Triapine for Uterine Cancer

Not currently recruiting at 7 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Triapine inhibitors, Methemoglobinemia drugs

Disqualifiers: Chemotherapy, Radiotherapy, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests triapine, a new drug, to determine if it can slow uterine cancer growth by blocking enzymes that aid cancer cell growth. Researchers will administer triapine to patients before surgery to remove the uterus and other organs. They aim to discover if adding triapine to the usual surgery and chemotherapy (with or without radiation) is more effective than the current method alone. Individuals with uterine corpus serous adenocarcinoma, who are scheduled for surgery and have not yet started treatment, may be suitable candidates for this trial. As an Early Phase 1 trial, this research focuses on understanding how triapine works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take medications that are inhibitors or inducers of triapine, or those associated with methemoglobinemia. You will be counseled on potential drug interactions during the enrollment process.

Is there any evidence suggesting that triapine is likely to be safe for humans?

Research has shown that triapine has been tested in patients with various types of cancer to assess its safety and effectiveness. Most patients have tolerated triapine well, though some have experienced side effects such as nausea or tiredness. In certain studies, researchers sought to determine the highest dose that could be taken without serious issues.

Triapine has also been compared to other cancer treatments and has shown promise in slowing tumor growth. As this is an early phase trial, the treatment is still being carefully evaluated for safety. However, past studies suggest that triapine might be a safe option for some patients. Participants should discuss possible risks with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Triapine is unique because it targets a specific enzyme, ribonucleotide reductase, which is crucial for DNA synthesis in cancer cells. Unlike the standard treatments for uterine cancer, such as surgery, radiation, and chemotherapy, Triapine disrupts the cancer cells' ability to replicate their DNA, potentially halting tumor growth. Researchers are excited about Triapine because it offers a novel mechanism of action that could enhance the effectiveness of surgical resection, possibly leading to improved outcomes for patients with uterine cancer.

What evidence suggests that triapine might be an effective treatment for uterine cancer?

Research has shown that Triapine might stop cancer cells from growing by blocking an essential enzyme. Some studies suggest that Triapine alone may not be very effective because it doesn't remain in the body long. However, when combined with treatments like chemotherapy or radiation, it might work better. Early tests in various cancers indicate that Triapine can enhance these treatments. In this trial, participants will receive Triapine followed by surgical resection to evaluate its effectiveness specifically for uterine cancer. More research is needed to determine its efficacy in this context. ^{2 3 4 5 6}

Who Is on the Research Team?

Rebecca L Stone

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with specific types of uterine cancer who are planning to have a hysterectomy and haven't had previous cancer treatment. They must be in good health overall, with proper kidney, liver, and blood cell function. People with certain heart conditions or infections like hepatitis B or C need to have them under control. Pregnant women can't join, and participants should understand the study well enough to consent.

Inclusion Criteria

I have not had any previous cancer treatment for endometrial cancer.

Platelets >= 100,000/mcL

My cancer is a specific type of uterine cancer called serous adenocarcinoma.

Exclusion Criteria

I do not have any unmanaged ongoing illnesses.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine

Patients with psychiatric illness/social situations that would limit compliance with study requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive triapine IV over 2 hours on day 1, followed by surgical resection and tissue collection 6-8 hours after the initiation of the triapine infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pharmacokinetic analysis and adverse event monitoring

Up to 42 days

What Are the Treatments Tested in This Trial?

Interventions

• Triapine

Trial Overview The trial is testing Triapine's effectiveness when added to standard surgery followed by chemotherapy or radiation therapy for uterine cancers. Researchers will look at tissue markers from samples collected during surgery to see how the tumor cells respond.

How Is the Trial Designed?

Group I: Treatment (triapine, surgical resection) Experimental Treatment 4 Interventions

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase I trial involving 21 patients with advanced cancer, the recommended phase II dose of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) was determined to be 120 mg/m²/day administered via a 96-hour intravenous infusion every 2 weeks, with manageable dose-limiting toxicities such as neutropenia and hyperbilirubinemia.

