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

NCT01598792 | Terminated Phase 1 DMC

• 2 other identifiers: ISRCTN470691822010-019916-20
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

HPV-16 +ve Oropharyngeal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety

  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

  12 months

Secondary Outcomes (1)

• Translational

  24 Months

Interventions

ADXS11-001 BIOLOGICAL

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 Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Liverpool: lead
• Liverpool University Hospitals NHS Foundation Trust: collaborator
• Cancer Research UK: collaborator
• Advaxis, Inc.: collaborator
• Recipharm AB: collaborator

Study Sites (4)

Velindre NHS Trust

Cardiff, CF14 2TL, United Kingdom

Location

The Royal Liverpool and Broadgreen University Hospitals NHS Foundation Trust

Liverpool, L7 8XP, United Kingdom

Location

Aintree University NHS Foundation Trust

Liverpool, L9 7AL, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

Related Links

• Cancer Research UK
• Liverpool Cancer Trials Unit

Study Officials

• Terence Jones, BSc,FRCS,MD

  University of Liverpool

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Head and Neck Surgery

Study Record Dates

• First Submitted: May 11, 2012
• First Posted: May 15, 2012
• Study Start: February 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: May 18, 2016

Record last verified: 2016-05

Locations

GB (4)