A Phase I Study of WT1 or NY-ESO-1 OLP4 Vaccine and Nivolumab For the Treatment of Recurrent Ovarian Cancer

Status: complete

This phase I trial studies the side effects of nivolumab in combination with Wilms tumor 1 (WT1) vaccine or New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) protein overlapping long peptides (OLP4) vaccine in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent) at least twice and is now in remission. Vaccines made from WT1 and NY-ESO-1 peptides may help the body build an effective immune response to kill tumor cells. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of cancer. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a substance that helps make more white blood cells, especially granulocytes, macrophages, and cells that become platelets. It is a cytokine that is a type of hematopoietic (blood-forming) agent. Montanide and Poly-ICLC have been shown to increase the effect of vaccines on the immune system. Giving WT1 or NY-ESO-1 vaccine together with nivolumab may work better in treating ovarian, fallopian tube, or primary peritoneal cancer.

Inclusion Criteria

Pathologic diagnosis of ovarian, fallopian tube or primary peritoneal cancer confirmed by pathology review at Memorial Sloan Kettering (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 cancer antigen (CA)-125 within normal limits, examination and computed tomography (CT) or magnetic resonance imaging (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 87. 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
Karnofsky performance status >= 70%
Absolute neutrophil count >= 1000/mcL
Platelets > 50 K/mcL
Total bilirubin =< 1.5 mg/dl
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limits of normal
Creatinine =< 1.5mg/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 (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses > 10 mg 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

PRIMARY OBJECTIVE:

I. To assess the safety of repeated vaccination with concomitant WT1 analog peptides administered with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Montanide or NY-ESO-1 overlapping peptides (OLP) administered with Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (Poly-ICLC) and Montanide for a total of 6 vaccinations with nivolumab to patients with recurrent ovarian cancer in second or third clinical remission.

SECONDARY OBJECTIVES:

I. To characterize patients by IMPACT testing, progression-free survival, and results of detailed immune monitoring to see if particular associations can be identified.

II. To evaluate the immune response (immunoglobulin G [IgG] and immunoglobulin M [IgM] WT1 antibody, T-cell assays, and standard immune monitoring platform) induced by the WT1 analog peptide vaccine with GM-CSF and Montanide in combination with nivolumab in patients with recurrent ovarian cancer who are in second or greater clinical remission. (Cohort 1)

III. To estimate the 1-year progression-free survival rate in patients with recurrent ovarian cancer who are treated with the WT1 analog peptide vaccine with GM-CSF and Montanide in combination with nivolumab. (Cohort 1)

IV. To evaluate the immune response (IgG and IgM NY-ESO-1 antibody, T cell assays, and standard immune monitoring platform) induced by the NY-ESO-1 protein or overlapping long peptides (OLP4) vaccine with Poly-ICLC and Montanide in combination with nivolumab in patients with recurrent ovarian cancer who are in second or greater clinical remission. (Cohort 2)

V. To estimate the 1-year progression-free survival rate in patients with recurrent ovarian cancer who are treated with the NY-ESO-1 OLP4 vaccine with Poly-ICLC and Montanide in combination with nivolumab. (Cohort 2)

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT 1: Patients receive GM-CSF SC on days -2 and 0 prior to each WT1 analog peptide vaccine administration. Patients then receive WT1 analog peptide vaccine with Montanide ISA 51 VG SC on weeks 0, 2, 4, 6, 8, and 10, and nivolumab intravenously (IV) over 30 minutes on weeks 0, 2, 4, 6, 8, 10, and 12 in the absence of disease progression or unacceptable toxicity. Patients who do not have disease progression at week 15, may receive additional vaccines as maintenance therapy once every 2 months beginning at week 19 for up to 4 doses.

COHORT 2: Patients receive NY-ESO-1 OLP4 vaccine with Poly-ICLC and Montanide ISA 51 VG SC on weeks 0, 2, 4, 6, 8, and 10, and nivolumab IV over 30 minutes on weeks 0, 2, 4, 6, 8, 10, and 12 in the absence of disease progression or unacceptable toxicity. Patients who do not have disease progression at week 15, may receive additional vaccines as maintenance therapy once every 2 months beginning at week 19 for up to 4 doses.

After completion of study treatment, patients are followed up every 3 months for 1 year.

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A Phase I Study of WT1 or NY-ESO-1 OLP4 Vaccine and Nivolumab For the Treatment of Recurrent Ovarian Cancer

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