A Phase I, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic Human Papilloma Virus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC) after curative treatment.

Phase 1

Completed

• Conditions: HPV associated oropharyngeal squamous cell carcinoma; Cancer - Head and neck

• Registration Number: ACTRN12618000140257
• Lead Sponsor: Admedus Vaccines Pty Ltd

Brief Summary

The results of this open label first-in-human study evaluating three escalating doses of HPV DNA vaccine (AMV002), each given three times by ID injection to the forearm, administered four weeks apart to HPV-associated oropharyngeal squamous cell carcinoma patients in remission following curative treatment showed there are no concerns of safety up to a maximum dose of 4mg. The data from this study will inform dosing regimens in future studies to investigate AMV002 in the treatment of HPV-associated oropharyngeal squamous cell carcinoma.

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-01-30
• Study Completion: 2019-07-11
• Last Update Posted: 10 February 2020

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Diagnosed with a loco-regional confined HPV-associated OPSCC
2. 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 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.
3. Received curative intent treatment which may include any of the following: surgery, chemotherapy and/or radiotherapy (RT).
4. Completed curative treatment at least 12 weeks prior and undergone re-staging scans confirming loco-regional complete response and no evidence of distant disease.
5. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrolment
6. Able to communicate effectively with study personnel and is considered reliable, willing, and cooperative in terms of compliance with the protocol requirements.
7. Written informed consent signed prior to entry into the study.
8. Aged greater than or equal to 18 years at the time of informed consent.
9. Males who are not surgically sterile must use a condom through to study completion and for 1 month after the last vaccination, unless they have a female partner who is surgically sterile or post-menopausal. They must refrain from fathering a child during this time.
10. 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 of contraception for at least 3 months following the last vaccination. Highly effective contraceptive measures could include: combined (oestrogen 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.
11. Participant in otherwise general good health based on medical history and physical examination.

Exclusion Criteria

1. Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck, including participants 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.
2. Birthmarks, tattoos, wound or other skin conditions on the forearms that could reasonably obscure injection site reactions.
3. Inadequate venous access to allow collection of blood samples.
4. Breastfeeding or pregnant as confirmed by a positive serum beta human chorionic gonadotropin (ß-HCG) pregnancy test at Screening or subsequent clinic visits.
5. Current acute or chronic disease, other than the study indication, that would increase the expected risk of exposure to the investigational product or would be expected to interfere with the planned evaluations, in the judgment of the Investigator.
6. Received medication known to have anti-HPV activity within 28-days of screening
(Note: prior vaccination with HPV prophylactic vaccines is not an exclusion criterion for this study).
7. Laboratory blood values:
a) Haemoglobin <10.0 grams/decilitre (g/dL)
b) Neutrophil count <1000/mm3
c) Platelet count <80000/mm3
d) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN)
e) Amylase >1.5 times ULN (unless serum lipase is less than or equal to 1.5 times ULN)
f) Subjects with an estimated creatinine clearance of <60 mL/minute (min)
g) International Normalised Ratio (INR) > ULN
h) Hepatitis B surface antigen (HBsAg), Hepatitis C Virus (HCV) antibody or Human Immunodeficiency Virus (HIV) antibody positive.
8. Received any prophylactic or therapeutic vaccine, or investigational drug, within 4 weeks of first vaccination.
9. History of severe allergy (requiring hospital care), severe reaction to any drug or prior vaccination, or any known or suspected allergies or sensitivities to the study drug or its constituents.
10. 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

• Study Type: Interventional
• Study Design: Not specified