This early phase I trial investigates the response to the anti-cancer drug, triapine, in uterine cancers by using markers from tissue samples at the time of removal of the uterus, ovaries, and fallopian tubes (hysterectomy and bilateral salpingo-oophorectomy). Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Adding triapine to the usual approach of surgery followed by chemotherapy alone or in combination with radiation therapy may help to slow the growth of uterine cancer.
PRIMARY OBJECTIVE: I. Determine whether intravenous (IV) triapine 25 mg/m\^2 will induce cell cycle arrest as measured by phospho-histone H3 (pHH3) in uterine serous adenocarcinoma cells removed at the time of hysterectomy. SECONDARY OBJECTIVES: I. Determine whether a preoperative dose of intravenous triapine 25 mg/m\^2 can be safely given prior to hysterectomy and staging for uterine serous adenocarcinoma. II. Determine whether changes in cyclin D/E and Ki-67 protein expression are detectable using immunohistochemistry pre- and post-triapine treatment in uterine serous adenocarcinomas. III. Evaluate plasma and tissue triapine concentrations. EXPLORATORY OBJECTIVES: I. Determine the feasibility of using single-cell transcriptome analysis to quantify changes in gene expression following triapine treatment and to evaluate their concordance with immunohistochemistry (IHC) endpoints of cell cycle arrest. II. Identify genomic variants of uterine serous adenocarcinoma (including but not limited to p53) with treatment response to ribonucleotide reductase inhibitors such as triapine using whole exome sequencing (WES). OUTLINE: Patients receive triapine IV over 2 hours on day 1. Patients then undergo surgical resection and tissue collection 6-8 hours after the initiation of the triapine infusion. Patients also undergo biopsy and collection of blood samples on study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Undergo biopsy
Undergo collection of tissue and blood samples
Undergo surgical resection
Given IV
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Pharmacodynamic response
Pharmacodynamic response rate will be estimated as the proportion of evaluable patients who achieve pharmacodynamic response defined as a decrease in phospho-histone H3 immunoscore of \>= 1 from baseline to post-exposure of intravenous triapine for each patient. The corresponding 95% confidence interval will be provided.
Time frame: Up to 6-8 hours post-triapine infusion
Incidence of adverse events
Dose-limiting toxicities, as listed by Common Terminology Criteria for Adverse Events, version 5, are defined as any pre-surgical grade 3 or higher non-hematologic toxicity or grade 4 neutropenia, neutropenic fever, or thrombocytopenia within 24 hours of triapine administration. Toxicity will be tabulated by type and grade.
Time frame: Up to day 42
Pharmacokinetic (PK) analysis
End of infusion plasma concentrations represent maximum concentration and will be compared with historical data. Post-triapine plasma and tissue concentrations will generate plasma to tissue ratios, which represent the tissue partitioning coefficient, a useful PK parameter.
Time frame: Baseline, 5 minutes before end of triapine infusion, 6-8 hours post-infusion (at time of surgical tissue resection), and 24 hours post-infusion
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