A Phase 1 Adaptive Dose Escalation with Dose Expansion Study of Triapine in Combination with Temozolomide (TMZ) for Patients with Recurrent Glioblastoma

This phase I trial tests the safety, side effects, and best dose of triapine in combination with temozolomide in treating patients with glioblastoma that has come back after a period of improvement (recurrent). Triapine inhibits an enzyme responsible for producing molecules required for the production of deoxyribonucleic acid (DNA), which may inhibit tumor cell growth. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Giving triapine in combination with temozolomide may be safe, tolerable, and/or effective in treating patients with recurrent glioblastoma.

Start Date23 Jul 2024

Sponsor / Collaborator

Northwestern University

[+2]

NCT05724108

/ RecruitingPhase 2IIT

A Phase II Randomized Control Trial of Triapine Plus Lutetium Lu 177 Dotatate Versus Lutetium Lu 177 Dotatate Alone for Well-Differentiated Somatostatin Receptor-Positive Neuroendocrine Tumors

This phase II trial compares the effect of adding triapine to lutetium Lu 177 dotatate versus lutetium Lu 177 dotatate alone (standard therapy) in shrinking tumors or slowing tumor growth in patients with neuroendocrine tumors that have spread from where they first started (primary site) to other places in the body (metastatic). Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for deoxyribonucleic acid synthesis and cell growth. Lutetium Lu 177 dotatate is a radioactive drug. It binds to a protein called somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu 177 dotatate builds up in these cells and gives off radiation that may kill them. It is a type of radioconjugate and a type of somatostatin analog. Giving triapine in combination with lutetium Lu 177 dotatate may be more effective at shrinking tumors or slowing tumor growth in patients with metastatic neuroendocrine tumors than the standard therapy of lutetium Lu 177 dotatate alone.

Start Date30 Aug 2023

Sponsor / Collaborator

National Cancer Institute

NCT04494113

/ SuspendedEarly Phase 1IIT

A Phase 0 Window-of-Opportunity Pharmacodynamic Trial of Triapine (NSC# 663249) in Uterine Corpus Serous Adenocarcinoma

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.

Start Date08 Feb 2022

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Triapine

100 Translational Medicine associated with Triapine

100 Patents (Medical) associated with Triapine

321

Literatures (Medical) associated with Triapine

01 Dec 2025·Cancer Chemotherapy and Pharmacology

Dose finding, bioavailability, and PK-PD of oral triapine with concurrent chemoradiation for locally advanced cervical cancer and vaginal cancer (ETCTN 9892)

Article

Author: Richardson, Debra L ; Mahdi, Haider ; Kunos, Charles ; Behr, Sarah ; Cooper, Kristine L ; Ivy, S Percy ; Vargo, John ; Huang, Marilyn ; Chauhan, Aman ; Orr, Brian ; Chu, Edward ; Kohn, Elise C ; Olawaiye, Alexander B ; Ueland, Frederick ; Girda, Eugenia ; Christner, Susan M ; Sullivan, Stephanie A ; Taylor, Sarah E ; Lin, Yan ; Courtney-Brooks, Madeleine ; Beriwal, Sushil ; Beumer, Jan H ; Gallion, Holly ; Fabian, Denise ; Randall, Leslie M

BACKGROUNDThe addition of IV triapine to chemoradiation appeared active in phase I and II studies but drug delivery is cumbersome. We examined PO triapine with cisplatin chemoradiation.METHODSWe implemented a 3 + 3 design for PO triapine dose escalation with expansion, starting at 100 mg, five days a week for five weeks while receiving radiation with weekly IV cisplatin for locally advanced cervical or vaginal cancer. Maximum tolerated dose (MTD), dose limiting toxicity (DLT), adverse events, pharmacokinetics (PK), pharmacodynamics (PD), and metabolic complete response (mCR) were assessed.RESULTS19/21 patients were DLT evaluable. DLTs included grade 4 neutropenia (n = 2), leukopenia (n = 2), lymphopenia (n = 2), and hypokalemia (n = 1). Grade 3 toxicities at least possibly related were as expected for cisplatin chemoradiation: lymphopenia (n = 12), anemia (n = 10), neutropenia (n = 4), leukopenia (n = 8), decreased platelets (n = 2), hypertension (n = 1), and hyponatremia (n = 1). MTD and RP2D were established at 100 mg. 8/13 evaluable patients had a mCR. Triapine had a bioavailability of 59%. Methemoglobin levels correlated with triapine exposure. Smoking almost doubled CYP1A2 mediated triapine clearance.CONCLUSIONSOral triapine is safe when given with cisplatin chemoradiation, convenient, bioavailable. Exposure is negatively impacted by smoking, and methemoglobin is a biomarker of exposure.CLINICAL TRIAL REGISTRATIONNCT02595879.

