Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 4 for:    PDS0101

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04580771
Recruitment Status : Not yet recruiting
First Posted : October 8, 2020
Last Update Posted : October 8, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
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 Drug: Cisplatin Biological: Liposomal HPV-16 E6/E7 Multipeptide Vaccine PDS0101 Radiation: Radiation Therapy Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: IMMUNOCERV: Evaluating the Safety of Chemoradiation Combined With PDS0101 Immunotherapy in Treating Locally Advanced Cervical Cancer
Estimated Study Start Date : October 30, 2020
Estimated Primary Completion Date : March 8, 2024
Estimated Study Completion Date : March 8, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cervical Cancer
Drug Information available for: Cisplatin

Arm Intervention/treatment
Experimental: Treatment (radiation therapy, cisplatin, PDS0101)
Patients 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.
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • 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
  • Platosin

Biological: Liposomal HPV-16 E6/E7 Multipeptide Vaccine PDS0101
Given SC
Other Names:
  • mmunoMAPK-RDOTAP /HPV-16 E6/E7 Peptide Antigen Vaccine
  • PDS0101

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation




Primary Outcome Measures :
  1. Rate of grade >= 3 acute toxicity [ Time Frame: Day -10 to day 80 ]
    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 :
  1. Rate of complete metabolic response [ Time Frame: Day 170 ]
    Measured by positron emission tomography computed tomography (PET CT).

  2. Rate of >= 90% gross tumor volume reduction [ Time Frame: Day 35 ]
    Measured by magnetic resonance imaging (MRI).

  3. Rates of local control [ Time Frame: At 12 and 18 months ]
    Will be represented by Kaplan-Meier curves.

  4. Rates of progression-free survival [ Time Frame: At 12 and 18 months ]
    Will be represented by Kaplan-Meier curves.

  5. Rates of overall survival [ Time Frame: At 12 and 18 months ]
    Will be represented by Kaplan-Meier curves.

  6. Rate of grade >= 3 chronic toxicity [ Time Frame: Day 81 to completion of trial ]
    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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04580771


Contacts
Layout table for location contacts
Contact: Ann H. Klopp 713-563-2444 aklopp@mdanderson.org

Locations
Layout table for location information
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Contact: Ann H. Klopp    713-563-2444      
Principal Investigator: Ann H. Klopp         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Ann H Klopp M.D. Anderson Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT04580771    
Other Study ID Numbers: 2019-1260
NCI-2020-06810 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2019-1260 ( Other Identifier: M D Anderson Cancer Center )
First Posted: October 8, 2020    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: October 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Squamous Cell
Uterine Cervical Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Cisplatin
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents