HARE-40: HPV Anti-CD40 RNA vaccinE

NCT03418480 | Completed Phase 1 DMC

• 3 other identifiers: RHMCAN09832014-002061-30ISRCTN51789191
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

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, cervical and other) using a single cohort to establish a safe, tolerable and recommended dose of HPV vaccine.

Conditions

Human Papilloma Virus Related Carcinoma; Head and Neck Neoplasm; Cervical Neoplasm; Penile Neoplasms Malignant; Unknown Primary Tumors

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT) according to CTCAE version 4.03 (Arm 1A)

  Safe and tolerable dose of clinically disease free patients (Arm 1A) - Determination of a suitable dose of HPV RNA

  3 months

Study Arms (2)

RNA Vaccine A

EXPERIMENTAL

Arm 1A: 15 (6+9) patients with previously treated HPV16+ head and neck squamous cell carcinoma receiving increasing doses of HPV vaccine. \- COMPLETE no longer recruiting

Drug: BNT113

RAN Vaccine B

EXPERIMENTAL

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

Drug: BNT113

Interventions

BNT113 DRUG

Intradermal vaccine

RAN Vaccine B; RNA Vaccine A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Southampton: lead
• BioNTech SE: collaborator

Study Sites (2)

Univeristy Hospitals Southampton NHS Foundation Trust

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Uterine Cervical Neoplasms; Penile Neoplasms; Neoplasms, Unknown Primary

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Penile Diseases; Male Urogenital Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Christian Ottensmeier, Prof

  University of Liverpool

  STUDY CHAIR

• Ioannis Karydis, Dr

  University Hospitals Southampton NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2017
• First Posted: February 1, 2018
• Study Start: April 11, 2017
• Primary Completion: November 1, 2023
• Study Completion: January 24, 2024
• Last Updated: February 7, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)