HARE-40: HPV Anti-CD40 RNA vaccinE (HARE-40)
Primary Purpose
Human Papilloma Virus Related Carcinoma, Head and Neck Neoplasm, Cervical Neoplasm
Status
Active
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
BNT113
Sponsored by
About this trial
This is an interventional treatment trial for Human Papilloma Virus Related Carcinoma
Eligibility Criteria
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
Sites / Locations
- Univeristy Hospitals Southampton NHS Foundation Trust
- The Christie NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
RNA Vaccine A
RAN Vaccine B
Arm Description
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
Arm 1B: 29 (15+14) patients with HPV16+ advanced disease receiving increasing doses of HPV vaccine. OPEN to recruitment
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Full Information
NCT ID
NCT03418480
First Posted
November 15, 2017
Last Updated
September 5, 2023
Sponsor
University of Southampton
Collaborators
BioNTech SE
1. Study Identification
Unique Protocol Identification Number
NCT03418480
Brief Title
HARE-40: HPV Anti-CD40 RNA vaccinE
Acronym
HARE-40
Official Title
Therapeutic HPV Vaccine (BNT113) Trial in HPV16 Driven Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 11, 2017 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southampton
Collaborators
BioNTech SE
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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, cervical and other) using a single cohort to establish a safe, tolerable and recommended dose of HPV vaccine.
Detailed Description
HARE-40 is a phase I/II vaccine dose escalation trial with two arms (Arm 1A and Arm 1B) in which we will test BNT113 as monotherapy. We will undertake a multi-centre phase I, open label trial in patients with previous HPV16+ HNSCC without current clinical evidence of disease (Arm 1A) and in patients with HPV16+ advanced disease (Arm 1B). The HPV16 antigen-specific immune response will be evaluated before and after treatment in circulating blood and, where samples have been collected, in tumour and skin biopsies.
Arms 1A and 1B will escalate BNT113 in each patient (intrapatient dose escalation) up to the specified target dose of the cohort to establish a safe, tolerable and recommended dose of BNT113 in patents who are disease free (Arm 1A) and those with advanced disease (Arm 1B).
Subset of patients in Arm 1B will also be assessed for response to the vaccine in terms of a significant increase of immune cells following BNT113 administration and according to irRECIST1.1 (all 29 patients including the expansion cohort) and other endpoints.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Papilloma Virus Related Carcinoma, Head and Neck Neoplasm, Cervical Neoplasm, Penile Neoplasms Malignant, Unknown Primary Tumors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RNA Vaccine A
Arm Type
Experimental
Arm Description
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
Arm Title
RAN Vaccine B
Arm Type
Experimental
Arm Description
Arm 1B: 29 (15+14) patients with HPV16+ advanced disease receiving increasing doses of HPV vaccine.
OPEN to recruitment
Intervention Type
Drug
Intervention Name(s)
BNT113
Intervention Description
Intradermal vaccine
Primary Outcome Measure Information:
Title
Dose Limiting Toxicity (DLT) according to CTCAE version 4.03 (Arm 1A)
Description
Safe and tolerable dose of clinically disease free patients (Arm 1A) - Determination of a suitable dose of HPV RNA
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian Ottensmeier, Prof
Organizational Affiliation
University of Liverpool
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Ioannis Karydis, Dr
Organizational Affiliation
University Hospitals Southampton NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Univeristy Hospitals Southampton NHS Foundation Trust
City
Southampton
State/Province
Hampshire
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
The Christie NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
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HARE-40: HPV Anti-CD40 RNA vaccinE
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