01 Feb 2025·Toxicology

Opposing effects of mycotoxins alternariol and deoxynivalenol on the immunomodulatory effects of oxaliplatin and triapine

Article

Author: Gufler, Judith ; Heffeter, Petra ; Marko, Doris ; Kowol, Christian R ; Hager, Sonja

Mycotoxin occurrence in food worldwide is estimated to increase due to climate change. Moreover, studies on how these food contaminants interfere with medications and especially anticancer therapies are rare. With the rise of anticancer immunotherapies, particularly mycotoxins with immunomodulatory activity, such as alternariol (AOH) or deoxynivalenol (DON), are of great concern. Both mycotoxins interfere with the pro-inflammatory nuclear factor kappa B (NF-κB) pathway in myeloid cells. This pathway not only plays an important role in the anticancer immune response but also inflammatory side effects induced by chemotherapeutic drugs. Consequently, the aim of this study was to investigate possible beneficial or detrimental immunomodulatory interactions between these mycotoxins and anticancer drugs. To assess the combined influence of mycotoxins and anticancer therapies on immune cell stimulation, THP-1 NF-κB reporter cells were utilized as monocytes as well as differentiated and polarized macrophages. Parameters for activation (NF-κB activity and protein expression), differentiation (CD14 and CD71 surface marker expression) and polarization (interleukin 10 (IL10), interleukin 8 (CXCL8), tumor necrosis factor α (TNF), prostaglandin-endoperoxide synthase 2 expression and CXCL8 secretion) were assessed upon combinatory treatment. Both mycotoxins affected the immunostimulatory effects of the pre-selected anticancer drugs oxaliplatin and triapine, although in opposing directions. While AOH generally suppressed a drug-induced activation and increased anti-inflammatory IL10 levels, DON potentiated activation and pro-inflammatory markers, such as CXCL8 and TNF in immune cells. In conclusion, AOH and DON have the potential to alter the immunological effects of anticancer therapies, which should be considered during therapy as well as in their future risk assessment.

23 Dec 2024·JACS Au

DefNEtTrp: An Iron Dual Chelator Approach for Anticancer Application

Article

Author: Nieves-Escobar, Christopher ; Rodríguez, Israel ; Soto-Millán, Alexandra M. ; Strangmark, Estelle ; Tinoco, Arthur D. ; Acosta, Carmen ; Claudio-Ares, Oscar ; M. Orta-Rivera, Aixa ; Astashkin, Andrei V. ; Vargas Figueroa, Adriana I.

Targeting iron metabolism has emerged as a novel therapeutic strategy for the treatment of cancer. As such, iron chelator drugs are repurposed or specifically designed as anticancer agents. Two important chelators, deferasirox (Def) and triapine (Trp), attack the intracellular supply of iron (Fe) and inhibit Fe-dependent pathways responsible for cellular proliferation and metastasis. Trp, in particular, forms a redox active ferrous complex that inactivates the Fe-dependent ribonucleotide reductase (RNR), responsible for DNA replication. Building on recent efforts to employ intracellular Fe chelation for anticancer therapy, this work aimed to develop the Fe dual chelator ligand DefNEtTrp, consisting of the Def and Trp moieties, to exploit their high affinity Fe(II/III) binding and redox modulation. Using UV-vis spectroscopy, EPR spectroscopy, ESI and MALDI-TOF mass spectrometry, and cyclic voltammetry analyses, DefNEtTrp is shown to retain its Fe binding at both chelator moieties and generate a redox active Fe(III) complex Fe₃(DefNEtTrp)₂ featuring a reduction potential (E _1/2 = +0.103 V vs normal hydrogen electrode) within the biological window. Screened against different cancer cell line types, DefNEtTrp exhibits potent and broad-spectrum antiproliferative and cell death behavior. Its cytotoxicity (IC₅₀ 0.77 ± 0.06 μM) is superior to that of unconjugated Def and Trp ligands (IC₅₀ 2.6 ± 0.15 μM and 1.1 ± 0.04 μM, respectively) in single-compound and combination treatments and is selective toward cancer cells. The cell death mechanism of the dual chelator is assessed in the context of intracellular labile Fe binding and was found to induce both apoptosis and ferroptosis.