While there were no objective responses to treatment, some patients experienced prolonged disease stabilization and decreases in serum tumor markers, indicating potential efficacy in managing advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic study of the ribonucleotide reductase inhibitor, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, administered by 96-hour intravenous continuous infusion. Wadler, S., Makower, D., Clairmont, C., et al.[2007]

In a study of 24 patients with advanced-stage cervical cancer, triapine combined with cisplatin and radiation therapy demonstrated a low 3-year pelvic locoregional relapse rate of 4%, indicating its potential effectiveness in treatment.

The treatment resulted in high disease-free survival (80%) and overall survival (82%) rates over a median follow-up of 3.4 years, suggesting that triapine is a safe and promising option for patients with untreated cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Disease Control with Triapine-Based Radiochemotherapy for Patients with Stage IB2-IIIB Cervical Cancer. Kunos, CA., Sherertz, TM.[2021]

Three new thiosemicarbazones (TSCs) were developed as triapine analogues, showing promising redox activity and stability at physiological pH, which could enhance their therapeutic potential.

Copper(II) complexes derived from these TSCs demonstrated significant antiproliferative effects against cancer cell lines, with one complex showing selectivity for cancer cells over normal cells, indicating potential for targeted cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triapine Analogues and Their Copper(II) Complexes: Synthesis, Characterization, Solution Speciation, Redox Activity, Cytotoxicity, and mR2 RNR Inhibition. Besleaga, I., Stepanenko, I., Petrasheuskaya, TV., et al.[2021]

Triapine effectively reduces the viability of epithelial ovarian cancer (EOC) cells in a dose- and time-dependent manner, inducing apoptosis through mechanisms involving the mitochondrial pathway, as indicated by Bid activation and other apoptotic markers.

Triapine enhances the cytotoxic effects of standard chemotherapy drugs carboplatin and paclitaxel, suggesting its potential as a valuable addition to combination therapies for treating ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) induces apoptosis in ovarian cancer cells. Alvero, AB., Chen, W., Sartorelli, AC., et al.[2015]

Triapine, a ribonucleotide reductase inhibitor, is being evaluated for treating cervical and vulvar cancer in combination with cisplatin chemoradiation, and researchers are exploring its oral administration to simplify treatment logistics.

A validated LC-MS/MS assay was developed to accurately quantify triapine in human plasma, which will help assess its pharmacokinetics and oral bioavailability, ensuring the method meets FDA standards for bioanalytical validation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LC-MS/MS assay for the quantitation of the ribonucleotide reductase inhibitor triapine in human plasma. Matsumoto, J., Kiesel, BF., Parise, RA., et al.[2018]

The study successfully developed liposomal formulations of copper(II) complexes of triapine, which showed improved encapsulation efficacy and slower drug release compared to free triapine, addressing its short plasma half-life.

In vitro and in vivo studies demonstrated that liposomal Cu-triapine significantly reduced cytotoxicity and DNA damage while achieving higher copper plasma levels, suggesting enhanced tumor targeting and potential efficacy as an anticancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal formulations of anticancer copper(II) thiosemicarbazone complexes. Mathuber, M., Hager, S., Keppler, BK., et al.[2022]

Citations

1. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04494113/

Clinical Trial: NCT04494113 This early phase I trial investigates the response of the anti-cancer drug, triapine, in uterine cancers by using markers from tissue samples.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006295299004190

Triapine (3-aminopyridine-2-carboxaldehyde ... We now report additional preclinical data which suggest that pharmacokinetic measurements of Triapine's inhibition of RR activity in cancer cells can be useful ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3288125/

A phase I and pharmacokinetic study of oral 3 ... This study was designed to estimate the maximum-tolerated dose (MTD) and oral bioavailability of 3-AP in patients with advanced stage solid tumors.

4. withpower.com withpower.com/trial/early-phase-1-adenocarcinoma-10-2020-c6fec

Triapine for Uterine Cancer · Info for Participants However, some studies suggest that Triapine alone may not be very effective against solid tumors due to its short time in the body and quick breakdown.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02595879

Triapine With Chemotherapy and Radiation Therapy in ... Triapine may stop the growth of cancer cells by blocking an enzyme needed for cell growth. Cisplatin is a drug used in chemotherapy that kills cancer cells by ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04494113

NCT04494113 | Testing the Response to the Anti-cancer ... 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 ...