Clinical Trials /

NeoVax With Nivolumab in Patients With Ovarian Cancer

NCT04024878

Description:

This research study is evaluating a new type of vaccine called "Personalized NeoAntigen Cancer Vaccine" in combination with Nivolumab (Opdivo®) for ovarian cancer.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Fallopian Tube Carcinosarcoma
  • Ovarian Carcinoma
  • Ovarian Carcinosarcoma
  • Primary Peritoneal Carcinoma
  • Primary Peritoneal Carcinosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: NeoVax With Nivolumab in Patients With Ovarian Cancer
  • Official Title: NeoVax With Nivolumab in Patients With Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18-318
  • NCT ID: NCT04024878

Conditions

  • Ovarian Cancer

Interventions

DrugSynonymsArms
NivolumabOpdivoStanfard Platinum
NeoVaxStanfard Platinum

Purpose

This research study is evaluating a new type of vaccine called "Personalized NeoAntigen Cancer Vaccine" in combination with Nivolumab (Opdivo®) for ovarian cancer.

Detailed Description

      This research study is a Phase I clinical trial, which tests the safety of an investigational
      Personalized Cancer Vaccine in combination with Nivolumab (Opdivo®). "Investigational" means
      that the Personalized Cancer Vaccine is being studied. It also means that the U.S. Food and
      Drug Administration (FDA) has not approved the Personalized Cancer Vaccine as a treatment for
      any disease.

      The U.S. Food and Drug Administration (FDA) has not approved Nivolumab for this specific
      disease but it has been approved for other uses.

      The purpose of this study is to determine if it is possible to make and administer safely a
      vaccine against ovarian cancer by using information gained from specific characteristics of
      the participant's own ovarian cancer. It is known that ovarian cancers have mutations
      (changes in genetic material) that are specific to an individual patient and tumor. These
      mutations can cause the tumor cells to produce proteins that appear very different from the
      body's own cells. It is possible that these proteins used in a vaccine may induce strong
      immune responses, which may help the body fight tumor ovarian cancer cells. The study will
      examine the safety of the vaccine when given at several different time points and will
      examine the blood cells for signs that the vaccine induced an immune response.

      Ovarian cancer cells will be obtained from the tumor through a biopsy. The genetic material
      contained in the ovarian cancer cells will be examined for the presence of tumor-specific
      mutations. This information will be used to prepare small protein fragments, which are called
      "peptides". The vaccine will consist of up to 20 of these peptides as well as a drug that
      activates the immune system called Poly-ICLC.

      Poly-ICLC (also called Hiltonol) is an experimental "viral mimic" and an activator of
      immunity. Poly-ICLC binds proteins on the surface of certain immune cells to make it appear
      as if a virus is present. When the cells detect the vaccine, they think it is a virus and
      turn on the immune system. Poly-ICLC is a compound that has been used to help the body in its
      fight against cancer. Poly-ICLC will be mixed with NeoAntigen peptides and administered as an
      injection given underneath the skin. Poly-ICLC is an investigational drug, meaning the FDA
      has not approved it as a treatment for any disease.

      Nivolumab (Opdivo®) is an antibody that has been approved by the United States Food and Drug
      Administration (FDA) for the treatment of metastasic lung cancer, metastasic melanoma,
      advanced renal cell carcinoma, recurrent or metastasic carcinoma of the neck, hepatocellular
      carcinoma, advanced or metastasic urothelial carcinoma, metastasic colorectal cancer, and
      relapsed or progressed Hodgkin Lymphoma.

      An antibody is a common type of protein produced by your body that the immune system (a
      system that defends the body against potentially harmful particles) uses to find and destroy
      foreign molecules (particles not typically found in the body) such as bacteria and viruses.
      Antibodies can also be produced in the laboratory for use in treating patients. There are now
      several approved antibodies for the therapy of cancer and other diseases.

      Nivolumab is an antibody that acts against PD-1. PD-1 is a molecule that controls a part of
      the immune system by shutting it down. Researchers believe that one way cancers can escape
      the immune system could also be by blocking it out so. An antibody against PD-1 can stop PD-1
      from turning off the immune system, allowing the immune reaction to continue. The body's
      immune reaction may help the body to destroy cancer cells.
    

Trial Arms

NameTypeDescriptionInterventions
Stanfard PlatinumExperimentalA total of 5 NeoVax immunizations will be administered over a 3-week period Two booster vaccinations will be given at Week 12 Nivolumab administered by intravenous (IV) infusion over 30 minutes every 2 weeks.
  • Nivolumab
  • NeoVax
Stanfard Platinum with Surgical or Core Needle BiopsyExperimentalA total of 5 NeoVax immunizations will be administered over a 3-week period Two booster vaccinations will be given at Week 12 Nivolumab administered by intravenous (IV) infusion over 30 minutes every 2 weeks. Will undergo required surgical or core needle biopsy at first recurrence with progression free interval
  • Nivolumab
  • NeoVax

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of epithelial ovarian cancer, primary peritoneal or fallopian tube cancer.
             High grade serous, high grade endometrioid, clear cell and carcinosarcoma
             (carcinosarcomas only with high grade serous epithelial component) histologies are
             allowed. Low grade histologies and mucinous histology are not allowed.

          -  Participants must be classified into one of two cohorts:

          -  Cohort A: Patients with newly diagnosed stage IIIC or stage IV epithelial ovarian,
             fallopian tube, or primary peritoneal cancer who are planned to undergo neoadjuvant
             chemotherapy. Patients must be candidates for platinum-based chemotherapy and
             previously untreated. At the time of pre-screening consent, patients must have disease
             that is amenable to biopsy and are agreeable and can safely undergo biopsy.

          -  Cohort B: Patients with recurrent (first recurrence only) epithelial ovarian, primary
             peritoneal or fallopian tube cancer with platinum sensitive disease defined as disease
             progression greater or equal than 6 months but not more than 18 months after
             completion of their last dose of first line platinum chemotherapy. Prior hormonal
             therapy is allowed but no other therapy for recurrence is allowed, including no
             chemotherapy, no targeted therapy, and no antiangiogenic therapy. Maintenance therapy
             after first line chemotherapy is allowed. At the time of pre-screening consent,
             patients must have measurable disease by RECIST 1.1 and disease that is amenable to
             biopsy and are agreeable and can safely undergo biopsy.

          -  Eastern Cooperative Group (ECOG) performance status ≤2 (please see Appendix A)

          -  Age ≥18 years

          -  Patients must have adequate organ and bone marrow function:

               -  Haemoglobin ≥ 8.0 g/dL

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

               -  White blood cells (WBC) > 2x109/L

               -  Platelet count ≥ 100 x 109/L

               -  Total bilirubin ≤ 1.5 x institutional upper limit of normal

               -  AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver
                  metastases are present in which case it must be ≤ 5x ULN

               -  Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)

          -  Negative serum β-HCG or urine pregnancy test

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
             and other study procedures

          -  Women of childbearing potential (WOCBP) must agree to follow instructions for
             method(s) of contraception for the duration of study treatment with Nivolumab and 5
             months after the last dose of study treatment {i.e., 30 days (duration of ovulatory
             cycle) plus the time required for the investigational drug to undergo approximately
             five half-lives}.

        Patients of non-childbearing potential are defined as those fulfilling at least one of the
        following criteria:

          -  Have undergone a documented hysterectomy and/or bilateral oophorectomy;

          -  Have medically confirmed ovarian failure; or

          -  Achieved postmenopausal status, defined as follows: cessation of regular menses for at
             least 12 consecutive months with no alternative pathological or physiological cause;
             status may be confirmed by having a serum follicle-stimulating hormone (FSH) level
             confirming the post-menopausal state

        Exclusion Criteria:

          -  Non-epithelial tumors or ovarian tumors with low malignant potential (i.e. borderline
             tumors)

          -  Mucinous or low grade histologies (i.e. low grade serous or low grade endometrioid)

          -  Cohort A and B patients who have signed prescreening consent form and then, in the
             opinion of the investigator, have progressed after 3 or 4 cycles of platinum-based
             chemotherapy, are ineligible for the treatment part of the study and no vaccine will
             be manufactured

          -  Prior immunotherapy with IL-2, IFN-α, or anti-PD-1, anti-PD-L1, anti-PD-L2,
             anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (anti-CTLA-4) antibody
             (including Ipilimumab), or any other antibody or drug specifically targeting T cell
             co-stimulation or immune checkpoint pathways

          -  Major surgery (other than debulking surgery for ovarian, primary peritoneal or
             fallopian tube cancer) for any reason within 4 weeks prior to initiation of
             vaccination and/or incomplete recovery from surgery

          -  Known brain metastases or leptomeningeal metastases because of their poor prognosis
             and because patients often develop progressive neurologic dysfunction that would
             confound the evaluation of neurologic and other adverse events. A scan to confirm the
             absence of brain metastases is not required.

          -  Active or history of autoimmune disease (known or suspected). Exceptions are permitted
             for vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
             condition requiring only hormone replacement, psoriasis not requiring systemic
             treatment, or conditions not expected to recur in the absence of an external trigger.

          -  Have a condition requiring systemic treatment with either corticosteroids (> 10 mg
             daily prednisone equivalents) or other immunosuppressive medications within 14 days
             prior to the first dose of study drug (Nivolumab). Inhaled or topical steroids and
             adrenal replacement doses (≤ 10 mg daily prednisone equivalents) are permitted in the
             absence of active autoimmune disease.

          -  Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C,
             life-threatening illnesses unrelated to cancer, or any serious medical or psychiatric
             illness that could, in the investigator's opinion, interfere with participation in
             this study.

          -  Known allergy to tetanus toxoid

          -  Have an uncontrolled intercurrent illness including, but not limited to, ongoing or
             active infection requiring treatment, symptomatic congestive heart failure, unstable
             angina pectoris, cardiac arrhythmia.

          -  Have any underlying medical condition, psychiatric condition, or social situation
             that, in the opinion of the investigator, would compromise study administration as per
             protocol or compromise the assessment of AEs.

          -  Pregnant women are excluded from this study because Nivolumab, personalized neoantigen
             peptides, and Poly-ICLC are agents with unknown risks to the developing fetus.

          -  Nursing women are excluded from this study because there is an unknown but potential
             risk of adverse events in nursing infants secondary to treatment of the mother with
             Nivolumab, personalized neoantigen peptides, and Poly-ICLC.

          -  Have a history of an invasive malignancy, except for the following circumstance:
             individuals with a history of invasive malignancy are eligible if they have been
             disease-free for at least 2 years or are deemed by the investigator to be at low risk
             for recurrence of that malignancy; individuals with the following cancers are eligible
             if diagnosed and treated carcinoma in situ of the breast, oral cavity or cervix,
             localized prostate cancer, basal cell or squamous cell carcinoma of the skin.

          -  Participants who are receiving any other investigational agents
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of patients pre-srceened who have enough neoantigens for generation of the vaccine, are not platinum refractory, and who initiate vaccination
Time Frame:2 years
Safety Issue:
Description:To demonstrate that regimen of NeoVax with Nivolumab is feasible and safe for the treatment of patients with ovarian cancer.

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:2 years
Safety Issue:
Description:
Measure:Duration of Response
Time Frame:2 years
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:2 Years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Ovarian Cancer

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