HPV induced cancers such as Head and Neck Squamous Cell Carcinoma (HNSCC), Anogenital Cancer, Cervical Cancer, Penile Cancer MedDRA version: 20.0 Level: PT Classification code 10067821 Term: Head and neck cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10008229 Term: Cervical cancer System Organ Class: 100000020977 MedDRA version: 20.0 Level: PT Classification code 10061424 Term: Ana
Conditions
Interventions
Product Name: RBLO15.1(LIP)/RBLO16.1(LIP)
Product Code: N/A
Pharmaceutical Form: Solution for injection
INN or Proposed INN: RBL015.1 (LIP)
CAS Number: N/A
Current Sponsor code: RBL015.1 (LIP)
Concent
Sponsors
University Hospital Southampton NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion 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. • Able to provide written informed consent. 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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 123 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: Arm 1A and 1B: • Patients unable to consent. • Any patient who has been previously vaccinated in any Arm of the trial. • 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 end of 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I objective: To establish a safe and tolerable dose of HPV mRNA vaccine (Arm 1A). Phase II objectives: • To assess if there is evidence of clinical effect (according to irRECIST 1.1 criteria) [Arm 1B]. • To assess if there is evidence of clinical effect in terms of a significant increase of immune cells following E6 and E7 HPV mRNA vaccine [Arm 1B]. ;Secondary Objective: • To establish the immunogenicity of the HPV mRNA vaccine and to characterise the immune responses (cellular and humoral) [Arms 1A and 1B]. • To evaluate and to characterise immune events in blood and tumour following administration of E6 and E7 HPV mRNA vaccine [Arm 1B] and to assess their linkage to immune events in the blood and tissue of the skin [Arm 1B ]. • To demonstrate that the tumour microenvironment can be manipulated by E6 and E7 HPV mRNA vaccine in advanced disease patients [Arms 1B]. This will be assessed by measuring immune cell numbers after intervention compared to baseline where two tissue samples can be collected. • To evaluate whether E6 and E7 HPV mRNA vaccine has detectable clinical effects in advanced HPV16-driven cancers and to assess if these clinical effects are linked with immune effects (blood; tissue where accessible) [Arm 1B]. ;Primary end point(s): Arm 1A: safety and Toxicity Arm 1B: Response according to irRECIST ;Timepoint(s) of evaluation of this end point: Arm 1A: Following cohort SRC meetings Arm 1B: End of Treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Arm 1A: • Adverse event rate according to CTCAE v4.03. • Systemic levels of induced HPV16-specific T-cell and B-cell immune responses. • Duration of detectable vaccine-induced immune responses (if appropriate). Arm 1B: • Adverse event rate according to CTCAE v4.03. • Systemic levels of induced HPV16-specific T-cell and B-cell immune responses. • Duration of detectable vaccine-induced immune responses (if appropriate). • Percentage change in densities of immune cells in tumour tissue (where paired samples can be collected). • Change in numbers of immune cells from screening to the end of treatment as assessed by immunohistochemistry or flow cytometry. • Clinical response according to irRECIST 1.1 at Day 85, and at months 6 and 9. • Disease control rate according to irRECIST 1.1 at months 6 and 9. • Best overall response (irRECIST 1.1). • Intra-tumoural levels of HPV16-specific immune responses (where paired tumour samples can be collected). • Safety/tolerability of HPV mRNA vaccine in terms of the adverse event rate according to CTCAE v4.03 at Day 85. • Grade 3 or above vaccine administration-related toxicity (within 90 days after the last administration of study drugs). • Progression-Free Survival (PFS). • Overall Survival (OS). • Disease Specific Interval (DSI). ;Timepoint(s) of evaluation of this end point: Arm 1A End of Treatment End of Treatment End of Treatment Arm 1B End of Treatment End of Treatment End of Treatment End of Treatment End of Treatment, 6 and 9 months Day 85,6&9 months 6&9 months Month 24 End of Treatment End of Treatment End of Treatment - within 90 days after the last administration of study drugs End of Treatment End of Treatment End of Treatment | — |
Countries
Spain, United Kingdom
Contacts
Public ContactKerry-Ann Lee
Southampton Clinical Trials Unit
Outcome results
None listed