Pembrolizumab in Ultramutated and Hypermutated Endometrial Cancer (NCT02899793) | Clinical Trial Compass
CompletedPhase 2
Pembrolizumab in Ultramutated and Hypermutated Endometrial Cancer
United States25 participantsStarted 2016-09
Plain-language summary
Primary Objectives: To assess the antitumor activity (proportion of objective response by RECIST 1.1 criteria) of pembrolizumab with objective tumor response in patients with persistent, recurrent or metastatic endometrial cancer harboring an ultra-mutated or hyper-mutated (MMR gene-defective) phenotype identified by next generation sequencing (NGS) and comprehensive genomic profiling (CGP). To determine the nature and degree of toxicity of pembrolizumab as assessed by CTCAE in patients with persistent, recurrent or metastatic endometrial carcinoma. Secondary Objective(s): To estimate the duration of progression-free survival (PFS) and overall survival (OS).
Who can participate
Age range18 Years – 100 Years
SexFEMALE
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Inclusion criteria
✓. Patients must have histologically confirmed endometrial cancer that is recurrent or progressive following at least one prior chemotherapy regimen.
✓. Patients with the following histologic epithelial cell types are eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, clear cell carcinoma, undifferentiated carcinoma, mixed epithelial carcinoma, carcinosarcoma, and adenocarcinoma not otherwise specified (N.O.S.).
✓. Tumors must demonstrate ultramutation (POLE/POLD1-mutation) and/or hyper-mutation (due to MMR gene defect) in a representative primary or metastatic tumor site by next generation sequencing (NGS) and Comprehensive Genomic Profiling (CGP) testing, and/or standard PCR-based DNA microsatellite instability (MSI) and immunohistochemistry (IHC).
✓. All patients must have measurable disease by RECIST 1.1.
✓. Patients must have a ECOG performance status of 0 or 1.
✓. Women of childbearing potential must have a negative urine and serum pregnancy test within 72 hours prior to receiving first dose and must be willing to use contraceptive through 120 days of last dose of Pembrolizumab.
✓. Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy. Patients with ≥ Grade 2 neuropathy are eligible.
✓
What they're measuring
1
Frequency of Objective Tumor Response as Assessed by RECIST 1.1- Overall Response Rate (ORR)
Timeframe: 4 years
2
Toxicity Grade of Adverse Events as Assessed by CTCAE v4
. Patients may have received prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy. All radiation therapy must be completed at least 4 weeks prior to the first date of study therapy.
Exclusion criteria
✕. Patients who have had prior therapy with nivolumab, pembrolizumab or with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways.
✕. History of severe hypersensitivity reaction to any monoclonal antibody.
✕. Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure and unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
✕. Patients who are pregnant or nursing. The effects of pembrolizumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP should use an adequate method to avoid pregnancy for 23 weeks after the last dose of investigational drug. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IV/L or equivalent units of HCG) within 24 hours prior to the start of pembrolizumab. Women must not be breastfeeding.
✕. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile or have undergone definitive radiation) do not require contraception.
✕. Patients with known brain metastases or leptomeningeal metastases are excluded unless the following conditions are met: Metastases have been treated and there is no evidence of progression by CT scan or magnetic resonance imaging (MRI) prior to the first dose of pembrolizumab administration). There must also be no requirement for immunosuppressive doses of systemic corticosteroids (\>10 mg/day prednisone equivalents) for at least 1 week prior to study drug administration.
✕. Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Patients should be excluded if they have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection (e.g., HCV RNA \[qualitative\] is detected).
✕. Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as SLE, connective tissue diseases, scleroderma, inflammatory bowel disease (IRB), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patient with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.