Clinical Trials /

A Phase I Study of WT1 or NY-ESO-1 Vaccine and Nivolumab For Recurrent Ovarian Cancer

NCT02737787

Description:

The purpose of this study is to test the safety of a combination of an investigational WT1 vaccine and another drug called nivolumab. This is the first time that the WT1 vaccine and nivolumab are being used in combination. Also, to test the safety of a combination of an investigational NY-ESO-1 vaccine and another drug called nivolumab.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase I Study of WT1 or NY-ESO-1 Vaccine and Nivolumab For Recurrent Ovarian Cancer
  • Official Title: A Phase I Study of Concomitant WT1 Analog Peptide Vaccine or NY-ESO-1 Overlapping Peptides Vaccine in Combination With Nivolumab in Patients With Recurrent Ovarian Cancer Who Are in Second or Greater Remission

Clinical Trial IDs

  • ORG STUDY ID: 15-247
  • NCT ID: NCT02737787

Conditions

  • Ovarian Cancer
  • Fallopian Tube
  • Primary Peritoneal Cancer
  • Recurrent Ovarian Cancer

Interventions

DrugSynonymsArms
WT1 VaccineWT1 Vaccine and Nivolumab
NivolumabESO-1 Vaccine and Nivolumab
NY-ESO-1 VaccineESO-1 Vaccine and Nivolumab

Purpose

The purpose of this study is to test the safety of a combination of an investigational WT1 vaccine and another drug called nivolumab. This is the first time that the WT1 vaccine and nivolumab are being used in combination. Also, to test the safety of a combination of an investigational NY-ESO-1 vaccine and another drug called nivolumab.

Trial Arms

NameTypeDescriptionInterventions
WT1 Vaccine and NivolumabExperimentalPatients will initially receive 6 vaccinations over 12 weeks and 7 infusions of nivolumab every two weeks over 14 weeks. Toxicity assessments will be performed with each dose of vaccine, and 3 weeks after the completion of therapy at week 15. Patients who do not have disease progression at the week 15 evaluation are permitted to receive 4 additional vaccines administered approximately every 8 weeks. This maintenance vaccine course would begin at week 19.This cohort has completed recruitment.
  • WT1 Vaccine
  • Nivolumab
ESO-1 Vaccine and NivolumabExperimentalPatients will be vaccinated with the NY-ESO-1 OLP4 vaccine. Patients will receive a 1.0 mL emulsion of NY-ESO-1 OLPs with Poly-ICLC and Montanide.Nivolumab will be administered intravenously as a 30-minute infusion per institutional guidelines on weeks 0, 2, 4, 6, 8, 10 and 12.
  • Nivolumab
  • NY-ESO-1 Vaccine

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologic diagnosis of ovarian, fallopian tube or primary peritoneal cancer confirmed
             by pathology review at MSK.

          -  Patients will have relapsed at least once and returned to complete clinical remission
             after additional chemotherapy. Interval surgery is permitted.

          -  Complete clinical remission is defined as CA-125 within normal limits, examination and
             CT or MRI without objective evidence of disease (non specific abnormalities are
             permitted on radiologic imaging).

          -  Patients may sign screening consent during recurrence or at time of remission if they
             can start vaccine therapy within 4 months of completing chemotherapy.

          -  Testing of patient's archived (paraffin embedded, unstained slides) or freshly
             biopsied tumor nodules must be positive for WT1 (Cohort 1) or NY-ESO-1 (Cohort 2)
             protein expression. WT1 expression: Immunohistochemical analysis will be performed
             using the technique described by Dupont et al [58]. WT1 expression will be graded
             according to an adaptation of the German Immunoreactive Score (IRS). Only tumors with
             moderate to strong IRS scores (4-12) will be considered WT1 positive.

          -  NY-ESO-1 expression: Tissue available from primary and/or recurrent disease will be
             evaluated for tumor expression of NY-ESO-1 by immunohistochemical (IHC) and/or RT-PCR
             analysis will be performed using the technique described by Jungbluth et al

          -  Age ≥ 18 years

          -  Karnofsky performance status ≥ 70%

          -  Hematologic parameters: Absolute neutrophil count ≥ 1000/mcL, Platelets > 50 K/mcL.

          -  Biochemical parameters: Total bilirubin ≤ 1.5 mg/dl, AST and ALT ≤ 2.5 x upper limits
             of normal, Creatinine ≤ 1.5 mg/dl.

          -  Patient of childbearing potential must have a negative serum pregnancy test prior to
             study entry and must be practicing and effective form of birth control

        Exclusion Criteria:

          -  Pregnant or lactating women

          -  Patients with active infection requiring systemic antibiotics, antiviral, or
             antifungal treatments

          -  Patients with a serious unstable medical illness or another active cancer.

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

          -  Patients with known history of testing positive for human immunodeficiency virus (HIV)
             or known acquired immunodeficiency syndrome (AIDS).

          -  Patients with known active hepatitis B virus or hepatitis C virus acute or chronic
             infection.

          -  Patients with active known or suspected autoimmune disease (treated hypothyroidism is
             permitted to enroll)

          -  Patients with active interstitial pneumonitis.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose limiting toxicity (DLT)
Time Frame:30 days
Safety Issue:
Description:The first 3 patients will be observed for 30 days before enrolling the next 7 patients. Accrual will continue as patients become available after the first 3 patients are observed for 30 days. If >2/10 DLTs are observed then the study combination will not be considered safe.

Secondary Outcome Measures

Measure:immune response (cohort 2)
Time Frame:week 15
Safety Issue:
Description:Serologic IgM and IgG antibody responses will be measured by ELISA against each antigen
Measure:progression-free survival rate (cohort 2)
Time Frame:1 year
Safety Issue:
Description:Will evaluate PFS rate at 1-year using Kaplan Meier methodology

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Second or Greater Remission
  • WT1 Analog Peptide Vaccine
  • NY-ESO-1 Overlapping Peptides
  • GM-CSF
  • Nivolumab
  • 15-247

Last Updated

December 4, 2020