Gastric CancerPhase 1NCT01147991
Vaccine Therapy in Treating Patients With Epstein-Barr Virus-Related Cancer
A Phase 1 study testing EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine, laboratory biomarker analysis and pharmacological study in people with Gastric Cancer and Head and Neck Cancer, run by Cancer Research UK at 3 sites in United Kingdom.
Trial summary
RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with Epstein-Barr virus and cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Cancer, Head and Neck Cancer, Lymphoma
- What is being tested?
- EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine, laboratory biomarker analysis and pharmacological study
- Type of treatment
- Vaccines
- How many people
- 16 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Mar 2005to Apr 2011
- 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
DISEASE CHARACTERISTICS:
- Histologically confirmed malignancy of a type typically associated with Epstein-Barr virus (EBV) latent infection meeting the following criteria:
- The presence of EBV within the malignant cells has been demonstrated by immunohistochemistry for viral antigens or by EBER (EBV early RNA) in situ hybridization
- Patients in remission from disease or with disease for which no standard treatment is appropriate, as defined by 1 of the following groups:
- Have achieved a continuing complete response (CR) or unconfirmed CR
- Residual masses at the site of treated disease that are not progressing (i.e., stable disease) and for which no standard therapy is recognized
- Residual or recurrent disease that is low-volume and causing minimal or no symptoms and for which no standard therapy is recognized
- Completed standard therapy for malignancy ≥ 12 weeks before trial entry
- No more than 1 course of chemotherapy as treatment for EBV+ malignancy
- No ongoing toxic manifestations of prior treatment, except alopecia or certain grade 1 toxicities at the discretion of the investigator and Cancer Research UK
- No patients with active EBV+ cancer for whom evidence-based active treatment is available and likely to be offered to prolong life or relieve symptoms within 14 weeks of the first vaccination
PATIENT CHARACTERISTICS:
- WHO performance status 0 or 1
- Life expectancy ≥ 4 months
- Lymphocyte count must satisfy 1 of the following criteria:
- Greater than lower limit of the reference range in the investigator site
- Greater than or equal to 0.5 x 10^9/L AND recovery from nadir of lymphocyte numbers following primary treatment for EBV+ malignancy, judged by no successive rises in lymphocyte count measured up to 3 successive occasions 3 weeks apart
- Hemoglobin > 10.0 g/dL
- Absolute neutrophil count ≥ 1.5 x 10^9/L
- Platelet count ≥ 100 x 10^9/L
- Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Serum alkaline phosphatase < 1.5 times ULN
- ALT and/or AST < 1.5 times ULN
- Calculated creatinine clearance > 50 mL/min (uncorrected value) OR isotope clearance measurement > 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during study and for 6 months after completion of study treatment
- No known chronic active infection with hepatitis B, hepatitis C, or HIV
- No history of anaphylaxis or severe allergy to vaccinations
- No allergy to eggs or egg products
- No ongoing active infection
- No known splenic dysfunction
- No concurrent active autoimmune disease
- No prior NYHA class III or IV cardiac disease or concurrent congestive heart failure
- No concurrent active skin diseases requiring therapy (i.e., psoriasis, eczema)
- No other condition that, in the Investigator's opinion, would make the patient not a good candidate for this clinical trial
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior myeloablative therapy followed by an autologous or allogeneic hematopoietic stem cell transplant
- More than 12 weeks since prior and no concurrent chemotherapy or radiotherapy
- No splenectomy or splenic irradiation
- No concurrent immunosuppressive medication, including corticosteroids
- Long-term prophylactic use of inhaled corticosteroids allowed
- No major thoracic and/or abdominal surgery within the past 4 weeks from which the patient has not yet recovered
- No other concurrent anticancer or investigational drugs
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
University of Birmingham
Birmingham, England, B15 2TT
Royal Marsden - London
London, England, SW3 6JJ
Christie Hospital
Manchester, England, M20 4BX
About this study
Official title: A Phase I, Dose Escalation Trial of Recombinant Modified Vaccinia Ankara (MVA)-Based Vaccine Encoding Epstein-Barr Virus Target Antigens
RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with Epstein-Barr virus and cancer.
Read the detailed description
OBJECTIVES:
Primary
- To determine safety and to characterize the toxicity profile of EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine in patients in remission having been treated conventionally for Epstein-Barr virus (EBV) and malignancy.
- To describe changes in the frequency of functional T-cell responses to major histocompatibility complex (MHC) class I and II-restricted epitopes within EBNA1 and LMP2 in peripheral blood at sequential time-points before, during, and up to nine months after the vaccination course in these patients.
Secondary
- To assess changes in levels of EBV genome in plasma in these patients.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine intradermally on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for immune function, biomarker, and pharmacological studies.
After completion of study treatment, patients are followed up at weeks 11 and 14, and at 6 months and 1 year.
