Testing the Response to the Anti-cancer Drug, Triapine, in Uterine Cancers Using Markers From the Tissue at the Time of Hysterectomy

NCT04494113 | Active Not Recruiting Early Phase 1 FDA Drug

• 3 other identifiers: NCI-2020-0545710401UM1CA186691
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Endometrial Serous Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 6-8 hours post-triapine infusion

Secondary Outcomes (2)

• Incidence of adverse events

  Up to day 42

• Pharmacokinetic (PK) analysis

  Baseline, 5 minutes before end of triapine infusion, 6-8 hours post-infusion (at time of surgical tissue resection), and 24 hours post-infusion

Other Outcomes (2)

• Single-cell transcriptome analysis

  Baseline, post-triapine infusion, surgical resection

• Whole exome sequencing (WES) analysis

  Baseline

Study Arms (1)

Treatment (triapine, surgical resection)

EXPERIMENTAL

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Resection; Drug: Triapine

Interventions

Triapine DRUG

Given IV

Also known as: 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, 3-AP, 3-Apct, OCX-0191, OCX-191, OCX191, PAN-811

Treatment (triapine, surgical resection)

Biospecimen Collection PROCEDURE

Undergo collection of tissue and blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (triapine, surgical resection)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Treatment (triapine, surgical resection)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (triapine, surgical resection)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed uterine corpus serous adenocarcinoma
• Patients must be planned for surgical hysterectomy and operative staging
• Patients must have adequate archival tissue obtained within 8 weeks of step 1 registration OR have sufficient tumor tissue and be willing to undergo an endometrial pipelle biopsy prior to beginning study treatment.
• Patients must have adequate primary tumor volume, as determined by imaging (e.g., computed tomography \[CT\], ultrasound, magnetic resonance imaging \[MRI\]) at eligibility screening, to accommodate research specimen collections in addition to clinical pathology evaluation
• Patients must not have received any prior anticancer treatment for endometrial cancer
• Patients must be \>= 18 years old. Because no dosing or adverse event data are currently available on the use of triapine in patients \< 18 years of age, children are excluded from this study
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Absolute neutrophil count \>= 1,000/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9.0 g/dL
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
• International normalized ratio (INR) =\< 2
• Creatinine =\< 1.5 x institutional ULN OR glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m\^2
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
• Patients who are receiving any other investigational agents
• Patients who have known brain metastases, as they are not candidates for surgery
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine
• Patients receiving any medications or substances that are inhibitors or inducers of triapine, as well as medications known to be associated with methemoglobinemia, are ineligible. Triapine drug interactions have not yet been identified. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Patients with uncontrolled intercurrent illness
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are not eligible. Patients at risk for G6PD deficiency must be screened prior to enrollment

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

Location

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Interventions

Biopsy; Specimen Handling; 3-aminopyridine-2-carboxaldehyde thiosemicarbazone

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Rebecca L Stone

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2020
• First Posted: July 31, 2020
• Study Start: February 8, 2022
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

US (7)