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REALISTIC   

Title

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


Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs
I Treatment Closed 18 or over Aintree NHS Trust / University of Liverpool Eudract No: 2010-019916-20
Isrctn No: 47069182

Purpose

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.

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.


Trial Lead Organisations

LCTU / CR-UK


Trial Start Date

22/02/2012


Trial Coordinator

Gemma Nanson


Trial Coordinator Email Address

g.simpson@liv.ac.uk


Trial Coordinator Contact No

0151 794 8974


Website Treatment  

Patient will be randomised into one of three cohorts. Cohort 1 will recieve chemoradiotherapy or surgery and chemoradiotherapy. Cohort 2 will recieve radiotherapy or surgery plus radiotherapy. Cohort 3 will recieve Induction chemotherapy plus radiotherapy.

All cohorts will recieve 3 ADXS11-001 vaccine at 4 weekly intervals.

Trial Endpoints  


Primary Outcome  

  • Occurrence of drug-related grade 3 or 4 systemic or local adverse events (defined using the NCI Common Toxicity Criteria Adverse Events (CTCAE) version 3.0).
  • Occurrence of drug-related systemic reactions (e.g. transient fever).


Secondary Outcomes  

Demonstration of vaccine induced T cell responses.

Eligibility  

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):
    • Haemoglobin (Hb) > 10.0 g/dl
    • Lymphocytes > 1.0 x 109/L
    • Neutrophils ≥ 1.5 x 109/L
    • Platelets (Plts) ≥ 100 x 109/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.

UK: ENGLAND

  • Liverpool, Royal Liverpool University Hospital (Terry Jones)
  • Liverpool, University Hospital Aintree (Richard Shaw)

UK: WALES

  • Cardiff, University Hospital of Wales (Mererid Evans)

UK: ENGLAND

  • London, Royal Marsden Hospital (London) (Kevin Harrington)