A Phase Ib Trial of MVA-EBNA1/LMP2 Vaccine in Nasopharyngeal Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Cancer Research UK
Sponsor:
Information provided by (Responsible Party):
Cancer Research UK
ClinicalTrials.gov Identifier:
NCT01800071
First received: February 25, 2013
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

This clinical study is looking at a vaccine called MVA-EBNA1/LMP2. This is a new vaccine that has already been studied in small number of cancer patients.

The vaccine is designed to boost a patient's immunity against a common virus. The virus is called Epstein Barr virus or EBV. EBV is sometimes found inside cancer cells and is commonly found in nasopharyngeal cancer cells.


Condition Intervention Phase
Nasopharyngeal Cancer
Epstein Barr Virus Infections
Drug: MVA-EBNA1/LMP2 vaccine
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Cancer Research UK (CR-UK) Phase Ib Trial to Determine the Safety, Tolerability and Immunogenicity of Extended Schedule Vaccination With MVA-EBNA1/LMP2 in Patients With Epstein Barr Virus Positive (EBV+) Nasopharyngeal Carcinoma (NPC).

Resource links provided by NLM:


Further study details as provided by Cancer Research UK:

Primary Outcome Measures:
  • Immune response to three cycles of MVA-EBNA1/LMP2 vaccine [ Time Frame: pre-vaccination to 4 weeks post third vaccine ] [ Designated as safety issue: No ]
    To be determined by ex vivo ELIspot assays quantifying EBV EBNA1 and LMP2-specific effectors in samples before vaccination, during the three cycle vaccine course and within 4 weeks after the third vaccine cycle.

  • Occurrence of adverse events defined according to NCI CTCAE version 4.02 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immune memory and recall response to MVA-EBNA1/LMP2 vaccination [ Time Frame: pre and post vaccines one and four. ] [ Designated as safety issue: No ]
    To be determined by ex vivo ELIspot assays quantifying EBV EBNA1 and LMP2-specific effectors in samples before and within 4 weeks after the first and fourth vaccine cycles

  • Measurement of EBV genome levels in plasma before, during and after vaccination [ Time Frame: pre- vaccination to 12 months post vaccination ] [ Designated as safety issue: No ]
  • Tumour response as determined by Immune-Related Response Criteria (irRC) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: March 2013
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Detailed Description:

The main aims of the clinical study are to find out more about how the immune system responds to the vaccine, more about the potential side effects of the vaccine and the effects of giving an additional booster vaccination on the immune system.

Approximately 18 patients with EBV positive nasopharyngeal cancer (NPC) will be recruited to the trial. Patients will receive up to four vaccinations with the MVA-EBNA1/LMP2 vaccine. The first three vaccines will be given at 3 weekly intervals, followed by a fourth vaccine 12 weeks later. The vaccine will be given by intradermal injection with the dose divided across multiple injection sites on the arm, or on the thigh.

Patients will participate in the study for approximately 12 months from first vaccination and attend hospital approximately 11 times during this period. Standard safety assessments will be performed throughout the trial and at each clinic visit patients will be asked to provide research blood samples. These samples will be used to monitor the effects of the vaccine on the patient's immune system.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed NPC in which the presence of EBV has been confirmed in the tumour by immunohistochemistry for viral antigens or EBV early RNA (EBER) fluorescent in situ hybridisation (FISH).
  2. Patients in remission or with current disease for whom no standard therapy is currently appropriate or required.
  3. Patients who have received primary treatment for their malignancy (radiotherapy ± chemotherapy) and up to one additional second-line course of therapy.
  4. Life expectancy of at least 6 months.
  5. World Health Organisation (WHO) performance status of 0 or 1 (Appendix 1).
  6. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day 1) before the patient receives their first vaccination with MVA-EBNA1/LMP2.

    Laboratory Test Value required Haemoglobin (Hb) ≥10.0 g/dL, Lymphocyte count ≥0.5 x 10^9/L after ≥ 6 weeks have elapsed from completion of chemotherapy, Absolute neutrophil count (ANC) ≥1.0 x 10^9/L, Platelet count ≥ 75 x 10^9/L, Serum bilirubin ≤1.5 x upper limit of normal (ULN), Alkaline phosphatase (ALP) AND alanine aminotransferase (ALT) OR aspartate aminotransferase (AST) ≤ 2.5 x ULN, Calculated creatinine clearance ≥50 mL/min (uncorrected value)

  7. 18 years or over.
  8. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.

Exclusion criteria

  1. Radiotherapy, chemotherapy, endocrine therapy, immunotherapy or investigational medicinal products within 6 weeks prior to trial entry.
  2. Patients who, in the opinion of the investigator and multidisciplinary team managing the patient, may require another oncological treatment within 14 weeks of the first vaccination.
  3. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or Grade 1 toxicities, which in the opinion of the Investigator and the Sponsor should not exclude the patient.
  4. Current active auto-immune disease requiring therapy.
  5. Current active eczema requiring therapy.
  6. Allergy to eggs or egg products.
  7. History of anaphylaxis or severe allergy to previous vaccinations or medications. Patients with a documented history of allergy to gentamicin should be discussed with the Sponsor prior to trial entry.
  8. Previous splenectomy or splenic radiation, or with known splenic dysfunction.
  9. Receiving current immunosuppressive medication including systemic use of corticosteroids. Prophylactic use of inhaled steroids is permitted.
  10. Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) during the trial and for six months afterwards are considered eligible.
  11. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
  12. Major thoracic or abdominal surgery from which the patient has not yet recovered.
  13. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
  14. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
  15. Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), prior history of cardiac ischaemia or prior history of cardiac arrhythmia.
  16. Any other condition which in the Investigator‟s opinion would not make the patient a good candidate for the clinical trial.
  17. Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase Ib study of MVA-EBNA1/LMP2. Participation in an observational trial would be acceptable.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01800071

Locations
United Kingdom
University of Birmingham Recruiting
Edgbaston, Birmingham, United Kingdom, B15 2TT
Contact: Contact Person    0121 414 3791    n.m.steven@bham.ac.uk   
Principal Investigator: Neil Steven, Dr         
Royal Marsden Hospital Recruiting
Fulham Road, London, United Kingdom, SW3 6JJ
Contact: Contact Person       Kevin.Harrington@icr.ac.uk   
Principal Investigator: Kevin Harrington, Dr         
The Christie Hospital Recruiting
Manchester, United Kingdom, M20 4BX
Contact: Contact Person       lipwai.lee@christie.nhs.uk   
Principal Investigator: Lip Wai Lee, Dr         
Sponsors and Collaborators
Cancer Research UK
  More Information

No publications provided

Responsible Party: Cancer Research UK
ClinicalTrials.gov Identifier: NCT01800071     History of Changes
Other Study ID Numbers: CRUKD/13/001
Study First Received: February 25, 2013
Last Updated: October 7, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Cancer Research UK:
Nasopharyngeal cancer
Epstein Barr Virus Infections
Vaccination

Additional relevant MeSH terms:
Epstein-Barr Virus Infections
Carcinoma
Virus Diseases
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Herpesviridae Infections
DNA Virus Infections
Tumor Virus Infections
Neoplasms, Experimental
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on August 27, 2014