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

• ClinicalTrials.gov Identifier: NCT01486329
• Recruitment Status: Completed
• First Posted: December 6, 2011
• Last Update Posted: June 8, 2015
• Sponsor: Vaximm GmbH
• Information provided by (Responsible Party): Vaximm GmbH

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.

Condition or disease	Intervention/treatment	Phase
Stage IV Pancreatic Cancer	Biological: VXM01; Biological: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: December 2011
• Actual Primary Completion Date: October 2014
• Actual Study Completion Date: December 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: VXM01; Investigational anti-angiogenic live cancer vaccine	Biological: VXM01; Live anti-angiogenic cancer vaccine drink solution, escalating dose
Placebo Comparator: Placebo; Placebo control	Biological: Placebo; Drink solution

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability [ Time Frame: 38 days ]
   Number of dose-limiting toxicities and maximum tolerated dose

Secondary Outcome Measures :

1. Immune response [ Time Frame: Up to 24 months ]
   Number of immune positive patients
2. Tumor staging [ Time Frame: Up to 24 months ]
   Tumor staging according to RECIST criteria
3. Tumor perfusion [ Time Frame: Up to 24 months ]
   Tumor perfusion determined by DCE-MRI

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Germany

Clinic of General Surgery

Heidelberg, Germany, 69120

Sponsors and Collaborators

Vaximm GmbH

Investigators

• Principal Investigator: Thomas Schmidt, MD; University Clinics, Heidelberg

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Vaximm GmbH
• ClinicalTrials.gov Identifier: NCT01486329
• Other Study ID Numbers: VXM01-01-DE
• First Posted: December 6, 2011
• Last Update Posted: June 8, 2015
• Last Verified: June 2015

Keywords provided by Vaximm GmbH:

Pancreatic cancer; Cancer vaccine; Gemcitabine; Inoperable; Gemcitabine chemotherapy; Locally advanced

Additional relevant MeSH terms:

Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases