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

NCT ID: NCT01598792

Last Updated: 2016-05-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2014-11-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

ADXS11-001

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).

Intervention Type: BIOLOGICAL

Eligibility Criteria

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):
• 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.

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Liverpool University Hospitals NHS Foundation Trust

OTHER_GOV

Sponsor Role: collaborator

Cancer Research UK

OTHER

Sponsor Role: collaborator

Advaxis, Inc.

INDUSTRY

Sponsor Role: collaborator

Recipharm AB

UNKNOWN

Sponsor Role: collaborator

University of Liverpool

OTHER

Sponsor Role: lead

Responsible Party

Prof. Terry Jones

Professor of Head and Neck Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Terence Jones, BSc,FRCS,MD

Role: PRINCIPAL_INVESTIGATOR

University of Liverpool

Locations

Velindre NHS Trust

Cardiff, , United Kingdom

The Royal Liverpool and Broadgreen University Hospitals NHS Foundation Trust

Liverpool, , United Kingdom

Aintree University NHS Foundation Trust

Liverpool, , United Kingdom

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

Countries

United Kingdom

Related Links

http://www.cancerresearchuk.org/

Cancer Research UK

http://www.lctu.org.uk

Liverpool Cancer Trials Unit

Other Identifiers

2010-019916-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN47069182

Identifier Type: -

Identifier Source: org_study_id