VXM01 Phase I Dose Escalation Study in Patients With Locally Advanced, Inoperable and Stage IV Pancreatic Cancer
Primary Purpose
Stage IV Pancreatic Cancer
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
VXM01
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Stage IV Pancreatic Cancer focused on measuring Pancreatic cancer, Cancer vaccine, Gemcitabine, Inoperable, Gemcitabine chemotherapy, Locally advanced
Eligibility Criteria
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
Sites / Locations
- Clinic of General Surgery
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
VXM01
Placebo
Arm Description
Investigational anti-angiogenic live cancer vaccine
Placebo control
Outcomes
Primary Outcome Measures
Safety and tolerability
Number of dose-limiting toxicities and maximum tolerated dose
Secondary Outcome Measures
Immune response
Number of immune positive patients
Tumor staging
Tumor staging according to RECIST criteria
Tumor perfusion
Tumor perfusion determined by DCE-MRI
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01486329
Brief Title
VXM01 Phase I Dose Escalation Study in Patients With Locally Advanced, Inoperable and Stage IV Pancreatic Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vaximm GmbH
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage IV Pancreatic Cancer
Keywords
Pancreatic cancer, Cancer vaccine, Gemcitabine, Inoperable, Gemcitabine chemotherapy, Locally advanced
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
72 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VXM01
Arm Type
Experimental
Arm Description
Investigational anti-angiogenic live cancer vaccine
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo control
Intervention Type
Biological
Intervention Name(s)
VXM01
Intervention Description
Live anti-angiogenic cancer vaccine drink solution, escalating dose
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Drink solution
Primary Outcome Measure Information:
Title
Safety and tolerability
Description
Number of dose-limiting toxicities and maximum tolerated dose
Time Frame
38 days
Secondary Outcome Measure Information:
Title
Immune response
Description
Number of immune positive patients
Time Frame
Up to 24 months
Title
Tumor staging
Description
Tumor staging according to RECIST criteria
Time Frame
Up to 24 months
Title
Tumor perfusion
Description
Tumor perfusion determined by DCE-MRI
Time Frame
Up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Schmidt, MD
Organizational Affiliation
University Clinics, Heidelberg
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinic of General Surgery
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
26459812
Citation
Wick W, Platten M, Wick A, Hertenstein A, Radbruch A, Bendszus M, Winkler F. Current status and future directions of anti-angiogenic therapy for gliomas. Neuro Oncol. 2016 Mar;18(3):315-28. doi: 10.1093/neuonc/nov180. Epub 2015 Oct 12.
Results Reference
derived
PubMed Identifier
22906006
Citation
Niethammer AG, Lubenau H, Mikus G, Knebel P, Hohmann N, Leowardi C, Beckhove P, Akhisaroglu M, Ge Y, Springer M, Grenacher L, Buchler MW, Koch M, Weitz J, Haefeli WE, Schmitz-Winnenthal FH. Double-blind, placebo-controlled first in human study to investigate an oral vaccine aimed to elicit an immune reaction against the VEGF-Receptor 2 in patients with stage IV and locally advanced pancreatic cancer. BMC Cancer. 2012 Aug 20;12:361. doi: 10.1186/1471-2407-12-361.
Results Reference
derived
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VXM01 Phase I Dose Escalation Study in Patients With Locally Advanced, Inoperable and Stage IV Pancreatic Cancer
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