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

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).

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.

Study Overview

• Status: Completed
• Conditions: Nasopharyngeal Cancer; Epstein Barr Virus Infections
• Intervention / Treatment: Drug: MVA-EBNA1/LMP2 vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre Cancer Centre
  • Glasgow, United Kingdom, G12 0YN
    • The Beatson West of Scotland Cancer
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
  • Birmingham
    • Edgbaston, Birmingham, United Kingdom, B15 2TT
      • University of Birmingham
  • London
    • Fulham Road, London, United Kingdom, SW3 6JJ
      • Royal Marsden Hospital

Participation Criteria

Eligibility Criteria

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

Description

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. History of Unstable Angina Pectoris or Myocardial Infarction up to 6 Months prior to trial entry.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response to three cycles of MVA-EBNA1/LMP2 vaccine	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.	pre-vaccination to 4 weeks post third vaccine
Occurrence of adverse events defined according to NCI CTCAE version 4.02		12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune memory and recall response to MVA-EBNA1/LMP2 vaccination	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	pre and post vaccines one and four.
Measurement of EBV genome levels in plasma before, during and after vaccination		pre- vaccination to 12 months post vaccination
Tumour response as determined by Immune-Related Response Criteria (irRC)		6 months

Collaborators and Investigators

• Sponsor: Cancer Research UK

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): March 10, 2017
• Study Completion (Actual): March 10, 2017

Study Registration Dates

• First Submitted: February 25, 2013
• First Submitted That Met QC Criteria: February 25, 2013
• First Posted (Estimate): February 27, 2013

Study Record Updates

• Last Update Posted (Actual): July 17, 2018
• Last Update Submitted That Met QC Criteria: July 16, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Nasopharyngeal cancer; Epstein Barr Virus Infections; Vaccination
• Additional Relevant MeSH Terms: Infections; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; DNA Virus Infections; Tumor Virus Infections; Herpesviridae Infections; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Virus Diseases; Epstein-Barr Virus Infections
• Other Study ID Numbers: CRUKD/13/001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No