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VXM01 Phase I Study in Patients With Metastatic Colorectal Cancer With Liver Metastasis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02718430
Recruitment Status : Completed
First Posted : March 24, 2016
Last Update Posted : October 19, 2018
Sponsor:
Information provided by (Responsible Party):
Vaximm GmbH

Tracking Information
First Submitted Date  ICMJE March 16, 2016
First Posted Date  ICMJE March 24, 2016
Last Update Posted Date October 19, 2018
Study Start Date  ICMJE February 2016
Actual Primary Completion Date March 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2016)
Safety and tolerability taking into account treatment-limiting toxicities (TLTs) [ Time Frame: 18 months ]
AEs listed together with information on onset, duration, severity, seriousness, relationship to the study drug, relationship to chemotherapy and to the underlying disease, outcome, and action taken. Frequency tables by System Organ Class and preferred term.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2016)
  • Immune Response by Enzme Linked Immuno Spot (ELISpot) [ Time Frame: 18 months ]
    Patient-individual VEGFR-2 specific T-cell responses determined by ELISpot using cryopreserved peripheral blood mononuclear cells (PBMC)
  • Immune biomarker by tumor tissue immunohistochemistry staining [ Time Frame: 66 days ]
    Immune biomarker including T-cell infiltration, Treg, myeloid derived suppressor cells (MDSC) by tumor tissue immunohistochemistry staining
  • Tumor vasculature by tumor tissue immunohistochemistry staining [ Time Frame: 66 days ]
  • Serum biomarker Response by Enzyme Linked Immuno Sorbent Assay (ELISA) [ Time Frame: 18 months ]
    Serum VEGF A and collagen IV measured by ELISA
  • Clinical Response including tumor staging according to the response criteria in solid tumors (RECIST) [ Time Frame: 18 months ]
    Tumor staging according to the response criteria in solid tumors (RECIST) and investigation of the primary tumor and metastasis, e.g., determination of primary tumor size, number and size of metastasis.
  • Biodistribution and shedding of VXM01 [ Time Frame: 10 days ]
    Bacterial vector tissue biodistribution, persistence, and shedding of viable Ty21a bacteria (VXM01) determined by cultivation of stool samples
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE VXM01 Phase I Study in Patients With Metastatic Colorectal Cancer With Liver Metastasis
Official Title  ICMJE VXM01 Phase I Study in Patients With Metastatic Colorectal Cancer With Liver Metastasis Under Second or Third Line Therapy to Examine Safety, Efficacy, and Immune Biomarkers After Treatment With VXM01
Brief Summary Phase I study in patients with metastatic colorectal cancer with liver metastasis under second or third line therapy to examine safety, efficacy, and immune biomarkers after treatment with VXM01
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE Drug: VXM01
Oral immunotherapy targeting VEGFR2
Study Arms  ICMJE Experimental: VXM01
VXM01 10E6 or 10E7 CFU
Intervention: Drug: VXM01
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 28, 2017)
6
Original Estimated Enrollment  ICMJE
 (submitted: March 18, 2016)
24
Actual Study Completion Date  ICMJE March 2018
Actual Primary Completion Date March 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Informed consent, including liver metastasis biopsy, signed and dated
  2. Histologically or cytologically confirmed colorectal cancer, excluding primary tumors of appendiceal origin (participants are eligible to enroll irrespective of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status)
  3. Male or female patients who must be post-menopausal for at least 2 years or surgically sterile.
  4. Confirmed metastatic colorectal cancer (Stage IV)
  5. Presence of non-resectable liver metastasis

