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Trial registered on ANZCTR


Registration number
ACTRN12620000406909
Ethics application status
Approved
Date submitted
10/03/2020
Date registered
25/03/2020
Date last updated
9/05/2022
Date data sharing statement initially provided
25/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase Ib, single centre, open label study of a therapeutic Human Papillomavirus (HPV) DNA vaccine co-administered with an anti-PD-L1 immunotherapy, Durvalumab (MEDI4376), for recurrent and/or metastatic HPV-related Head and Neck Cancer
Scientific title
Open label, single arm, single centre study to evaluate the safety/tolerability, immunogenicity and preliminary efficacy of AMV002 when co-administered with anti-PD-L1 immunotherapy, Durvalumab (MEDI4736), in patients with recurrent and/or metastatic HPV-related, p16 positive oropharyngeal squamous cell carcinoma (OPSCC).
Secondary ID [1] 300755 0
Nil known
Universal Trial Number (UTN)
U1111-1249-4851
Trial acronym
DURVAX
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Head and Neck Cancer 316604 0
HPV 316605 0
Condition category
Condition code
Cancer 314835 314835 0 0
Head and neck
Infection 314947 314947 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Active treatment:
HPV DNA Vaccine (AMV002) - 1 mg/patient Intradermal Injection (ID) on Days 0, 28,56
Durvalumab (MEDI4736) - 10mg/kg Intravenous Infusion (IV) Days 7 and 28
Durvalumab (MEDI4736) - 1500mg IV Day 56
All interventions will administered at the oncology day-care by experienced oncology nurses

Maintanence
Durvalumab (MEDI4736) - 1500mg IV from day 84, every four weeks for 12 months
Treatment will be administered at the Oncology Day care by experienced oncology nurses
Intervention code [1] 317087 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323186 0
Explore the possibility of any indications of a response signal, therefore the statistical analysis will be descriptive:
Adverse Events: Incidence and Severity both Local and systemic.
Known local reactions at site of vaccination include: pain, tenderness, erythema, swelling, ulceration, scabs, redness, induration, ecchymosis, oedema, itching and paraesthesia).
Known Systemic reactions include fatigue myalgia, malaise, fever, rigors, arthralgia, nausea, diarrhoea, light headedness, dizziness, hypersensitivity, and headache).
Treatment emergent changes (Vital signs, clinical lab tests and clinical physical exams)
Serious Adverse Events: Incidence

All AEs and SAEs will be assessed by vital signs, clinical lab tests, clinical physical exams, photographic records (photos will be taken of site of injection), and patient self reported AEs and SAEs
Timepoint [1] 323186 0
Every available time point and as a change from baseline.
Time points:
Baseline
Active treatment: Day 0, 7, 28,35, 56, 63
Maintenance: Day 84, 112, 140, 168, 196, 224, 252, 280, 308, 336, 364, 392, End of study
Primary outcome [2] 323187 0
Changes in Immunogenicity:
Changes in T-Cell and/or antibody responses to HPV-16 as measured by ELISA and ELISPOT assay
Timepoint [2] 323187 0
Baseline, Day 84
Secondary outcome [1] 381111 0
Changes in development of anti-drug antibodies to durvalumab (MEDI4736) as measured by ADA serum assays
Timepoint [1] 381111 0
Baseline to Day 168

Eligibility
Key inclusion criteria
Histologically or cytologically-confirmed recurrent or metastatic or unknown primary of presumed, oropharyngeal squamous cell carcinoma (OPSCC).

Previously received curative or palliative treatment which may include any of the following: surgery, chemotherapy and/or radiotherapy (RT) or presenting with known metastatic disease.

Have results from local testing of HPV positivity for oropharyngeal cancer defined as a positive test for HPV16 DNA or HPV16 mRNA or p16 immunohistochemistry (IHC) testing using CINtec® p16 Histology assay and a 70% cut-off point. If HPV status has previously been tested using one or more of these procedures, no retesting is required, however HPV16 DNA or HPV16 mRNA testing may be performed on archived paraffin-embedded tumour tissue if not previously done.

Confirmation of PD-L1 Status. (Patients with equal to or greater than 25% of tumour cells with membrane staining of any intensity will be considered PD-L1 positive while those with 0% to 24% of tumour cells with membrane staining will be considered PD-L1 negative).

World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 at enrollment.

Able to communicate effectively with study personnel and is considered reliable, willing, and cooperative in terms of compliance with the protocol requirements.

Written informed consent and any locally-required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.

Aged 18 years or older at the time of informed consent.

Males who are not surgically sterile must use a condom from screening through to 90 days after the last dose of Durvalumab, unless they have a female partner who is surgically sterile or post-menopausal. They must refrain from fathering a child during this time.

Women of child-bearing potential (WOCBP) must use highly effective contraceptive measures (failure rate of < 1% per year when used consistently and correctly) and intend to continue use contraception for at least 90 days following completion of treatment. Highly effective contraceptive measures could include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone releasing system, bilateral tubal occlusion, vasectomized partner, and sexual abstinence.

Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.

Participant in otherwise general good health based on medical history and physical examination.

Body weight > 30kg.

Adequate normal organ and marrow function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck, including patients with Head and Neck Squamous Cell Carcinoma (HNSCC) of unknown primary or non-squamous histologies (e.g., nasopharynx or salivary gland), not specified in the inclusion criteria.

