HPV-16 +ve Oropharyngeal CarcinomaPhase 1REALISTIC:NCT01598792
Safety Study of Recombinant Listeria Monocytogenes(Lm)Based Vaccine Virus Vaccine to Treat Oropharyngeal Cancer
A Phase 1 study testing ADXS11-001 in people with HPV-16 +ve Oropharyngeal Carcinoma, run by University of Liverpool at 4 sites in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HPV-16 +ve Oropharyngeal Carcinoma
- What is being tested?
- ADXS11-001
- How many people
- 2 participants
- Where
- 4 sitesUnited Kingdom
- Study dates
- Feb 2012to Nov 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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
Trial locations and contacts
4 sites in 1 country.
United Kingdom4 sites
Velindre NHS Trust
Cardiff, CF14 2TL
The Royal Liverpool and Broadgreen University Hospitals NHS Foundation Trust
Liverpool, L7 8XP
Aintree University NHS Foundation Trust
Liverpool, L9 7AL
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
About this study
Official title: REALISTIC: A Phase I, Dose Escalation Trial Of Recombinant Listeria Monocytogenes (Lm)-Based Vaccine Encoding Human Papilloma Virus Genotype 16 Target Antigens (ADXS11-001) In Patients With HPV-16 +ve Oropharyngeal Carcinoma
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
- Being tested
- ADXS11-001
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADXS11-001Biological
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).
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
Secondary outcomes (1)
Translational
Demonstration by ELISPOT assay of the frequency of IFN-γ secreting lymphocytes recognising MHC class I and II-restricted epitopes within HPV-16 E\& protein in peripheral blood at sequential time-points before, during and up to ten months after vaccination course. This protocol has been used by our group to demonstrate vaccine induced T cell responses in a previous HPV vaccine trial.
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2012 (estimated)
- Study startFeb 2012
- Primary completionNov 2014
- Study completionNov 2014
Why it stopped: Patient 2 suffered DLT post-vaccination. The vaccine manufacturers withdrew support for the study on commercial grounds.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HPV-16 +ve Oropharyngeal CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liverpool
- Sponsor type
- University, hospital or other
- Collaborators
- Liverpool University Hospitals NHS Foundation Trust, Cancer Research UK, Advaxis, Inc., Recipharm AB
- Responsible party
- Principal investigator, Prof. Terry Jones, University of Liverpool
- Investigators
- Terence Jones, BSc,FRCS,MD, Principal investigator, University of Liverpool
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01598792
- Sponsor's protocol ID
- ISRCTN47069182
- Other IDs
- 2010-019916-20
- Acronym
- REALISTIC:
- Status last verified
- May 2016
- First submitted
- 11 May 2012
- Last updated
- 18 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REALISTIC: A Phase I, Dose Escalation Trial Of Recombinant Listeria Monocytogenes (Lm)-Based Vaccine Encoding Human Papilloma Virus Genotype 16 Target Antigens (ADXS11-001) In Patients With HPV-16 +ve Oropharyngeal Carcinoma
- ClinicalTrials.gov ID
- NCT01598792
- Acronym / sponsor ID
- REALISTIC: / ISRCTN47069182
- Conditions
- HPV-16 +ve Oropharyngeal Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Patient 2 suffered DLT post-vaccination. The vaccine manufacturers withdrew support for the study on commercial grounds.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of LiverpoolUniversity, hospital or other
- Collaborators
- Liverpool University Hospitals NHS Foundation Trust, Cancer Research UK, Advaxis, Inc., Recipharm AB
- Study start
- Feb 2012
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 15 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADXS11-001Escalating 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). | Biological | – |
Primary outcome
Safety
Time frame: 12 months
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
1 secondary outcome
Translational
Time frame: 24 Months
Results and safety
The study was stopped early (reason given: Patient 2 suffered DLT post-vaccination. The vaccine manufacturers withdrew support for the study on commercial grounds.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2016.
- Cancer Research UKLink provided by the sponsor.
- Liverpool Cancer Trials UnitLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Terence Jones, BSc,FRCS,MD principal investigator
University of Liverpool
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ADXS11-001 in people with HPV-16 +ve Oropharyngeal Carcinoma, run by University of Liverpool at 4 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Patient 2 suffered DLT post-vaccination. The vaccine manufacturers withdrew support for the study on commercial grounds.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2016.