Safety Study of Recombinant Listeria Monocytogenes(Lm)Based Vaccine Virus Vaccine to Treat Oropharyngeal Cancer (REALISTIC:)

May 17, 2016 updated by: Prof. Terry Jones, University of Liverpool

REALISTIC: A Phase I, Dose Escalation Trial Of Recombinant Listeria Monocytogenes (Lm)-Based Vaccine Encoding Human Papilloma Virus Genotype 16 Target Antigens (ADXS11-001) In Patients With HPV-16 +ve Oropharyngeal Carcinoma

It is the investigators intention to investigate whether a specially designed vaccine, based on a genetically modified strain of the bacterium Listeria monocytogenes and called ADXS11-001 is safe to use and is able to boost the immune system of patients presenting with Human Papilloma Virus (HPV) associated oropharyngeal cancer (OPSCC). It is hoped that the vaccine will boost the immune system so that immune cells with cell killing properties are able to attack any cancer cells remaining after the patients have been treated. However, the vaccine is so novel the investigators are not sure whether it is able to do this and before they can answer that question in a larger group of patients they need to make sure that the vaccine is safe to use and has some effect on the immune system in the patients for whom they intend its ultimate use. In a previous study, patients with incurable cervix cancer which is caused by the same virus, were vaccinated with ADXS11-001. Although all patients vaccinated experienced flu-like symptoms, patients tolerated the vaccine well with no patient suffering long term adverse effects of vaccination. However, because the patients and cancer type was so different in this earlier study, the investigators need to test whether ADXS11-001 is also safe in patients with HPV associated OPSCC. That said, the earlier study guided the dosing schedule for the current study and patients entering the REALISTIC trial will receive lower doses than those administered to patients in the earlier cervix cancer study. It is hoped that by doing this, patients will experience fewer side effects of vaccination without reducing the chances of stimulating the immune system.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Cardiff, United Kingdom, CF14 2TL
        • Velindre NHS Trust
      • Liverpool, United Kingdom, L7 8XP
        • The Royal Liverpool and Broadgreen University Hospitals NHS Foundation Trust
      • Liverpool, United Kingdom, L9 7AL
        • Aintree University NHS Foundation Trust
      • London, United Kingdom, SW3 6JJ
        • The Royal Marsden NHS Foundation Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Histologically confirmed HPV-16 +ve, p16 +ve OPSCC.
  • Patients in remission from disease, i.e. complete response (CR) or unconfirmed complete response (CRu) in the case of non-surgical treatment or complete macroscopic resection of tumour and associated cervical lymph nodes in patients undergoing surgery.
  • Completion of standard therapy for malignancy at least 6 weeks before trial entry.
  • A positive result following anergy testing.
  • Written informed consent and the ability of the patient to co-operate with treatment and follow up must be ensured and documented.
  • Age greater than 18 years.
  • World Health Organisation (WHO) performance status of 0 or 1.
  • Life expectancy of at least 12 months.
  • Haematological and biochemical indices (these measurements must be performed within 8 days prior to the patient going on study):
  • Haematological:

Haemoglobin (Hb) > 10.0 g/dl Neutrophils ≥ 1.5 x 10e9/L Platelets (Plts) ≥ 100 x 10e9/L

  • Baseline liver function tests:

Serum bilirubin ≤ 1.5 x upper normal limit Serum alkaline phosphatase, alanine amino-transferase (ALT) and/or aspartate amino-transferase (AST) < 1.5 x ULN.

  • Baseline renal function test:

Calculated creatinine clearance > 50ml/min (uncorrected value) or isotope clearance measurement > 50ml/min.

  • Female patients of child-bearing potential are eligible, provided they have a negative serum pregnancy test prior to enrolment and agree to use appropriate medically approved contraception during the study up to six months after the last vaccination Male patients must agree to use appropriate medically approved contraception during the study up to six months after the last vaccination.

Exclusion Criteria:

  • Receiving, or having received, chemotherapy or radiotherapy within 6 weeks of trial entry.
  • Having undergone surgery +/- PORT within 6 weeks of trial therapy
  • A negative result following anergy testing.
  • Known chronic active infection with Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
  • Current active autoimmune disease.
  • Current active skin diseases requiring therapy (psoriasis, eczema etc).
  • Ongoing active infection.
  • History of anaphylaxis or severe allergy to vaccination.
  • Previous myeloablative therapy followed by an autologous or allogeneic haematopoietic stem cell transplant.
  • Patients who have had a splenectomy or splenic irradiation, or with known splenic dysfunction.
  • Receiving current immunosuppressive medication, including corticosteroids within 4 weeks of the first dose.
  • Pregnant and lactating women.
  • Ongoing toxic manifestations of previous treatment.
  • Major thoracic and/or abdominal surgery in the preceding four weeks from which the patient has not yet recovered.
  • Patients with any other condition which in the Investigator"s opinion would not make the patient a good candidate for the clinical trial.
  • Concurrent congestive heart failure or prior history of class III/ IV cardiac disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety
Time Frame: 12 months
Occurrence of drug-related grade 3 or 4 systemic or local adverse events (defined using the NCI Common Criteria Adverse Events (CTCAE) Version 4.03
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Translational
Time Frame: 24 Months
Demonstration by ELISPOT assay of the frequency of IFN-γ secreting lymphocytes recognising MHC class I and II-restricted epitopes within HPV-16 E& protein in peripheral blood at sequential time-points before, during and up to ten months after vaccination course. This protocol has been used by our group to demonstrate vaccine induced T cell responses in a previous HPV vaccine trial.
24 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Liverpool

Collaborators

Cancer Research UK
Liverpool University Hospitals NHS Foundation Trust
Advaxis, Inc.
Recipharm AB

Investigators

  • Principal Investigator: Terence Jones, BSc,FRCS,MD, University of Liverpool

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2012

Primary Completion (Actual)

November 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

May 11, 2012

First Submitted That Met QC Criteria

May 11, 2012

First Posted (Estimate)

May 15, 2012

Study Record Updates

Last Update Posted (Estimate)

May 18, 2016

Last Update Submitted That Met QC Criteria

May 17, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISRCTN47069182
  • 2010-019916-20 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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