News (Medical) associated with Triapine

14 May 2024

·www.prnewswire.com

Nanopharmaceutics and Northwestern University Announce Initiation of Phase I Adaptive Dose Escalation Clinical Study with Dose Expansion of Oral Triapine® in Combination with Temozolomide (TMZ) for Patients with Recurrent Glioblastoma

ALACHUA, Fla. and CHICAGO, May 14, 2024 /PRNewswire/ -- Nanopharmaceutics, Inc. (OTC:TGRP), a clinical-stage pharmaceutical development company, announced the initiation of a Phase I clinical study with the Robert H. Lurie Comprehensive Cancer Center of Northwestern University "A Phase 1 Adaptive Dose Escalation With Dose Expansion Study of Triapine in Combination With Temozolomide (TMZ) for Patients With Recurrent Glioblastoma" (ClinicalTrials.gov Identifier: NCT06410248). The primary objective of this phase 1 study will be to determine the recommended phase 2 dose (RP2D) for Triapine® in combination with temozolomide (TMZ). Secondary objectives include evaluation of the safety profile of Triapine® in combination with temozolomide (TMZ), progression-free survival (PFS), overall survival (OS), overall response rate (ORR) per RANO criteria, and quality of life per FACT-Br. The study will recruit 40-45 patients with an established diagnosis of recurrent glioblastoma, and there will be an exploratory arm to investigate drug delivery into brain tumor tissue and target engagement in a cohort who are surgical candidates for re-resection of recurrent glioblastoma. Funding for the study is provided by BrainUp. Oral Triapine® has been shown to be safe, tolerable, and convenient in multiple clinical studies. Ribonucleotide Reductase (RNR) Regulatory Subunit 2 (RRM2) targeting with Triapine® may overcome chemoresistance and improve the clinical efficacy of TMZ therapy. Preliminary research from Dr. Atique Ahmed's lab at Northwestern University has uncovered a critical factor that helps glioblastoma, an aggressive brain cancer, resist chemotherapy treatment. About the Robert H. Lurie Comprehensive Cancer Center of Northwestern University The Robert H. Lurie Comprehensive Cancer Center of Northwestern University is a National Cancer Institute-designated Comprehensive Cancer Center located on Northwestern Memorial Hospital's downtown medical campus in the Streeterville neighborhood of Chicago, Illinois, United States. About BrainUp BrainUp is a nonprofit founded by Dan & Meg Kresach of Frankfort, Illinois. They founded BrainUp after their only child Olivia, was diagnosed 10 years ago with a Glioblastoma at the age of 22 years old. She died on April 19, 2014. The Kresachs formed BrainUp to fund brain cancer research. They have an annual run/walk to raise money for brain cancer research. They have funded over 1.2 million dollars supporting brain cancer research and trials at Chicago healthcare institutions. BrainUp is the financial supporter of Karan Dixit, M.D. (PI) and Atique Ahmed, Ph.D of Northwestern University Chicago, Illinois. To learn more about BrainUp, visit brainup.ngo About Nanopharmaceutics, Inc. Nanopharmaceutics, Inc. is a clinical-stage specialty pharmaceutical company developing oral, topical, and injectable products for cancer, central nervous system (CNS) disorders, and infectious diseases. Leveraging its expertise in nanoparticle and fine-particle formulations, which can specifically be used to improve hard-to-deliver BCS category II and IV drugs, Nanopharmaceutics is focused on formulation development aimed at improving drug absorption and stability. Contact: Nanopharmaceutics, Inc. (OTC: TGRP) James D. Talton, Ph.D. President and Chief Executive Officer 386-401-6304 SOURCE Nanopharmaceutics, Inc.

Phase 1Oligonucleotide

02 Nov 2022

·www.prnewswire.com

Nanopharmaceutics, Inc. Announces the End of Patient Recruitment for the National Cancer Institute (NCI) Sponsored Phase 3 Clinical Study in Advanced-Stage Cervical and Vaginal Cancers with Cisplatin During Radiation Therapy with and without Triapine®

