Clinical Trials /

HPV Anti-CD40 RNA Vaccine

NCT03418480

Description:

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.

Related Conditions:
  • Anal Carcinoma
  • Cervical Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Penile Carcinoma
  • Vaginal Carcinoma
  • Vulvar Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: HPV Anti-CD40 RNA Vaccine
  • Official Title: Therapeutic HPV Vaccine Trial +/- Anti-CD40 in HPV-driven Squamous Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: RHMCAN0983
  • SECONDARY ID: 2014-002061-30
  • SECONDARY ID: ISRCTN51789191
  • NCT ID: NCT03418480

Conditions

  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasm
  • Cervical Neoplasm
  • Penile Neoplasms Malignant

Interventions

DrugSynonymsArms
HPV vaccineRNA Vaccine A

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
RNA Vaccine AExperimentalArm 1A: 15 (6+9) patients with previously treated HPV16+ head and neck squamous cell carcinoma receiving increasing doses of HPV vaccine.
  • HPV vaccine
RAN Vaccine BExperimentalArm 1B: 29 (15+14) patients with HPV16+ advanced disease receiving increasing doses of HPV vaccine.
  • HPV vaccine

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.

          -  Patient with a history of anaphylactic reactions or severe allergies are excluded.

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity (DLT) according to CTCAE version 4.03 (Arm 1A)
Time Frame:3 months
Safety Issue:
Description:Safe and tolerable dose of clinically disease free patients (Arm 1A) - Determination of a suitable dose of HPV RNA

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Southampton

Last Updated

January 31, 2018