    • Accessibility of liver metastasis appropriate for biopsy sampling
    • Adequate coagulation parameters including platelet count ≥100,000/mm3
    • Absence of concomitant medication which could represent a contraindication for biopsy (e.g., anti-platelet drugs including aspirin, ticlopidine, clopidogrel, IIb/IIIa receptor antagonists, non-steroidal anti-inflammatory drugs [NSAIDs], and vitamin K antagonist anticoagulants)
  6. The participant has received first-line irinotecan- or oxaliplatin-based therapy without or in combination with a targeted antibody for metastatic disease and a) Experienced radiographic disease progression during first-line therapy, or b) Experienced radiographic disease progression ≤ 6 months after the last dose of first-line therapy, or c) Discontinued part or all of first-line therapy due to toxicity and experienced radiographic disease progression ≤ 6 months after the last dose of first-line therapy
  7. Receipt of no more than 3 prior systemic therapy regimen for metastatic disease
  8. Measurable or non-measurable disease based on the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v. 1.1)
  9. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  10. Life expectancy > 3 months
  11. Adequate renal, hepatic, and bone marrow function
  12. Leukocytes ≥4.0 x 109 / L
  13. Absolute neutrophil count (ANC) > 1,500/mm3
  14. Platelet count ≥ 100,000/mm3
  15. Hemoglobin ≥ 9 g/dL (can be post-transfusion)
  16. International normalized ratio (INR) ≤ 1.5
  17. Activated partial thromboplastin time (aPTT) ≤ 1.5 times upper limit of normal (ULN)
  18. Bilirubin ≤ 1.5 times ULN
  19. ALT and AST ≤ 2.5 times ULN
  20. Creatinine ≤ 2.0 mg/dL
  21. Proteinuria ≤ 1+ by urine dipstick OR ≤ 1 g by 24-hour urine collection
  22. Patients who are able to understand the nature and purpose of the study including possible risks, willing to comply with the requirements, and to provide their written informed consent to participate in the study

Exclusion Criteria:

  1. Concomitant treatment with anti-angiogenic therapy before progression of disease
  2. Treatment in any other clinical trial within 30 days before screening.
  3. Gastric bypass
  4. Ileostoma
  5. Other anatomical change of the gastrointestinal tract, interfering with gastrointestinal passage, except colostoma or colon bypass
  6. Untreated CNS metastases. Participants with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation ending at least 2 weeks prior to randomization, or after surgical resection performed at least 28 days prior to randomization. No evidence of Grade greater than or equal to 1 CNS hemorrhage based on pretreatment Magnetic Resonance Imaging (MRI) or intravenous (IV) contrast CT scan
  7. Significant traumatic injury or surgery within the past 4 weeks
  8. Cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
  9. Other malignancies within the past 5 years except for adequately treated carcinoma in situ of the cervix, and/or basal cell skin cancer, and/or early endometrial carcinoma
  10. Pre-existing sensory or motor neuropathy ≥ grade 2
  11. History or evidence of CNS disease (e.g., uncontrolled seizures) by neurological examination unless adequately treated with standard medical therapy
  12. History or evidence of thrombotic or hemorrhagic disorders, including intracranial hemorrhage
  13. Uncontrolled hypertension (i.e., blood pressure > 160/100 mm Hg)
  14. Clinically significant cardiovascular disease, including any of the following:

    • Myocardial infarction or unstable angina within the past 6 months
    • New York Heart Association class III-IV congestive heart failure
    • Poorly controlled cardiac arrhythmia despite medication, except rate controlled atrial fibrillation
  15. Peripheral vascular disease ≥ grade 3 (i.e., symptomatic and interfering with activities of daily living requiring repair or revision)
  16. Positive for anti-typhoid IgG/IgM antibodies according to the onsite test on Day 0
  17. Hemoptysis within 6 months before randomization
  18. Esophageal varices
  19. Upper or lower gastrointestinal bleeding within 6 months before randomization
  20. Non-healing wound, incomplete wound healing, bone fracture or any history of gastrointestinal ulcers within three years before inclusion, or positive gastroscopy within 3 months before inclusion
  21. Gastrointestinal fistula
  22. Thrombolysis therapy within 4 weeks before randomization
  23. Presence of any acute or chronic systemic infection
  24. Major surgical procedures, or open biopsy within 4 weeks before randomization
  25. Chronic concurrent therapy within 2 weeks before and during the initial treatment period (Day 1 to Day 7):

    • Corticosteroids (except steroids for adrenal failure or emesis prophylaxis up to 4 mg daily dose) or immunosuppressive agents
    • Antibiotics
    • Bevacizumab or any other anti-angiogenic treatment
  26. Known multi-drug resistant gram-negative bacteria
  27. 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
  28. Women of childbearing potential
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02718430
Other Study ID Numbers  ICMJE VXM01-03-DE
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Vaximm GmbH
Study Sponsor  ICMJE Vaximm GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Carsten Gruellich, MD National Center of Tumor Diseases Heidelberg
PRS Account Vaximm GmbH
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP