Condition category
Cancer
Date applied
02/11/2016
Date assigned
15/12/2016
Last edited
11/08/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Miss Kerry-Ann Lee

ORCID ID

Contact details

Southampton Clinical Trials Unit
Southampton General Hospital
MP131
Tremona Road
Southampton
SO16 6YD
United Kingdom
+44 23 8120 3522
HARE-40@soton.ac.uk

Additional identifiers

EudraCT number

2014-002061-30

ClinicalTrials.gov number

Protocol/serial number

30900

Study information

Scientific title

Therapeutic HPV vaccine trial +/- anti-CD40 in HPV-driven squamous cell carcinoma

Acronym

HARE-40

Study hypothesis

The overall aim of this study is to establish a safe and tolerable dose of HPV mRNA vaccine and assess if there is evidence of clinical effect according to irRECIST 1.1.

Ethics approval

London - West London & GTAC Research Ethics Committee, 18/07/2016, ref: 16/LO/0567

Study design

Non-randomised; Interventional; Design type: Treatment, Prevention, Vaccine, Immunotherapy

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Cancer, Primary sub-specialty: Gynae; UKCRC code/ Disease: Cancer/ Malignant neoplasms of female genital organs, Cancer/ Malignant neoplasms of male genital organs, Cancer/ Malignant neoplasms of ill-defined, secondary and unspecified sites

Intervention

-

Intervention type

Drug

Phase

Phase I/II

Drug names

Primary outcome measures

Arm 1A:
The suitable dose of HPV mRNA vaccine is based on defined criteria for DLTs (dose limiting toxicities). This is measured by evaluation of DLTs until 28 days after last study treatment.

Arm 1B:
Disease control rate, defined as the rate of complete response, partial response or stable disease, is measured according to irRECIST 1.1 at the end of treatment CT scan at Day 85.

Secondary outcome measures

Arm 1A:
1. Adverse event rate is measured according to CTCAE v4.03 at the end of the trial until 28 days after last study treatment
2. Systemic levels of induced HPV-16 specific T-cell and B-cell immune responses are measured using specific biomarker tests at the end of study treatment
3. Duration of detectable vaccine-induced immune response is measured using specifically designed immune-assays at the end of study treatment
4. The clinical and immunological evaluation of DTH sites is assessed prior to vaccination and after the vaccination course, by clinical assessment and tissue biopsy, 48 hours post DTH injection

Arm 1B:
1. Adverse event rate is measured according to CTCAE v4.03 at the end of the trial until 28 days after last study treatment
2. Systemic levels of induced HPV-16 specific T-cell and B-cell immune responses are measured using specific biomarker tests during the course of trial at the end of study treatment
3. Duration of detectable vaccine-induced immune response is measured using specifically designed immune-assays, such as PBMCs during the course of the trial at the end of study treatment
4. The clinical and immunological evaluation of DTH sites is assessed prior to vaccination and after the vaccination course, by clinical assessment and tissue biopsy 48 hours post DTH injection
5. Percentage change in densities of immune cells in tumour tissue (where paired samples can be collected) is assessed using tumour tissue biopsies at baseline and follow-up (Day 85)
6. Numbers of immune cells is assessed by immunohistochemistry or flow cytometry at baseline and follow-up (Day 85)
7. Clinical response is measured according to irRECIST 1.1 at 85 days and 6 and 9 months
8. Disease control rate is measured according to irRECIST 1.1 at 6 and 9 months
9. Best overall response is measured according to irRECIST 1.1 at 9 months
10. Intra-tumoural levels of HPV16‐specific immune responses (where paired tumour samples can be collected) is measured using tumour tissue biopsies at baseline and follow-up (Day 85)
11. Safety/tolerability of HPV mRNA vaccine in terms of the adverse event rate is measured according to CTCAE v4.03 at 36 and 85 days
12. Grade 3 or above vaccine- or combination administration-related toxicity is measured within 90 days after the last administration of study drugs
13. Progression-Free Survival (PFS) is measured from baseline to date of disease progression or death, from any cause
14. Overall Survival (OS) is measured from baseline to date of disease progression or death, from any cause
15. Disease Specific Interval (DSI) is measured from baseline to date of disease progression or death, from any cause

Overall trial start date

01/03/2014

Overall trial end date

31/01/2021

Reason abandoned

Eligibility

Participant inclusion criteria

Inclusion Criteria Arm 1A:
1. Previous HPV16+ head and neck squamous cell carcinoma
2. At least 12 months after completion of treatment
3. Within 5 years of treatment completion
4. Currently no clinical evidence of disease
5. ECOG performance status 0 or 1
6. Able to provide written informed consent

Inclusion Criteria Arm 1B:
1. HPV16+ head and neck, cervical, anogenital and penile carcinoma patients with recurrent disease.
2. Intention to treat is palliative.
3. Patient willing to have repeated tumour biopsies and re-biopsy deemed safe and feasible clinically.
4. Tissue samples available confirming HPV16+ disease to send to Central Laboratory.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 153; UK Sample Size: 153

Participant exclusion criteria

1. Patients unable to consent
2. Under 18 years of age
3. Systemic steroids 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.
4. Major surgery in the preceding three to four weeks, which the patient has not yet recovered from
5. Patients who are of high medical risk because of non-malignant systemic disease, as well as those with active uncontrolled infection
6. 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
7. 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
8. 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
9. Patients who have a positive pregnancy test
10. Fertile males or females who are unable or unwilling to use a highly effective method of birth control (less than 1% per year, e.g. condom with spermicide, diaphragm with spermicide, birth control pills, injections, patches, intrauterine device, or intrauterine hormone-releasing system) during study treatment and until end of treatment +28 days (day 113)
11. Elevated Liver Function Tests – ALT, AST, Bilirubin
12. 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

Recruitment start date

01/01/2017

Recruitment end date

01/01/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Southampton Clinical Trials Unit
Southampton General Hospital Tremona Road
Southampton
SO16 6YD
United Kingdom

Sponsor information

Organisation

University Hospital Southampton NHS Foundation Trust

Sponsor details

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

European Commission

Alternative name(s)

EC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/01/2022

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

11/08/2017: Cancer Help UK lay summary link added. 06/06/2017: Internal review