HARE-40: HPV Anti-CD40 RNA Vaccine

Sponsor

University of Southampton (Other)

Overall Status

Recruiting

CT.gov ID

NCT03418480

Collaborator

BioNTech SE (Industry)

Enrollment

Location

Arms

89.7

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

HARE-40 is a phase I/II vaccine dose escalation study with two different arms: Arm 1A will perform intrapatient dose escalation in patients with previously treated HPV16+ Head & Neck Cancer using two dose cohorts to establish a safe, tolerable and recommended dose of HPV vaccine.

Arm 1B will perform intrapatient dose escalation in patients with advanced HPV16+ cancer (head and neck, anogenital, penile or cervical) using a single cohort to establish a safe, tolerable and recommended dose of HPV vaccine.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Squamous Cell Head and Neck Neoplasm Cervical Neoplasm Penile Neoplasms Malignant	Drug: BNT113	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

44 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Therapeutic HPV Vaccine Trial +/- Anti-CD40 in HPV-driven Squamous Cell Carcinoma

Actual Study Start Date :

Apr 11, 2017

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RNA Vaccine A Arm 1A: 15 (6+9) patients with previously treated HPV16+ head and neck squamous cell carcinoma receiving increasing doses of HPV vaccine.	Drug: BNT113 Intradermal vaccine
Experimental: RAN Vaccine B Arm 1B: 29 (15+14) patients with HPV16+ advanced disease receiving increasing doses of HPV vaccine.	Drug: BNT113 Intradermal vaccine

Arm

Intervention/Treatment

Experimental: RNA Vaccine A

Arm 1A: 15 (6+9) patients with previously treated HPV16+ head and neck squamous cell carcinoma receiving increasing doses of HPV vaccine.

Drug: BNT113

Intradermal vaccine

Experimental: RAN Vaccine B

Arm 1B: 29 (15+14) patients with HPV16+ advanced disease receiving increasing doses of HPV vaccine.

Drug: BNT113

Intradermal vaccine

Outcome Measures

Primary Outcome Measures

Dose Limiting Toxicity (DLT) according to CTCAE version 4.03 (Arm 1A) [3 months]
Safe and tolerable dose of clinically disease free patients (Arm 1A) - Determination of a suitable dose of HPV RNA

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Arm 1A:

Previous HPV16+ head and neck squamous cell carcinoma.
At least 12 months after completion of treatment.
Within 5 years of treatment completion.
Currently no clinical evidence of disease.
ECOG performance status 0 or 1.

Arm 1B:

HPV16+ head and neck, cervical, anogenital and penile carcinoma patients with recurrent disease.
Intention to treat is palliative.
Patient willing to have repeated tumour biopsies and re-biopsy deemed safe and feasible clinically.
Tissue samples available confirming HPV16+ disease to send to Central Laboratory.

Exclusion Criteria:

Patients unable to consent.
Any patient who has been previously vaccinated in any Arm of the trial.
<18 years
Systemic steroids (prednisolone >10 mg/day or equivalent) or other drugs with a likely effect on immune competence are forbidden during the trial. The predictable need of their use will preclude the patient from trial entry. Replacement steroids for adrenal insufficiency/failure are allowed.
Major surgery in the preceding three to four weeks, which the patient has not yet recovered from.
Patients who are of high medical risk because of non-malignant systemic disease, as well as those with active uncontrolled infection.
Patients with clinically relevant autoimmune disease will be excluded.
Patients who are known to be allergic to any of the excipients or constituents of the vaccine
Patients with any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial, such as concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/IV cardiac disease.
Current malignancies at other sites, with the exception of adequately treated basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years and are deemed at low risk for recurrence, are eligible for the study.
Patients who are serologically positive for or are known to suffer from Hepatitis B, C, Syphilis or HIV. Counselling will be offered to all patients prior to testing.
Patients who have a positive pregnancy test or who are breast feeding.
Fertile males or females who are unable or unwilling to use an effective method of birth control (eg. condom with spermicide, diaphragm with spermicide, birth control pills, injections, patches, intrauterine device, or intrauterine hormone-releasing system) during study treatment and until 28 days after patients finish the study treatment.
Elevated Liver Function Tests - ALT >3.0 x ULN, AST >3.0 x ULN, Bilirubin >3.0 x ULN.
Any other investigational drug within 28 days or 5 half-lives depending on what gives the longer range before the first treatment of this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univeristy Hospitals Southampton NHS Foundation Trust	Southampton	Hampshire	United Kingdom	SO16 6YD

Sponsors and Collaborators

University of Southampton
BioNTech SE

Investigators

Principal Investigator: Christian Ottensmeier, Prof, University of Liverpool
Principal Investigator: Ioannis Karydis, Dr, University Hospitals Southampton NHS Foundation Trust