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

Ovarian Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02737787
• Other study ID #: 15-247
• Status: Completed
• Phase: Phase 1
• Start date: April 2016
• Est. completion date: April 6, 2023

Study information

• Verified date: April 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: April 6, 2023
• Est. primary completion date: April 6, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube
• Ovarian Cancer
• Ovarian Neoplasms
• Primary Peritoneal Cancer
• Recurrence
• Recurrent Ovarian Cancer

Intervention

Biological:
• WT1 Vaccine

Drug:
• Nivolumab
Nivolumab will be administered intravenously as a 30-minute infusion per institutional guidelines on weeks 0, 2, 4, 6, 8, 10 and 12.

Biological:
• NY-ESO-1 Vaccine
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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Commack (All Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (All Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (All Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (All Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York
United States	Memorial Sloan Kettering Nassau (All protocol activities)	Rockville Centre	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity (DLT)	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.	30 days
Secondary	immune response (cohort 2)	Serologic IgM and IgG antibody responses will be measured by ELISA against each antigen	week 15
Secondary	progression-free survival rate (cohort 2)	Will evaluate PFS rate at 1-year using Kaplan Meier methodology	1 year

External Links

•   Memorial Sloan Kettering Cancer Center