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

NCT02737787 | Completed Phase 1

• 1 other identifier: 15-247
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Ovarian Cancer; Fallopian Tube; Primary Peritoneal Cancer; Recurrent Ovarian Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• immune response (cohort 2)

  week 15

• progression-free survival rate (cohort 2)

  1 year

Study Arms (2)

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.

Biological: WT1 Vaccine; Drug: Nivolumab

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.

Drug: Nivolumab; Biological: NY-ESO-1 Vaccine

Interventions

WT1 Vaccine BIOLOGICAL

WT1 Vaccine and Nivolumab

Nivolumab DRUG

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

ESO-1 Vaccine and Nivolumab; WT1 Vaccine and Nivolumab

NY-ESO-1 Vaccine BIOLOGICAL

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.

ESO-1 Vaccine and Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (All Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (All protocol activities)

Rockville Centre, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Ovarian Neoplasms; Neoplasm Metastasis

Interventions

Nivolumab; NY-ESO-1-APH vaccine

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Roisin O'Cearbhaill, MB BCh BAO

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open-label, non-randomized phase I trial of a vaccine combined with anti-PD-1 (nivolumab) in patients with recurrent ovarian cancer who are in second or third clinical remission following additional chemotherapy.

Study Record Dates

• First Submitted: April 5, 2016
• First Posted: April 14, 2016
• Study Start: April 1, 2016
• Primary Completion: April 6, 2023
• Study Completion: April 6, 2023
• Last Updated: April 7, 2023

Record last verified: 2023-04

Locations

US (7)