Condition category
Cancer
Date applied
31/10/2011
Date assigned
31/10/2011
Last edited
04/04/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

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 measures

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

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

http://www.aintreehospitals.nhs.uk/

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

Updated 04/04/2016: This trial closed early after one person had developed a serious infection caused by the vaccine and the company who makes the vaccine decided not to continue supplying it for the study.