- Conditions
- Gastric Cancer, Head and Neck Cancer, Lymphoma, Lymphoproliferative Disorder, Nonneoplastic Condition
- Being tested
- EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine, laboratory biomarker analysis, pharmacological study
- Keywords
- Epstein-Barr virus infection, stage I nasopharyngeal cancer, stage II nasopharyngeal cancer, stage I adult Hodgkin lymphoma, stage II adult Hodgkin lymphoma, post-transplant lymphoproliferative disorder, stage I gastric cancer, stage II gastric cancer, adult nasal type extranodal NK/T-cell lymphoma, angioimmunoblastic T-cell lymphoma, stage I adult Burkitt lymphoma, contiguous stage II adult Burkitt lymphoma, contiguous stage II adult immunoblastic large cell lymphoma, stage I adult immunoblastic large cell lymphoma
- Medical subject headings
- Stomach Neoplasms, Head and Neck Neoplasms, Lymphoma, Lymphoproliferative Disorders, Epstein-Barr Virus Infections, Nasopharyngeal Neoplasms, Hodgkin Disease, Lymphoma, Extranodal NK-T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccineBiological
laboratory biomarker analysisOther
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of drug-related grade 3 or 4 systemic or local adverse events (defined using the NCI CTCAE version 3.0)
Occurrence of local skin reactions considered related to the vaccination
Occurrence of drug-related systemic reactions (e.g., transient fever)
Demonstration by ELIspot assays of the frequency of T-lymphocytes recognizing major histocompatibility complex (MHC) class I and II-restricted epitopes within EBNA1 and LMP2 in peripheral blood at sequential time-points before, during, and up to 9 mo ...
Secondary outcomes (1)
Measurement of EBV-genome levels in plasma
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2010 (estimated)
- Study startMar 2005
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastric 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
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cancer Research UK
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Neil M Stevens, MD, Principal investigator, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01147991
- Sponsor's protocol ID
- CDR0000675266
- Other IDs
- CRUK-PH1-101, EUDRACT-2004-001931-46
- Status last verified
- Feb 2012
- First submitted
- 18 Jun 2010
- Last updated
- 28 Feb 2012
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Dose Escalation Trial of Recombinant Modified Vaccinia Ankara (MVA)-Based Vaccine Encoding Epstein-Barr Virus Target Antigens
- ClinicalTrials.gov ID
- NCT01147991
- Acronym / sponsor ID
- CDR0000675266
- Conditions
- Gastric Cancer, Head and Neck Cancer, Lymphoma, Lymphoproliferative Disorder, Nonneoplastic Condition
- Keywords
- Epstein-Barr virus infection, stage I nasopharyngeal cancer, stage II nasopharyngeal cancer, stage I adult Hodgkin lymphoma, stage II adult Hodgkin lymphoma, post-transplant lymphoproliferative disorder, stage I gastric cancer, stage II gastric cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Cancer Research UKUniversity, hospital or other
- Study start
- Mar 2005
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 22 Jun 2010 (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.
RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with Epstein-Barr virus and cancer.
Detailed description
OBJECTIVES:
Primary
- To determine safety and to characterize the toxicity profile of EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine in patients in remission having been treated conventionally for Epstein-Barr virus (EBV) and malignancy.
- To describe changes in the frequency of functional T-cell responses to major histocompatibility complex (MHC) class I and II-restricted epitopes within EBNA1 and LMP2 in peripheral blood at sequential time-points before, during, and up to nine months after the vaccination course in these patients.
Secondary
- To assess changes in levels of EBV genome in plasma in these patients.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine intradermally on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for immune function, biomarker, and pharmacological studies.
After completion of study treatment, patients are followed up at weeks 11 and 14, and at 6 months and 1 year.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine | Biological | – |
| laboratory biomarker analysis | Other | – |
| pharmacological study | Other | – |
Primary outcome
Occurrence of drug-related grade 3 or 4 systemic or local adverse events (defined using the NCI CTCAE version 3.0)
Occurrence of local skin reactions considered related to the vaccination
Occurrence of drug-related systemic reactions (e.g., transient fever)
Demonstration by ELIspot assays of the frequency of T-lymphocytes recognizing major histocompatibility complex (MHC) class I and II-restricted epitopes within EBNA1 and LMP2 in peripheral blood at sequential time-points before, during, and up to 9 mo ...
1 secondary outcome
Measurement of EBV-genome levels in plasma
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 28 Feb 2012.
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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.
Neil M Stevens, MD principal investigator
University of Birmingham
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine, laboratory biomarker analysis and pharmacological study in people with Gastric Cancer and Head and Neck Cancer, run by Cancer Research UK at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 28 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. 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?
Occurrence of drug-related grade 3 or 4 systemic or local adverse events (defined using the NCI CTCAE version 3.0). The study lists 4 primary outcomes in all. 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 28 Feb 2012.