| Eligibility |
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: 1. MSI-high, or 2. MMR-deficient, or 3.
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 CNS metastases
- ECOG Performance status 0-1
- ECOG Performance status 0-1
- WBC = 2000/uL, ANC = 1500/uL, PLT = 100,000/uL, HGB = 8 g/dL
- Serum creatinine = 1.5 x ULN or creatinine clearance of = 40mL/min by Cockroft-Gault
formula
- AST (SGOT) and ALT (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
- Female, 18 years of age or older
- 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-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 (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.
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