Plain English Summary
Background and study aims
The aim of the study is to test the safety and tolerability of VXM01, a novel anti-angiogenic cancer vaccine which targets the blood vessels of solid tumors. Signs of immunological and clinical response will also be monitored. This study is the first human clinical trial with VXM01. A mouse-analog vaccine has shown promising activity and a good safety profile in test animals. VXM01 is administered in ascending doses following a step-wise approach.
Who can participate?
Locally advanced, inoperable and metastatic pancreatic cancer patients of aged 18 or over.
What does the study involve?
All patients receive standard-of-care chemotherapy and are randomly allocated to receive either VXM01 or placebo (dummy).
What are the possible benefits and risks of participating?
Not provided.
Where is the study run from?
University Hospital in Heidelberg, Germany.
When is study starting and how long is it expected to run for?
The study starts in December 2011, and patients will be followed up for a maximum period of 24 months.
Who is funding the study?
VAXIMM GmbH, Mannheim, Germany.
Who is the main contact?
Dr Thomas Schmidt
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT01486329
Protocol/serial number
VXM01-01-DE
Study information
Scientific 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: First-in-human, monocenter, double-blind, placebo-controlled, phase I dose escalation study
Acronym
VXM01-01-DE
Study hypothesis
The aim of the study is to test the safety and tolerability of VXM01, a novel anti-angiogenic cancer vaccine which targets the blood vessels of solid tumors. Signs of immunological and clinical response will also be monitored. This study is the first human clinical trial with VXM01. A mouse-analog vaccine has shown promising activity and a good safety profile in test animals. This study is conducted in a single center at the University Hospital in Heidelberg, Germany.
On 05/02/2014 the following changes were made to the trial record:
1. The anticipated end date was changed from 31/03/2013 to 01/12/2014
2. The target number of participants was changed from 37 to 72
Ethics approval
Ethics committee of the Medical faculty of Heidelberg, 15/11/2011, ref: AFmu-283/2011
Study design
Monocenter double-blind placebo-controlled phase I dose escalation study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Screening
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Locally advanced, inoperable and stage IV pancreatic cancer
Intervention
1. VXM01, live anti-angiogenic cancer vaccine, escalating doses
2. Placebo drink solution
Intervention type
Other
Phase
Phase I
Drug names
Primary outcome measure
Safety and tolerability: number of dose-limiting toxicities and maximum tolerated dose at day 38
Secondary outcome measures
1. Immune response: number of positive patients
2. Clinical response: tumor staging according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria
3. Tumor perfusion: tumor perfusion determined by dynamic contrast enhanced-magnetic
resonance imaging (DCE-MRI)
Measured upto 24 months
Overall trial start date
06/12/2011
Overall trial end date
01/12/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Written informed consent, signed and dated
2. Locally advanced, inoperable and stage IV pancreatic cancer patients according to Union for International Cancer Control (UICC) based on diagnostic imaging using computer-tomography (CT) or histological examinations
3. Male or post-menopausal female
4. Age more than or equal to 18 years
5. Chemotherapy naive within 60 days before screening visit except gemcitabine treatment
6. Karnovsky index >70
7. Life expectancy > 3 months
8. Adequate renal, hepatic, and bone marrow function
9. Absolute neutrophil count >1500/µL
10. Hemoglobin >10 g/dL
11. Platelets >75000/µL
12. Prothrombin time and international normalized ratio (INR) <1.5 times upper limit of normal (ULN) (except under anticoagulant treatment)
13. Aspartate aminotransferase <4 times ULN
14. Alanine aminotransferase <4 times ULN
15. Total bilirubin <3 times ULN
16. Creatinine clearance estimated according to Cockcroft-Gault >30 mL/min
17. Proteinuria <1 g protein on 24 h urine collection
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
72
Participant exclusion criteria
1. State after pancreas resection (complete or partial)
2. Resectable disease
3. Drug trial participation within 60 days before screening visit
4. 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
5. Prior vaccination with Ty21a
6. Cardiovascular disease defined as:
6.1. Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg)
6.2. Arterial thromboembolic event within 6 months before randomization including:
6.2.1. Myocardial infarction
6.2.2. Unstable angina pectoris
6.2.3. Cerebrovascular accident
6.2.4 Transient ischemic attack
7. Congestive heart failure New York Heart Association grade III to IV
8. Serious ventricular arrhythmia requiring medication
9. Clinically significant peripheral artery disease > grade 2b according to Fontaine
10. Hemoptysis within 6 months before randomization
11. Esophageal varices
12. Upper or lower gastrointestinal bleeding within 6 months before randomization
13. Significant traumatic injury within 4 weeks before randomization
14. Non-healing wound, bone fracture or any history of gastrointestinal ulcers within three years before inclusion, or positive gastroscopy within 3 months before inclusion
15. Gastrointestinal fistula
16. Thrombolysis therapy within 4 weeks before randomization
17. Bowel obstruction within the last 30 days before screening visit
18. Liver cirrhosis ≥ grade B according to Child-Pugh Score-Classification
19. Presence of any acute or chronic systemic infection
20. Radiotherapy within 4 weeks before randomization
21. Major surgical procedures, or open biopsy within 4 weeks before randomization
22. Fine needle aspiration within 7 days before randomization
23. Chronic concurrent therapy within 2 weeks before and during the double-blind study period with:
23.1. Corticosteroids (except steroids for adrenal failure) or immunosuppressive agents
23.2. Antibiotics
23.3. Bevacizumab
23.4. Any epidermal growth factor receptor inhibitor
23.5. Chemotherapy except gemcitabine before day 10
24. Multi-drug resistant gram-negative germ
25. Pregnancy
26. Lactation
27. Inability to comply with study and/or follow-up procedures
28. 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
29. Women of childbearing potential
30. Any history of drug hypersensitivity
31. Any condition which results in an undue risk for the patient during the study participation according to the investigator
Recruitment start date
06/12/2011
Recruitment end date
01/12/2014
Locations
Countries of recruitment
Germany
Trial participating centre
Clinic of General Surgery
Heidelberg
69120
Germany
Sponsor information
Organisation
VAXIMM GmbH (Germany)
Sponsor details
Julius-Hatry-Strasse 1
Mannheim
68163
Germany
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
VAXIMM GmbH (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2012 protocol in http://www.ncbi.nlm.nih.gov/pubmed/22906006
Publication citations
-
Protocol
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, 12, 361, doi: 10.1186/1471-2407-12-361.