dose-limiting toxicities and maximum tolerated dose	38 days	Yes
Secondary	Immune response	Number of immune positive patients	Up to 24 months	No
Secondary	Tumor staging	Tumor staging according to RECIST criteria	Up to 24 months	No
Secondary	Tumor perfusion	Tumor perfusion determined by DCE-MRI	Up to 24 months	No