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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2012 by University of Liverpool.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Aintree University Hospitals NHS Foundation Trust
Cancer Research UK
Advaxis, Inc.
Recipharm AB
Information provided by (Responsible Party):
Prof. Terry Jones, University of Liverpool
ClinicalTrials.gov Identifier:
NCT01598792
First received: May 11, 2012
Last updated: May 16, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
HPV-16 +ve Oropharyngeal Carcinoma
Biological: ADXS11-001
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by University of Liverpool:

Primary Outcome Measures:
  • Safety [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Translational [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 36
Study Start Date: February 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: ADXS11-001
    Escalating doses will be administered: 3.3 x 10e8,1 x 10e9 and 3.3 x 10e9 cfu to patient in 3 different groups. Dose-escalation will only occur if fewer than two patients in each group of six experience Dose Limiting Toxicity (DLT).
  Eligibility

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

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
  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: NCT01598792

Contacts
Contact: Gemma E Simpson, BSc +44 (0)151 794 8054 g.simpson@liv.ac.uk

Locations
United Kingdom
Velindre NHS Trust Not yet recruiting
Cardiff, United Kingdom, CF14 2TL
Contact: Mererid Evans         
Principal Investigator: Mererid Evans         
Aintree University NHS Foundation Trust Recruiting
Liverpool, United Kingdom, L9 7AL
Contact: Terence Jones         
Principal Investigator: Terence Jones         
The Royal Liverpool and Broadgreen University Hospitals NHS Foundation Trust Not yet recruiting
Liverpool, United Kingdom, L7 8XP
Contact: Terence Jones         
Principal Investigator: Terence Jones         
The Royal Marsden NHS Foundation Trust Not yet recruiting
London, United Kingdom, SW3 6JJ
Contact: Kevin Harrington         
Principal Investigator: Kevin Harrington         
Sponsors and Collaborators
University of Liverpool
Aintree University Hospitals NHS Foundation Trust
Cancer Research UK
Advaxis, Inc.
Recipharm AB
Investigators
Principal Investigator: Terence Jones, BSc,FRCS,MD University of Liverpool
  More Information

Additional Information:
No publications provided

Responsible Party: Prof. Terry Jones, Professor of Head and Neck Surgery, University of Liverpool
ClinicalTrials.gov Identifier: NCT01598792     History of Changes
Other Study ID Numbers: ISRCTN47069182, 2010-019916-20
Study First Received: May 11, 2012
Last Updated: May 16, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Carcinoma
Oropharyngeal Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Pharyngeal Neoplasms
Stomatognathic Diseases

ClinicalTrials.gov processed this record on October 20, 2014