Triapine for Uterine Cancer

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen by Rebecca L Stone

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the idea that Triapine for Uterine Cancer is an effective treatment?

The available research shows that Triapine has been studied for its effectiveness in treating cervical cancer, which is similar to uterine cancer. In clinical trials, Triapine was combined with another drug, cisplatin, and radiation therapy, and it helped control the disease over a long period. 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. Researchers are exploring ways to improve its effectiveness, such as using special carriers to deliver the drug more efficiently. While there is promising data for cervical cancer, specific data for uterine cancer is not provided in the available research. ^{1 2 3 4 5}

What safety data is available for Triapine in treating cancer?

Triapine, also known as 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, has been evaluated in several clinical trials for its safety and efficacy. A Phase I trial identified dose-limiting toxicities and the maximum-tolerated dose for a 96-hour intravenous infusion in patients with advanced cancer. Additionally, Triapine has been studied in combination with cisplatin radiochemotherapy for cervical cancer, showing long-term disease control. However, challenges such as short plasma half-life and fast metabolism have been noted, leading to research into liposomal formulations to improve its pharmacokinetic properties. Overall, Triapine has been shown to enhance radiochemosensitivity and induce apoptosis in cancer cells, but further studies are needed to optimize its delivery and efficacy. ^{1 2 3 4 6}

Is the drug Triapine a promising treatment for uterine cancer?

Triapine is a promising drug because it helps make cancer treatments more effective by slowing down the repair of cancer cells' DNA. This can lead to better control of the disease and improve survival rates in patients with certain types of cancer. ^{1 2 3 4 5}

Research Team

Rebecca L Stone

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Eligibility Criteria

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

Treatment Details

Interventions

• Triapine (Ribonucleotide Reductase Inhibitor)

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.

Participant Groups

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+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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]

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]

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]

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]

References

1. United States 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. [2007]

2. England pubmed.ncbi.nlm.nih.gov

LC-MS/MS assay for the quantitation of the ribonucleotide reductase inhibitor triapine in human plasma. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Liposomal formulations of anticancer copper(II) thiosemicarbazone complexes. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Triapine Analogues and Their Copper(II) Complexes: Synthesis, Characterization, Solution Speciation, Redox Activity, Cytotoxicity, and mR2 RNR Inhibition. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) induces apoptosis in ovarian cancer cells. [2015]