Received any prophylactic or therapeutic vaccine within 28 days, or investigational drug within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment.

Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study.

Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies, other investigational agent) 21 days prior to the first dose of study drug or 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug for patients who have received prior TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C). If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca/MedImmune and the Investigator.

Any previous treatment with a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD1) or programmed death ligand 1 (PD-L1) inhibitor, including Durvalumab.

Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) equal to or greater than 470 ms calculated from 3 electrocardiograms (ECGs) (within 15 minutes at 2-5 minutes apart).

Current or prior use of immunosuppressive medication within 28 days before the first dose of study treatment, with the exceptions of intranasal, inhaled, injected or topical corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are also an exception to this criterion.

Any unresolved toxicity equal to or great than NCI CTCAE Grade 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria

Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.

Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.

Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.

History of allogenic organ transplantation.

Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]).

Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent

History of another primary malignancy except for
- Malignancy treated with curative intent and with no known active disease for at least 5 years before the first dose of IP and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease

History of leptomeningeal carcinomatosis

Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry

History of autoimmunity or active primary immunodeficiency

Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.

Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of Durvalumab.

Pregnant as confirmed by a positive serum beta human chorionic gonadotropin (ß-HCG) pregnancy test at Screening or subsequent clinic visit.

Inadequate venous access to allow collection of blood samples.

Birthmarks, tattoos, wound or other skin conditions on the forearms that could reasonably obscure injection site reactions.

Received medication known to have anti-HPV activity within 28-days of screening (prior vaccination with HPV prophylactic vaccines is not an exclusion criterion for this study).

Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), known positive Hepatitis B virus surface antigen (HBsAg), Hepatitis C virus (HCV), or Human Immunodeficiency virus (HIV) positive for HIV 1/2 antibodies.

Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

Prior randomisation or treatment in a previous Durvalumab clinical study regardless of treatment arm assignment.

Unwilling to abstain from blood donation during the course of the study, and/or has donated blood or plasma within 60 days prior to the Screening visit.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive summary of safety, tolerability, immunogenicity and exploratory efficacy endpoints

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/04/2020
Actual
4/08/2020
Date of last participant enrolment
Anticipated
25/06/2021
Actual
13/07/2021
Date of last data collection
Anticipated
15/08/2022
Actual
31/01/2022
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 16104 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 29619 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 305215 0
Charities/Societies/Foundations
Name [1] 305215 0
Princess Alexandra Hospital Research Foundation
Country [1] 305215 0
Australia
Funding source category [2] 305216 0
Commercial sector/Industry
Name [2] 305216 0
AstraZenica Pty Ltd
Country [2] 305216 0
Australia
Funding source category [3] 305217 0
Commercial sector/Industry
Name [3] 305217 0
Jingang Medicine (Australia)
Country [3] 305217 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
University of Queensland QLD 4072
Country
Australia
Secondary sponsor category [1] 305574 0
None
Name [1] 305574 0
Address [1] 305574 0
Country [1] 305574 0
Other collaborator category [1] 281234 0
Hospital
Name [1] 281234 0
Princess Alexandra Hospital
Address [1] 281234 0
199 Ipswich Road
Woolloongabba 4103
Queensland
Country [1] 281234 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305565 0
Metro South Hospital and Health Services HREC
Ethics committee address [1] 305565 0
Ethics committee country [1] 305565 0
Australia
Date submitted for ethics approval [1] 305565 0
Approval date [1] 305565 0
06/12/2018
Ethics approval number [1] 305565 0
AM/2019/qMS/47239

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100790 0
Prof Sandro Porceddu
Address 100790 0
Director Radiation Oncology Research | Cancer Services
Princess Alexandra Hospital | Metro South Health
199 Ipswich Road
Woolloongabba
QLD 4102
Country 100790 0
Australia
Phone 100790 0
+61 07 3176 7853
Fax 100790 0
+61 07 3176 1983
Email 100790 0
sandro.porceddu@health.qld.gov.au
Contact person for public queries
Name 100791 0
Sandro Porceddu
Address 100791 0
Director Radiation Oncology Research | Cancer Services
Princess Alexandra Hospital | Metro South Health
199 Ipswich Road
Woolloongabba
QLD 4102
Country 100791 0
Australia
Phone 100791 0
+61 07 3176 7853
Fax 100791 0
+61 07 3176 1983
Email 100791 0
sandro.porceddu@health.qld.gov.au
Contact person for scientific queries
Name 100792 0
Sandro Porceddu
Address 100792 0
Director Radiation Oncology Research | Cancer Services
Princess Alexandra Hospital | Metro South Health
199 Ipswich Road
Woolloongabba
QLD 4102
Country 100792 0
Australia
Phone 100792 0
+61 07 3176 7853
Fax 100792 0
+61 07 3176 1983
Email 100792 0
sandro.porceddu@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All individual patient data collected during trial in summary
When will data be available (start and end dates)?
immediately following publication, no end date
Available to whom?
researchers who provide a methodogically sound proposal
Case by case basis
Available for what types of analyses?
Sub study
meta analysis
How or where can data be obtained?
subject to approval by PI - email PI: Sandro.Porceddu@health.qld.gov.au


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.