A Clinical Trial to Assess PVX7 Immunotherapy Regimens in Advanced Cervical Cancer Patients

A Randomized, Open-label Clinical Trial to Assess the Safety, Feasibility and Immunogenicity of Adjuvant PVX7 Immunotherapy Regimens in Advanced Cervical Cancer Patients

A Feasibility Trial of PVX7 vaccine in advanced cervical cancer patients who have completed primary definitive therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: PVX7

Detailed Description

A Feasibility Trial of PVX7 in advanced cervical cancer patients who have completed primary definitive therapy.

• Safety and immunogenicity study
• Patients are randomized in a 1:1 ratio to two cohorts, up to 16 patients in each of intramuscular or skin scarification vaccine injection, up to 32 patients total
• Human Immunodeficiency Virus (HIV)-negative patients only
• Treatment dose: Arm A: pBI-11 DNA (3 mg) twice via intramuscular (IM) injection, followed by one dose of TA-HPV (2.5x105 pfu) via skin scarification; Arm B: pBI-11 DNA (3 mg) twice, followed by one dose of TA-HPV (107 pfu) via IM injection
• Schedule for administration: PVX7 vaccination at weeks 1, 5, and 9
• Follow-up for 2 years per standard of care (SoC)

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Stephanie Gaillard, MD; Phone Number: 410-955-3774; Email: stephanie.gaillard@jhmi.edu
• Study Contact Backup: Name: Amy Deery, RN; Phone Number: (410) 502-0669; Email: ahorne1@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female subjects age 18 years or older with diagnosis of advanced cervical cancer and have completed primary treatment within the past 12 months.
• No history of or current evidence of residual disease or disease recurrence based on imaging and clinical assessments within 8 weeks of enrollment
• HIV uninfected
• Hepatitis B surface antigen negative
• Anti-hepatitis C (HCV) antibody negative or negative HCV polymerase chain reaction (PCR)
• Patients who are able and willing to comply with all study procedures and voluntarily sign an informed consent form
• Adequate organ function as defined by the following parameters:
• white blood cell count ≥ 3,000
• lymphocyte number ≥ 500
• absolute neutrophil count ≥ 1,000
• platelets ≥ 90,000
• hemoglobin ≥ 9
• total bilirubin <1.5 X upper limit of normal (ULN), <3 x ULN if Gilbert's disease
• Aspartate Transferase(AST)/Alanine Transaminase (ALT) <3 X ULN
• creatinine < 1.5 X ULN or estimated creatinine clearance ≥ 60 ml/min per Modified Cockcroft-Gault Formula
• Eastern Cooperative Oncology Group performance status of 0 or 1
• All clinically significant toxicities related to prior therapy should be less than or equal to Grade 1 at time of enrollment
• Ability and willingness for one month post vaccination to follow vaccine inoculation site care and avoid close social contact with children under 1 year old or close social or domestic contact with a pregnant woman or individuals at high risk of serious adverse effects of vaccinia virus, for instance, those with past or present eczema, or immunodeficiency states including HIV infection

Exclusion Criteria:

• Women of child-bearing potential (i.e., those who have had fertility-sparing procedures for the management of cervical cancer) will be excluded unless agreed to remain sexually abstinent or have a partner who is sterile (i.e. vasectomy), or use methods of contraception (e.g., oral contraception, barrier methods, spermicide, intrauterine device (IUD)), throughout the first 6 months of the study.
• Because there is a risk for adverse events in nursing infants, breastfeeding must be discontinued if the mother is treated on study.
• Diagnosed with a recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; patients diagnosed with acquired, hereditary, or congenital immunodeficiencies
• Diagnosis with a medical condition that requires systemic treatment with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), alkylating agents, antimetabolites, radiation, Tumor Necrosis Factor (TNF) inhibitors, or systemic corticosteroids, either chronically or within 30 days of first PVX7 vaccination.
• Administration of any blood product within 30 days of signing informed consent.
• Need for ongoing therapeutic anticoagulation during the study period due to concern for increased risk of bleeding.
• Previous severe allergic reaction or hypersensitivity to a vaccine or any of its components
• Participation in a study with an investigational compound or device within 30 days of signing informed consent
• History of seizures (unless seizure free for 5 years)
• Known active central nervous system disease
• Surgery within 30 days of first PVX7 vaccination, excluding minor procedures
• Diagnosis with an uncontrolled intercurrent illness including, but not limited to, ongoing, or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
• Diagnosis with an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis)
• History of myocarditis or pericarditis.
• Known underlying heart disease (e.g., cardiomyopathy, congestive heart failure, symptomatic arrhythmia not controlled by medication, unstable angina, history of acute myocardial infarction or cerebrovascular accident within the past 6 months).
• Patients and the patients close social, sexual, or domestic contacts may not have non-healed wounds or active exfoliative skin conditions such as: Eczema, Burns, Impetigo, Varicella-zoster virus infection, Herpes simplex virus infection, Severe acne, Severe diaper dermatitis with extensive areas of denuded skin, Psoriasis, Lichen planus, Darier disease (keratosis follicularis).
• History or presence of atopic dermatitis
• Inability or unwillingness to for one month post vaccination follow vaccine inoculation site care and avoid social contact with children under 1 year old or close social or domestic contact with a pregnant woman or individuals at high risk of serious adverse effects of vaccinia virus, for instance, those with past or present eczema, or immunodeficiency states including HIV infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pBI-11 DNA plus TA-HPV via Skin Scarification; Participants will receive pBI-11 DNA and TA-HPV via Skin Scarification	Drug: PVX7; PVX7 Immunotherapy; Other Names: pBI-11 DNA + TA-HPV
Experimental: pBI-11 DNA plus TA-HPV via IM Injection; Participants will receive pBI-11 DNA and TA-HPV via IM Injection	Drug: PVX7; PVX7 Immunotherapy; Other Names: pBI-11 DNA + TA-HPV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of PVX7 as assessed by adverse events	To assess the safety of PVX7 immunotherapy to patients with advanced cervical cancer who have completed primary therapy by evaluating Adverse Events (AEs).	12 months
Feasibility of PVX7	To assess the feasibility of PVX7 immunotherapy to patients with advanced cervical cancer who have completed primary therapy. Feasibility is measured by the ability of patients to receive all three doses of vaccine.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cellular Immune Response	To evaluate the systemic Human Papillomavirus (HPV)16/18 E6/E7-specific cellular immune responses to PVX7 immunotherapy by measuring the number of interferon gamma+ Cluster of Differentiation (CD)8 Tcells/mL with overlapping peptides covering HPV16/18 E6/E7 protein	12 months
Immune Response	To compare the route of administration associated with the greatest immune response in patients with advanced cervical cancer who have completed primary standard of care treatment	12 months
Presence of circulating HPV DNA	Measure presence of circulating HPV DNA load in blood pre- and post-PVX7 immunotherapy	12 months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Stephanie Gaillard, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: March 11, 2024
• First Submitted That Met QC Criteria: March 15, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms
• Other Study ID Numbers: J23105sIRB; IRB00388854 (Other Identifier: Johns Hopkins)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Participant data will be shared with NIH and other participating site.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No