VXM01 phase I dose escalation study in patients with locally advanced, inoperable and stage IV pancreatic cancer
| ISRCTN | ISRCTN68809279 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN68809279 |
| ClinicalTrials.gov number | NCT01486329 |
| Secondary identifying numbers | VXM01-01-DE |
- Submission date
- 05/12/2011
- Registration date
- 12/01/2012
- Last edited
- 21/01/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
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
Contact information
Dr Thomas Schmidt
Scientific
Scientific
Clinic of General Surgery
Im Neuenheimer Feld 105
University Clinics of Heidelberg
Heidelberg
69120
Germany
Study information
| Study design | Monocenter double-blind placebo-controlled phase I dose escalation study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Screening |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| 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 |
| Study acronym | VXM01-01-DE |
| Study objectives | 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(s) | Ethics committee of the Medical faculty of Heidelberg, 15/11/2011, ref: AFmu-283/2011 |
| Health condition(s) or problem(s) studied | 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 |
| 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 study start date | 06/12/2011 |
| Completion date | 01/12/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 72 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 06/12/2011 |
| Date of final enrolment | 01/12/2014 |
Locations
Countries of recruitment
- Germany
Study participating centre
Clinic of General Surgery
Heidelberg
69120
Germany
69120
Germany
Sponsor information
VAXIMM GmbH (Germany)
Industry
Industry
Julius-Hatry-Strasse 1
Mannheim
68163
Germany
| Website | http://www.vaximm.com |
|---|---|
"ROR" |
https://ror.org/03x5tah73 |
Funders
Funder type
Industry
VAXIMM GmbH (Germany)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 20/08/2012 | Yes | No | |
| Results article | results | 16/03/2015 | 21/01/2019 | Yes | No |
| Results article | results | 16/01/2018 | 21/01/2019 | Yes | No |
Editorial Notes
21/01/2019: pUblication references added
