Clinical Trials /

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

NCT04580771

Description:

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.

Related Conditions:
  • Cervical Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Vaccine (PDS0101) and Chemoradiation for the Treatment of Stage IB3-IVA Cervical Cancer, the IMMUNOCERV Trial
  • Official Title: IMMUNOCERV: Evaluating the Safety of Chemoradiation Combined With PDS0101 Immunotherapy in Treating Locally Advanced Cervical Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2019-1260
  • SECONDARY ID: NCI-2020-06810
  • SECONDARY ID: 2019-1260
  • NCT ID: NCT04580771

Conditions

  • Locally Advanced Cervical Squamous Cell Carcinoma, Not Otherwise Specified
  • Stage IB3 Cervical Cancer FIGO 2018
  • Stage II Cervical Cancer FIGO 2018
  • Stage IIA Cervical Cancer FIGO 2018
  • Stage IIA1 Cervical Cancer FIGO 2018
  • Stage IIA2 Cervical Cancer FIGO 2018
  • Stage IIB Cervical Cancer FIGO 2018
  • Stage III Cervical Cancer FIGO 2018
  • Stage IIIA Cervical Cancer FIGO 2018
  • Stage IIIB Cervical Cancer FIGO 2018
  • Stage IIIC Cervical Cancer FIGO 2018
  • Stage IIIC1 Cervical Cancer FIGO 2018
  • Stage IIIC2 Cervical Cancer FIGO 2018
  • Stage IVA Cervical Cancer FIGO 2018

Interventions

DrugSynonymsArms
CisplatinAbiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone''s Chloride, Peyrone''s Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, PlatosinTreatment (radiation therapy, cisplatin, PDS0101)
Liposomal HPV-16 E6/E7 Multipeptide Vaccine PDS0101mmunoMAPK-RDOTAP /HPV-16 E6/E7 Peptide Antigen Vaccine, PDS0101Treatment (radiation therapy, cisplatin, PDS0101)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVE:

      I. Evaluate the safety and toxicity profile of delivering the immune nanoparticle liposomal
      HPV-16 E6/E7 multipeptide vaccine PDS0101 (PDS0101) with standard-of-care chemoradiation
      (chemoRT) in patients with locally advanced cervical cancer.

      SECONDARY OBJECTIVES:

      I. Rate of complete metabolic response on day 170 (+/- 14 days) positron emission tomography
      computed tomography (PET CT).

      II. Rate of >= 90% gross tumor volume reduction day 35 magnetic resonance imaging (MRI) (+/-
      5 days).

      III. Report rates of local control (LC), progression-free survival (PFS), and overall
      survival (OS) at 12 and 18 months following chemoRT completion.

      IV. Long-term safety: rate of grade >= 3 chronic toxicity (from day 81 to completion of
      trial).

      EXPLORATORY HPV-SPECIFIC IMMUNE RESPONSE OBJECTIVES:

      I. Enzyme-linked immunosorbent spot (ELISpot) assays on interferon-gamma and granzyme B
      levels in E6/7-specific T cells isolated from peripheral blood mononuclear cells (PBMCs).

      II. Compare intratumoral T-cell receptor (TCR) clonality at baseline and end of treatment by
      TCR sequencing.

      III. Measure CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) from cervical brush samples
      by using markers of T-cell exhaustion (PD1, CTLA4) and T cell-activation (granzyme B, CD69+).

      IV. Assess the intestinal and cervical microbiome by analyzing rectal and cervical swab
      samples with 16s ribosomal ribonucleic acid (rRNA) sequencing.

      V. Additional assays such as circulating tumor cells, circulating cell-free tumor
      deoxyribonucleic acid (DNA) (ccfDNA), and other assays will be performed at the discretion of
      the principal investigator.

      OUTLINE:

      Patients undergo radiation therapy over 1 hour 5 days per week (Monday-Friday) for 5-7 weeks
      and receive cisplatin intravenously (IV) over 4 hours once per week (QW) during the 5 weeks
      of radiation therapy in the absence of disease progression and unacceptable toxicity.
      Patients also receive PDS0101 subcutaneously (SC) on days -10, 7, 28, 49, and 170 in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days, 1, 4, 6, 12, and 18
      weeks, and 18 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (radiation therapy, cisplatin, PDS0101)ExperimentalPatients undergo radiation therapy over 1 hour 5 days per week (Monday-Friday) for 5-7 weeks and receive cisplatin IV over 4 hours QW during the 5 weeks of radiation therapy in the absence of disease progression and unacceptable toxicity. Patients also receive PDS0101 SC on days -10, 7, 28, 49, and 170 in the absence of disease progression or unacceptable toxicity.
  • Cisplatin
  • Liposomal HPV-16 E6/E7 Multipeptide Vaccine PDS0101

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of grade >= 3 acute toxicity
Time Frame:Day -10 to day 80
Safety Issue:
Description:Measured from first vaccine injection up to 30 days following completion of chemoradiotherapy (chemoRT). Adverse events (AEs) will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Any AE that occurs between the first day of PDS0101 injection and up to 30 days following completion of chemoRT (~Day 80) will be considered as acute toxicity (AT).

Secondary Outcome Measures

Measure:Rate of complete metabolic response
Time Frame:Day 170
Safety Issue:
Description:Measured by positron emission tomography computed tomography (PET CT).
Measure:Rate of >= 90% gross tumor volume reduction
Time Frame:Day 35
Safety Issue:
Description:Measured by magnetic resonance imaging (MRI).
Measure:Rates of local control
Time Frame:At 12 and 18 months
Safety Issue:
Description:Will be represented by Kaplan-Meier curves.
Measure:Rates of progression-free survival
Time Frame:At 12 and 18 months
Safety Issue:
Description:Will be represented by Kaplan-Meier curves.
Measure:Rates of overall survival
Time Frame:At 12 and 18 months
Safety Issue:
Description:Will be represented by Kaplan-Meier curves.
Measure:Rate of grade >= 3 chronic toxicity
Time Frame:Day 81 to completion of trial
Safety Issue:
Description:AEs will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Chronic toxicity (CT) is any toxicity that occurs outside of the AT window (between Days 81 and study completion of the study).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

October 5, 2020