Colorectal CancerPhase 1NCT02718430
VXM01 Phase I Study in Patients With Metastatic Colorectal Cancer With Liver Metastasis
A Phase 1 study testing VXM01 in people with Colorectal Cancer, run by Vaximm GmbH at 1 site in Germany.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- VXM01
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteGermany
- Study dates
- Feb 2016to Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent, including liver metastasis biopsy, signed and dated
- 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)
- Male or female patients who must be post-menopausal for at least 2 years or surgically sterile.
- Confirmed metastatic colorectal cancer (Stage IV)
- Presence of non-resectable liver metastasis
- Accessibility of liver metastasis appropriate for biopsy sampling
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- 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)
- 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
- Receipt of no more than 3 prior systemic therapy regimen for metastatic disease
- Measurable or non-measurable disease based on the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v. 1.1)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Life expectancy > 3 months
- Adequate renal, hepatic, and bone marrow function
- Leukocytes ≥4.0 x 109 / L
- Absolute neutrophil count (ANC) > 1,500/mm3
- Platelet count ≥ 100,000/mm3
- Hemoglobin ≥ 9 g/dL (can be post-transfusion)
- International normalized ratio (INR) ≤ 1.5
- Activated partial thromboplastin time (aPTT) ≤ 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- ALT and AST ≤ 2.5 times ULN
- Creatinine ≤ 2.0 mg/dL
- Proteinuria ≤ 1+ by urine dipstick OR ≤ 1 g by 24-hour urine collection
- 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
Who cannot join
- Concomitant treatment with anti-angiogenic therapy before progression of disease
- Treatment in any other clinical trial within 30 days before screening.
- Gastric bypass
- Ileostoma
- Other anatomical change of the gastrointestinal tract, interfering with gastrointestinal passage, except colostoma or colon bypass
- 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
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- Significant traumatic injury or surgery within the past 4 weeks
- Cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
- 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
- Pre-existing sensory or motor neuropathy ≥ grade 2
- History or evidence of CNS disease (e.g., uncontrolled seizures) by neurological examination unless adequately treated with standard medical therapy
- History or evidence of thrombotic or hemorrhagic disorders, including intracranial hemorrhage
- Uncontrolled hypertension (i.e., blood pressure > 160/100 mm Hg)
- 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
- Peripheral vascular disease ≥ grade 3 (i.e., symptomatic and interfering with activities of daily living requiring repair or revision)
- Positive for anti-typhoid IgG/IgM antibodies according to the onsite test on Day 0
- Hemoptysis within 6 months before randomization
- Esophageal varices
- Upper or lower gastrointestinal bleeding within 6 months before randomization
- 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
- Gastrointestinal fistula
- Thrombolysis therapy within 4 weeks before randomization
- Presence of any acute or chronic systemic infection
- Major surgical procedures, or open biopsy within 4 weeks before randomization
- 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
- Known multi-drug resistant gram-negative bacteria
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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
- Conditions
- Colorectal Cancer
- Being tested
- VXM01
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VXM01Drug
Oral immunotherapy targeting VEGFR2
| Study group | Role | What they receive |
|---|---|---|
| VXM01 | Experimental | VXM01 10E6 or 10E7 CFU Receives: Drug: VXM01 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability taking into account treatment-limiting toxicities (TLTs)
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.
Measured: 18 months
Secondary outcomes (6)
Immune Response by Enzme Linked Immuno Spot (ELISpot)
Patient-individual VEGFR-2 specific T-cell responses determined by ELISpot using cryopreserved peripheral blood mononuclear cells (PBMC)
Measured: 18 months
Immune biomarker by tumor tissue immunohistochemistry staining
Immune biomarker including T-cell infiltration, Treg, myeloid derived suppressor cells (MDSC) by tumor tissue immunohistochemistry staining
Measured: 66 days
Tumor vasculature by tumor tissue immunohistochemistry staining
Measured: 66 days
Serum biomarker Response by Enzyme Linked Immuno Sorbent Assay (ELISA)
Serum VEGF A and collagen IV measured by ELISA
Measured: 18 months
Clinical Response including tumor staging according to the response criteria in solid tumors (RECIST)
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.
Measured: 18 months
Biodistribution and shedding of VXM01
Bacterial vector tissue biodistribution, persistence, and shedding of viable Ty21a bacteria (VXM01) determined by cultivation of stool samples
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2016 (estimated)
- Study startFeb 2016
- Primary completionMar 2018
- Study completionMar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vaximm GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Carsten Gruellich, MD, Principal investigator, National Center of Tumor Diseases Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02718430
- Sponsor's protocol ID
- VXM01-03-DE
- Status last verified
- May 2018
- First submitted
- 16 Mar 2016
- Last updated
- 19 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02718430
- Acronym / sponsor ID
- VXM01-03-DE
- Conditions
- Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Vaximm GmbHIndustry (pharma, biotech, devices)
- Study start
- Feb 2016
- Primary completion
- Mar 2018 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 24 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| VXM01 | Experimental | Drug: VXM01VXM01 10E6 or 10E7 CFU |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Informed consent, including liver metastasis biopsy, signed and dated
- 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)
- Male or female patients who must be post-menopausal for at least 2 years or surgically sterile.
- Confirmed metastatic colorectal cancer (Stage IV)
- Presence of non-resectable liver metastasis
Key exclusion criteria (34 listed)
- Concomitant treatment with anti-angiogenic therapy before progression of disease
- Treatment in any other clinical trial within 30 days before screening.
- Gastric bypass
- Ileostoma
- Other anatomical change of the gastrointestinal tract, interfering with gastrointestinal passage, except colostoma or colon bypass
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VXM01Oral immunotherapy targeting VEGFR2 | Drug | VXM01 |
Primary outcome
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.
6 secondary outcomes
Immune Response by Enzme Linked Immuno Spot (ELISpot)
Time frame: 18 months
Immune biomarker by tumor tissue immunohistochemistry staining
Time frame: 66 days
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
Clinical Response including tumor staging according to the response criteria in solid tumors (RECIST)
Time frame: 18 months
Biodistribution and shedding of VXM01
Time frame: 10 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2018.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carsten Gruellich, MD principal investigator
National Center of Tumor Diseases Heidelberg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VXM01 in people with Colorectal Cancer, run by Vaximm GmbH at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability taking into account treatment-limiting toxicities (TLTs) (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2018.