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.
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
Drug | Synonyms | Arms |
---|
WT1 Vaccine | | WT1 Vaccine and Nivolumab |
Nivolumab | | ESO-1 Vaccine and Nivolumab |
NY-ESO-1 Vaccine | | ESO-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
Name | Type | Description | Interventions |
---|
WT1 Vaccine and Nivolumab | Experimental | Patients 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. | |
ESO-1 Vaccine and Nivolumab | Experimental | Patients 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: | Active, not 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
August 3, 2021