ALACHUA, Fla., Nov. 2, 2022 /PRNewswire/ -- Nanopharmaceutics, Inc., a clinical-stage pharmaceutical development company, today announced completion of patient enrollment in the 450 patient Phase 3 clinical study sponsored by the NCI, part of the National Institutes of Health, and led by NCI funded network group, NRG Oncology, with participation of the NCI National Clinical Trials Network (NCTN), "A Randomized Phase III Trial of Radiation Therapy and Cisplatin Alone or in Combination with Intravenous Triapine in Women with Newly Diagnosed Bulky Stage IB2, Stage II, IIIB, or IVA Cancer of the Uterine Cervix or Stage II-IVA Vaginal," (NRG-GY006, ClinicalTrials.gov Identifier: NCT02466971). The randomized phase 3 trial is evaluating radiation therapy and cisplatin with Nanopharmaceutics' proprietary formulation of Triapine® compared to the standard radiation therapy and cisplatin, alone, in treating patients with newly diagnosed stage IB2, II, or IIIB-IVA cervical cancer or stage II-IVA vaginal cancer. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, stopping them from dividing, or by stopping them from spreading. Triapine® may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether radiation therapy and cisplatin are more effective with Triapine® Injection in treating cervical or vaginal cancer. 450 patients were enrolled in the study, which was performed under a Cooperative Research and Development Agreement (CRADA) between NCI and Nanopharmaceutics. About Triapine® Triapine® is a synthetic heterocyclic carboxaldehyde thiosemicarbazone with potential antineoplastic activity being studied in the treatment of cancer. It is a type of ribonucleotide reductase inhibitor. Also called 3-aminopyridine-2-carboxaldehyde thiosemicarbazone and 3-AP, Triapine® inhibits the enzyme ribonucleotide reductase, resulting in the inhibition of the conversion of ribonucleoside diphosphates to deoxyribonucleotides necessary for DNA synthesis. About Nanopharmaceutics, Inc. Nanopharmaceutics, Inc. is a clinical-stage specialty pharmaceutical company developing oral, topical, and injectable products for cancer, central nervous system (CNS) disorders, and infectious diseases. Leveraging its expertise in nanoparticle and fine-particle formulations, which can specifically be used to improve hard-to-deliver Biopharmaceutics Classification System (BCS) category II and IV drugs, Nanopharmaceutics is focused on formulation development aimed at improving drug absorption and stability. Contact: Nanopharmaceutics, Inc. James D. Talton, Ph.D. President and Chief Executive Officer 352-401-6304 [email protected] SOURCE Nanopharmaceutics, Inc.

Radiation Therapy

02 Nov 2022

·www.biospace.com

Nanopharmaceutics, Inc. Announces the End of Patient Recruitment for the NCI Sponsored Phase 3 Clinical Study in Advanced-Stage Cervical and Vaginal Cancers with Cisplatin During Radiation Therapy with and without Triapine®

Radiation Therapy

100 Deals associated with Triapine

External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Adenosquamous Carcinoma	Phase 3	US	National Cancer Institute	10 May 2016
Cervical Squamous Cell Carcinoma	Phase 3	CA	National Cancer Institute	10 May 2016
Cervical Squamous Cell Carcinoma	Phase 3	PR	National Cancer Institute	10 May 2016
Cervical Squamous Cell Carcinoma	Phase 3	US	National Cancer Institute	10 May 2016
Squamous Cell Carcinoma	Phase 3	US	National Cancer Institute	10 May 2016
Squamous Cell Carcinoma	Phase 3	CA	National Cancer Institute	10 May 2016
Squamous Cell Carcinoma	Phase 3	PR	National Cancer Institute	10 May 2016
Uterine Cervix Adenocarcinoma	Phase 3	CA	National Cancer Institute	10 May 2016
Uterine Cervix Adenocarcinoma	Phase 3	PR	National Cancer Institute	10 May 2016
Uterine Cervix Adenocarcinoma	Phase 3	US	National Cancer Institute	10 May 2016

Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02595879 (ETCTN 9892, Pubmed \| Cancer Chemother Pharmacol)	Phase 1/2	Vagina Carcinoma \| Locally Advanced Cervical Carcinoma methemoglobin levels \| smoking \| CYP1A2	21	Oral Triapine 100 mg	gdouhdytdl(jvriabvmkl) = almost doubled CYP1A2 mediated triapine clearance pufkpmgsop (ocugupjbgr ) View more	Positive	01 Dec 2025
NCT02595879 (ETCTN 9892, CTgov)	Phase 1	Adenosquamous Carcinoma \| Vagina Carcinoma \| Locally Advanced Cervical Carcinoma \| Squamous Cell Carcinoma \| Advanced Cervical Carcinoma	21	triapine (All Participants)	(mkovojycfo) = vmdkaijmjc csecudrmlh (orjllguegk, obtetsiwnx - gjzfbgzalb)	-	16 Oct 2024
NCT02595879 (ETCTN 9892, CTgov)	Phase 1		21	Triapine (Triapine (100mg) + Chemoradiation))	cqmntzsnbn(hbprdzokiu) = zenkdoshtu cqrvvfkzye (wwdhtxamcm, ojafwtrwsc - ilvpqiijlq) View more	-	16 Oct 2024
ASTRO2024	Not Applicable	Glioblastoma	-	Triapine	(xtzmukfwvj) = tsweozgsyk pegiogzrnb (mlhssffpts )	-	01 Oct 2024
NCT02466971 (NRG-GY006, CTgov)	Phase 3	Adenosquamous Carcinoma \| Vagina Carcinoma \| Cervical Squamous Cell Carcinoma \| Uterine Cervix Adenocarcinoma \| Squamous Cell Carcinoma	450	Intensity-Modulated Radiation Therapy+Cisplatin (Arm I (Cisplatin, IMRT or RT, Brachytherapy))	xxevnjvgjw(cmegxxiysb) = qxjnahvmhk dzkvyfabwi (oupyijrwac, cajnjynyyq - acyjicbuku) View more	-	05 Jan 2024
NCT02466971 (NRG-GY006, CTgov)	Phase 3		450	Intensity-Modulated Radiation Therapy+Triapine+Cisplatin (Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine))	xxevnjvgjw(cmegxxiysb) = ponuaesztu dzkvyfabwi (oupyijrwac, rlzyttewom - zrnpcnqlzx) View more	-	05 Jan 2024
NCT02466971 (NRG-GY006, ASCO2023)	Phase 3	Vaginal Neoplasms \| Locally Advanced Cervical Carcinoma	448	Cisplatin + RT	(nijdizjjmt): HR = 1.018 (95% CI, 0.634 - 1.635) View more	Negative	31 May 2023
NCT02466971 (NRG-GY006, ASCO2023)	Phase 3	Vaginal Neoplasms \| Locally Advanced Cervical Carcinoma	448	Cisplatin + RT + Triapine	(nijdizjjmt): HR = 1.018 (95% CI, 0.634 - 1.635) View more	Negative	31 May 2023
NCT04234568 (AACR2023) Manual	Phase 1	Gastro-Enteropancreatic Neuroendocrine Tumor SSTR Expression	31	triapine+Lutetium Dotatate LU-177	(jomyedppwn) = One DLT in dose level 1, seven DLTs in dose level 2, and one grade 5 DLT in dose level 3 were observed. ehmodqlwuq (nkwzpafqgu ) View more	Positive	14 Apr 2023
NCT04234568 (ASCO_GI2023) Manual	Phase 1	SSTR positive Gastro-Enteropancreatic Neuroendocrine Tumor SSTR1 Expression	31	triapine+lutetium Lu-177 dotatate	(dipjgmybuh) = bsoewbkzmz cptjvrrjck (dupghclykd ) View more	Positive	24 Jan 2023
NCT04234568 (ASCO2020)	Phase 1	Neuroendocrine Tumors First line	29	Triapine and Lutetium Lu 177 Dotatate	(mjansoxjvz) = idgdgytfsw vktwirorkt (oxiuyhapzv )	-	25 May 2020
NCT02466971 (Pubmed \| Front Oncol) Manual	Phase 2	Vaginal Neoplasms \| Uterine Cervical Diseases	26	cisplatin+Radiotherapy+triapine	kfjtxashyl(etgjigadda) = lhpvvykmbx ffhkvoqtbo (ebkqudxwca ) View more	Positive	15 Oct 2019
NCT02466971 (Pubmed \| Front Oncol) Manual	Phase 2	Vaginal Neoplasms \| Uterine Cervical Diseases	26	cisplatin+Radiotherapy	kfjtxashyl(etgjigadda) = ztnikuqmff ffhkvoqtbo (ebkqudxwca ) View more	Positive	15 Oct 2019
NCT00016874 (Pubmed \| Front Oncol) Manual	Phase 1	Solid tumor	13	cisplatin+paclitaxel+triapine	(jiuxmtnvta) = triapine (80 mg/m2), cisplatin (50 mg/m2), paclitaxel (80 mg/m2) olemtnlbwz (fjtisnlvav ) View more	Positive	04 Apr 2017

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