A Vaccine (PDS0101) and Chemoradiation for the Treatment of Stage IB3-IVA Cervical Cancer, the IMMUNOCERV Trial

• Status: Recruiting
• Trial end date: 2024-03-08
• Target enrollment: 0
• Participant gender: Female

Summary

This phase IIA trial studies the effect of a vaccine (PDS0101) when given together with chemotherapy and radiation therapy (chemoradiation) in treating patients with stage IB3-IVA cervical cancer. Chemotherapy drugs, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. PDS0101 is a type of vaccine that is intended to help the immune system respond to human papillomavirus (HPV16)-infected cervical tumor cells. PDS0101 contains two active components: the first is called R-DOTAP (Versamune) and is included in the vaccine to boost the immune system's response against the HPV viral proteins and the second group of active components are selected small pieces of proteins (called peptides) taken from the HPV virus. Giving PDS0101 in combination with chemoradiation may work help to control cervical cancer.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Cisplatin; Vaccines

Criteria

Inclusion Criteria:

• Newly diagnosed locally advanced squamous cell carcinoma of cervix (Federation of Gynecology and Obstetrics [FIGO] 2018 stage IB3-IVA with primary tumor >= 5 cm and/or positive pelvic or periaortic nodal disease assessed by imaging)

• Histologic diagnosis of squamous cell carcinoma of the cervix

• Written informed consent before initiation of any study-related procedures

• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Alanine aminotransferase (ALT) =< 2-fold the upper limit of normal

• Aspartate aminotransferase (AST) =< 2-fold the upper limit of normal

• Alkaline phosphatase (alk phos) =< 2-fold the upper limit of normal

• Total bilirubin (total bili) =< 2-fold the upper limit of normal

• Creatinine =< 1.5

• Electrocardiogram (ECG) with no clinically significant findings (as assessed by the investigator) performed within 30 days of signing the informed consent form

• Absence of current malignancies at other sites, except for adequately treated basal or squamous cell carcinoma of the skin. Cancer survivors who have undergone potentially curative therapy for a prior malignancy who have no evidence of that disease for 5 years and who are deemed at low risk for recurrence are eligible for the study

Exclusion Criteria:

• Human immunodeficiency virus (HIV) infection, cellular immune deficiencies, hypogammaglobulinemia or dysgammaglobulinemia, or hereditary or congenital immunodeficiencies

• Prior diagnosis of hepatitis B or C (unless anti-hepatitis C therapy has produced a sustained virologic response)

• History of clinically significant autoimmune disease, Crohn's disease, or ulcerative colitis

• Serious concomitant disorder, including active systemic infection requiring treatment, as judged by the investigator

• Receipt of immunotherapy (e.g., interferons [IFNs], check-point inhibitors, tumor necrosis factor, interleukins, etc.) or biological response modifiers (granulocyte-macrophage colony-stimulating factor [GM-CSF], granulocyte colony-stimulating factor, macrophage colony-stimulating factor) within 4 weeks before the first study vaccination

• Receipt of chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug

• Current or recent use of physiologic doses of intra-articular, topical, or inhaled corticosteroids is acceptable

• History of previous therapeutic HPV vaccination (individuals who have been immunized with licensed prophylactic HPV vaccines [e.g., Silgard, Cervarix, Gardasil are not excluded)

• Known or suspected hypersensitivity to any component of the investigational product or contraindications to cisplatin (e.g., peripheral neuropathy grade =< 2 or ototoxicity =< grade 2 per Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0)

• Previous pelvic radiation therapy (RT)

• Previous chemotherapy for the cervix tumor

• Previous hysterectomy or will have a hysterectomy as part of their initial cervical cancer therapy

• Prior major surgery within 4 weeks of enrollment from which the patient has not recovered

• Other condition or prior therapy that, in the opinion of the Investigator, compromises the subject's welfare or may confound study results

• Concurrent participation in another therapeutic investigational study or use of another investigational drug within 6 months before the first study vaccination

• Previous enrollment in this study

• HPV genotyping is to be done from cervical swab samples. Enrollment will not require HPV testing

• Pregnancy: a female subject defined as a women of childbearing potential (WOCBP) who has a positive urine pregnancy test (e.g. within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required