Nivolumab in Treating Patients with Metastatic or Recurrent Uterine Cancer

Status: Active

Description

This phase II trial studies how well nivolumab works in treating patients with uterine cancer that has spread to other places in the body or come back after a period of improvement. 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.

Eligibility Criteria

Inclusion Criteria

  • Histologically confirmed diagnosis of metastatic or recurrent uterine cancer (endometrial carcinoma, carcinosarcoma, clear cell carcinoma, leiomyosarcoma, undifferentiated sarcoma, high grade endometrial stromal sarcoma) by Memorial Sloan Kettering Cancer Center; carcinosarcomas, endometrioid and clear cell carcinomas that appears to have arisen in the ovary/fallopian tube or peritoneum are also eligible; recurrence should not be amenable to curative approaches such as surgical resection or chemoradiotherapy
  • Tumor is confirmed to be one of the following: * MSI-high, or * MMR-deficient, or * Hypermutated defined as >= 20 somatic mutations in the tumor by MSK-IMPACT
  • One or more prior lines of cytotoxic treatment for advanced disease (prior hormonal therapy is not considered to count as prior lines of therapy)
  • Measurable disease by RECIST 1.1 criteria
  • No known central nervous system (CNS) metastases
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • White blood cells (WBC) >= 2000/uL
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Platelets (PLT) >= 100,000/uL
  • Hemoglobin (HGB) >= 8 g/dL
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) or creatinine clearance of >= 40 mL/min by Cockcroft-Gault formula
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN
  • Total bilirubin =< 1.5 x ULN, except subjects with Gilbert’s syndrome who can have total bilirubin =< 3.0 mg/dL
  • Able to sign voluntary written informed consent
  • Available archival tumor tissue or patient is willing to undergo new biopsy
  • Premenopausal women of child bearing potential must have a normal urine or serum beta-human chorionic gonadotropin (HCG) prior to enrollment, and must agree to use effective contraception during treatment with nivolumab and for at least 5 months following the last dose of nivolumab

Exclusion Criteria

  • Disease eligible for potentially curative treatment with standard chemotherapy, surgical resection, or chemoradiotherapy
  • Known or suspected autoimmune disease, except for subjects with vitiligo, diabetes mellitus, resolved childhood asthma/atopy, residual hypothyroidism due to an autoimmune immune condition only requiring thyroid hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  • Serious uncontrolled medical disorder or active infection which would impair the ability of the subject to receive protocol therapy or whose control would be jeopardized by protocol therapy
  • History of bowel obstruction, refractory ascites, or bowel perforation due to advanced disease within the past 3 months from start of study treatment
  • Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways
  • Patients who have a condition that requires systemic treatment with either corticosteroids within 7 days of enrollment (systemic corticosteroid therapy is defined as > 10 mg daily prednisone or its equivalent); or who require 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
  • Prior history of malignancy or a concurrent malignancy, with the exception of cutaneous basal cell carcinoma or squamous cell carcinoma, superficial bladder cancer, or in situ carcinoma of the uterine cervix, prostate, or breast, unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated to be required during the study period
  • Breastfeeding women, pregnant women
  • Prisoners or subjects who are involuntarily incarcerated
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
  • Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (hepatitis C virus [HCV] antibody) indicating acute or chronic infection (if patient has documented hepatitis B and C from within 6 months of enrollment, these tests do not need to be repeated)
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Known allergy or adverse drug reaction to nivolumab, or a history of allergy to study drug components

Locations & Contacts

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Claire F. Friedman
Phone: 646-888-4221
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Claire F. Friedman
Phone: 646-888-4221
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Claire F. Friedman
Phone: 646-888-4221

New York

Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Claire F. Friedman
Phone: 646-888-4221
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Claire F. Friedman
Phone: 646-888-4221
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Claire F. Friedman
Phone: 646-888-4221
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Claire F. Friedman
Phone: 646-888-4221

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To define the progression-free survival rate at 24 weeks in patients with microsatellite instability (MSI)-high, mismatch repair deficient (MMR-D), or hypermutated persistent or recurrent uterine cancer treated with single-agent nivolumab.

II. To define the proportion of patients who have objective tumor response (complete or partial) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in patients with MSI-high, MMR-D, or hypermutated persistent or recurrent uterine cancer treated with single-agent nivolumab.

SECONDARY OBJECTIVES:

I. To determine the progression-free survival rate by RECIST 1.1 and overall survival in this population of recurrent uterine cancer patients treated with nivolumab.

II. To determine the frequency and severity of adverse events associated with treatment with nivolumab as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

III. To determine the duration of response and duration of disease control.

EXPLORATORY OBJECTIVES:

I. Correlate the somatic mutational burden with clinical benefit from nivolumab, both overall response rate (ORR) and progression-free survival (PFS) rate at 24 weeks.

II. Correlate the somatic mutational burden identified by Memorial Sloan Kettering (MSK)-IMPACT with the MSIsensor algorithm score.

III. Correlate the MSIsensor score with the MMR immunohistochemistry (IHC) status (immunohistochemical staining for mismatch repair enzyme proteins).

IV. Correlate the pre-treatment immune phenotype (tumor infiltrating lymphocyte and PD-L1 status) with best overall response rate (ORR) and progression free survival rate at 24 weeks.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for at least 2 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Claire F. Friedman

Trial IDs

Primary ID 17-180
Secondary IDs NCI-2017-01524
Clinicaltrials.gov ID NCT03241745