Dose escalation trial of Listeria monocytogenes based vaccine in patients with oropharyngeal squamous cell carcinoma

ISRCTN	ISRCTN47069182
DOI	https://doi.org/10.1186/ISRCTN47069182
EudraCT/CTIS number	2010-019916-20
ClinicalTrials.gov number	NCT01598792
Secondary identifying numbers	11160

Submission date: 31/10/2011
Registration date: 31/10/2011
Last edited: 02/09/2022

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-new-vaccine-treat-cancer-throat-that-may-be-caused-by-virus-hpv-realistic

Contact information

Miss Gemma Simpson
Scientific

University of Liverpool
Cancer Research Centre
200 London Road
Liverpool
L3 9TA
United Kingdom

Email	g.simpson@liv.ac.uk

Study information

Study design	Non-randomised interventional screening treatment
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Screening
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
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
Study acronym	REALISTIC
Study objectives	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(s)	First MREC, 20/09/2011, ref: GTAC 176
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Phase I
Drug / device / biological / vaccine name(s)	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 study start date	01/01/2012
Completion date	01/01/2012
Reason abandoned (if study stopped)	Objectives no longer viable

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 36; UK Sample Size: 36
Key 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
Key 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
Date of first enrolment	01/01/2012
Date of final enrolment	01/01/2012

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

University of Liverpool

Liverpool
L3 9TA
United Kingdom

Sponsor information

University Hospital Aintree (UK)
Hospital/treatment centre

Fazakerley Hospital Lower Lane
Liverpool
L9 7AL
England
United Kingdom

Website	http://www.aintreehospitals.nhs.uk/
"ROR"	https://ror.org/008j59125

Funders

Funder type

Government

Clinical Trials Awards and Advisory Committee (UK) ref: C26837/A11920

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results			02/09/2022	No	Yes

Editorial Notes

02/09/2022: Cancer Research UK plain English results link added.
04/04/2016: This trial closed early after one person had developed a serious infection caused by the vaccine and the company that makes the vaccine decided not to continue supplying it for the study.