Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Miss Gemma Simpson
ORCID ID
Contact details
University of Liverpool
Cancer Research Centre
200 London Road
Liverpool
L3 9TA
United Kingdom
-
g.simpson@liv.ac.uk
Additional identifiers
EudraCT number
2010-019916-20
ClinicalTrials.gov number
NCT01598792
Protocol/serial number
11160
Study information
Scientific title
A phase I, dose escalation trial of recombinant Listeria monocytogenes (Lm) based vaccine encoding human papilloma virus (HPV) serotype 16 target antigens (ADXS11001) in patients with HPV16 positive oropharyngeal squamous cell carcinoma
Acronym
REALISTIC
Study hypothesis
Human Papilloma Viruses (HPVs) are obligate human pathogens, some have the propensity to promote malignant transformations of their host cells. An example of this is HPV-16 in the oropharyngeal squamous cell carcinoma, which is seen in about 50-70% of cases although there is geographical variation.
Oropharyngeal squamous cell carcinoma (OPSCC) is on the increase in Europe and the United Kingdom, Cancer Research (UK) reported 953 new cases in 2005. If we accept that approx. 40-50% of these new cases may be due to HPV-16 infection, the resultant disease burden is about 380-480 new cases per annum in the UK. In contrast to other head and neck cancers, HPV related OPSCC occurs in younger patients, who are non-smokers and non-heavy drinkers.
ADXS11-001 (formerly Lovaxin C) is a bioengineered strain of living Listeria monocytogenes that induces a strong therapeutic immune response using multiple mechanisms of action. This vaccine secretes the tumour antigen HPV-16 E7 fused to an attenuated Lm virulence factor, Listeriolysin O (LLO), which has strong adjuvant properties.
If proved safe, there is a role for ADXS11-001 as a post-treatment adjuvant as part of a treatment de-escalation strategy in an attempt to reduce the adverse effects of current treatment strategies without compromising survival.
The REALISTIC trials' objective is to determine safety and to characterise the toxicity profile of ADXS11-001.
Ethics approval
First MREC, 20/09/2011, ref: GTAC 176
Study design
Non-randomised interventional screening treatment
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Screening
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Head and neck cancer
Intervention
ADXS11-001 - the patient will recieve 3 vaccinations. The vaccine will be given on Day 1 of each cycle. An interval of at least 28 days should occur between any two vaccinations. To proceed to the next vaccination the previous vaccination(s) must have been well tolerated. At each recruiting centre, the infusion will take place in an area specifically designated for phase I clinical trial patients to receive their experimental treatments. Follow Up Length: 12 months
Intervention type
Drug
Phase
Phase I
Drug names
ADXS11-001
Primary outcome measure
1. Safety
2. Occurrence of drug-related grade 3 or 4 systemic or local adverse events
Secondary outcome measures
1. Immunity
2. Demonstration by ELISPOT assay of the frequency of IFN secreting lymphocytes recognising MHC class
Overall trial start date
01/01/2012
Overall trial end date
01/01/2012
Reason abandoned (if study stopped)
Objectives no longer viable
Eligibility
Participant inclusion criteria
1. Histologically confirmed HPV-16 +ve, p16 +ve OPSCC
2. 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
3. Completion of standard therapy for malignancy at least 6 weeks before trial entry
4. A positive result following anergy testing
5. Written informed consent and the ability of the patient to co-operate with treatment and follow up must be ensured and documented
6. Age greater than 18 years
7. World Health Organisation (WHO) performance status of 0 or 1
8. Life expectancy of at least 12 months
9. Haematological and biochemical indices (these measurements must be performed within 8 days prior to the patient going on study)
10. Haematological:
10.1. Haemoglobin (Hb) > 10.0 g/dl
10.2. Neutrophils = 1.5 x 109/L
10.3. Platelets (Plts) = 100 x 109/L
11. Baseline liver function tests:
11.1. Serum bilirubin = 1.5 x upper normal limit
11.2. Serum alkaline phosphatase, alanine amino-transferase (ALT) and/or aspartate amino-transferase (AST) < 1.5 x ULN
12. Baseline renal function test: calculated creatinine clearance > 50ml/min (uncorrected value) or isotope clearance measurement > 50ml/min
13. 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
14.. Male patients must agree to use appropriate medically approved contraception during the study up to six months after the last vaccination
15. Lower age limit 18
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 36; UK Sample Size: 36
Participant exclusion criteria
1. Receiving, or having received, chemotherapy or radiotherapy within 6 weeks of trial entry.
2. Having undergone surgery +/- PORT within 6 weeks of trial therapy
3. A negative result following anergy testing
4. Known chronic active infection with Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV)
5. Current active autoimmune disease
6. Current active skin diseases requiring therapy (psoriasis, eczema etc)
7. Ongoing active infection
8. History of anaphylaxis or severe allergy to vaccination
9. Previous myeloablative therapy followed by an autologous or allogeneic haematopoietic stem cell transplant
10. Patients who have had a splenectomy or splenic irradiation, or with known splenic dysfunction
11. Receiving current immunosuppressive medication, including corticosteroids within 4 weeks of the first dose
12. Pregnant and lactating women
13. Ongoing toxic manifestations of previous treatment
14. Major thoracic and/or abdominal surgery in the preceding four weeks from which the patient has not yet recovered
15. Patients with any other condition which in the investigator's opinion would not make the patient a good candidate for the clinical trial
16. Concurrent congestive heart failure or prior history of class III/ IV cardiac disease
Recruitment start date
01/01/2012
Recruitment end date
01/01/2012
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University of Liverpool
Liverpool
L3 9TA
United Kingdom
Sponsor information
Organisation
University Hospital Aintree (UK)
Sponsor details
Fazakerley Hospital Lower Lane
Liverpool
L9 7AL
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
Clinical Trials Awards and Advisory Committee (UK) ref: C26837/A11920
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list