A Phase 1/2 Unblinded Trial of Carboxyamidotriazole Orotate (CTO) Alone or in Combination With Lomustine for Bevacizumab-Naïve Adult Patients With Recurrent Malignant Glioma

This is a Phase 1/2 study of the combination of CTO with lomustine in patients with recurrent malignant glioma to be treated at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke. The Primary Objectives are:
Phase 1: To determine the maximum tolerated dose (MTD) of CTO when combined with lomustine among patients with recurrent malignant glioma (World Health Organization (WHO) grade III or IV) who have not been previously treated with bevacizumab.
Phase 2: To assess the efficacy of CTO (either in monotherapy or in combination with lomustine) compared to lomustine alone in patients with recurrent WHO grade IV malignant gliomas that have not been previously treated with bevacizumab based upon 6-month progression free survival (PFS6).
Note: This study was terminated early due to funding issues. At the time of termination, the study was still in Phase 1 and no MTD for the combination of CTO and lomustine had been determined for this population. Phase 2 will not proceed.

开始日期2014-05-01

申办/合作机构

Duke University

[+1]

NCT01954030 / Terminated临床1期IIT

A Phase 1/2 Trial of Carboxyamidotriazole Orotate (CTO) Alone or in Combination With Bevacizumab for Adult Patients With Recurrent Malignant Glioma Post-Bevacizumab Failure

The primary objectives of the study are to determine the maximum tolerated dose (MTD) of Carboxyamidotriazole Orotate (CTO) when combined with standard dosing of bevacizumab among patients with recurrent malignant glioma (WHO grade III or IV) that have previously failed bevacizumab (Phase 1); to determine the activity of CTO alone in bevacizumab-failure WHO grade IV malignant glioma patients (Phase 2, Arm 1); to determine the activity of CTO plus bevacizumab in bevacizumab-failure WHO grade IV malignant glioma patients (Phase 2, Arm 2).
This study was terminated early due to funding issues. At the time of termination, the study was still in Phase 1 and no MTD for the combination of CTO and bevacizumab had been determined for this population. Phase 2 will not proceed.

开始日期2013-10-01

申办/合作机构

Duke University

[+1]

NCT01107522 / Active, not recruiting临床1期

A Phase I Study of Oral Carboxyamidotriazole Orotate (CTO) Titrated as a Single Agent in Patients With Advanced or Metastatic Solid Tumors and Titrated in Combination Therapy With Temodar® for Patients With Glioblastoma and Other Recurrent Malignant Gliomas or in Combination With Temodar® and Radiation Therapy for Patients With Newly Diagnosed Glioblastoma and Malignant Gliomas

The purpose of this study is to determine the safety, tolerability, and the maximum tolerated dose/recommended phase II dose of carboxyamidotriazole orotate (CTO) as a single agent in patients with advanced or metastatic solid tumors; in combination with oral Temodar® in patients with glioblastoma or other recurrent malignant gliomas; or in combination with oral Temodar® and radiation therapy in patients with newly diagnosed glioblastoma or other malignant gliomas.

开始日期2010-05-01

申办/合作机构

Tactical Therapeutics, Inc.

100 项与 Carboxyamidotriazole orotate 相关的临床结果

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100 项与 Carboxyamidotriazole orotate 相关的专利（医药）

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188

项与 Carboxyamidotriazole orotate 相关的文献（医药）

2023-07-01·Experimental parasitology

Polyalthic acid and oleoresin from Copaifera trapezifolia Hayne reduce Toxoplasma gondii growth in human villous explants, even triggering an anti-inflammatory profile

Article

作者: Martinez, Aryani Felixa ; Teixeira, Samuel Cota ; Barbosa, Bellisa Freitas ; Veneziani, Rodrigo Cassio ; Ambrosio, Sergio Ricardo ; de Souza, Guilherme ; Bastos, Jairo Kenupp ; Silva, Rafaela Jose ; Ferro, Eloisa Amalia ; Martins, Carlos Henrique ; Rosini, Alessandra Monteiro

Due to the lack of efficient antiparasitic therapy and vaccines, as well as emerging resistance strains, congenital toxoplasmosis is still a public health issue worldwide. The present study aimed to assess the effects of an oleoresin obtained from the species Copaifera trapezifolia Hayne (CTO), and an isolated molecule found in the CTO, ent-polyalthic acid (ent-15,16-epoxy-8(17),13(16),14-labdatrien-19-oic acid) (named as PA), against T. gondii infection. We used human villous explants as an experimental model of human maternal-fetal interface. Uninfected and infected villous explants were exposed to the treatments; the parasite intracellular proliferation and the cytokine levels were measured. Also, T. gondii tachyzoites were pre-treated and the parasite proliferation was determined. Our findings showed that CTO and PA reduced efficiently the parasite growth with an irreversible action, but without causing toxicity to the villi. Also, treatments reduced the levels of IL-6, IL-8, MIF and TNF by villi, what configures a valuable treatment option for the maintenance of a pregnancy in an infectious context. In addition to a possible direct effect on parasites, our data suggest an alternative mechanism by which CTO and PA alter the villous explants environment and then impair parasite growth, since the pre-treatment of villi resulted in lower parasitic infection. Here, we highlighted PA as an interesting tool for the design of new anti-T. gondii compounds.

2023-06-01·Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists

Variation in the use of compulsory community treatment orders between district health boards in New Zealand

Article

作者: Beaglehole, Ben ; Frampton, Chris ; Lees, Mathew ; Newton-Howes, Giles

Objective:

To report rates of Compulsory Community Treatment Order (CTO) use by District Health Boards (DHBs) in New Zealand and analyse whether socio-demographic factors explain any variability.

Methods:

The annualised rate of CTO use per 100,000 population was calculated for the years 2009–2018 using national databases. Rates were adjusted for age, gender, ethnicity, and deprivation and are reported according to DHBs to allow comparisons between regions.

Results:

The annualised rate of CTO use for New Zealand was 95.5 per 100,000 population. CTO use varied between DHBs from 53 to 184 per 100,000 population. Standardising for demographic variables and deprivation made little difference to this variation. CTO use was higher in males and young adults. Rates for Māori were more than three times that of Caucasian people. CTO use increased as deprivation became more severe.

Conclusions:

CTO use increases with Maori ethnicity, young adulthood, and deprivation. Adjusting for socio-demographic factors does not explain the wide variation in CTO use between DHBs in New Zealand. Other regional factors appear to be the major driver of variation in CTO use.

2023-04-14·BJPsych open

Benefits following community treatment orders have an inverse relationship with rates of use: meta-analysis and meta-regression.

Review

作者: Siskind, Dan ; McMahon, Laura ; Kisely, Steve

BACKGROUND:

Community treatment order (CTO) use in Australia and New Zealand ranges from less than 40 per 100 000 population in Western Australia and Canterbury to over 100 per 100 000 in Victoria, South Australia and Waitemata. Recent publications on CTO use now permit a meta-regression to investigate whether differences in CTO use by jurisdiction affect either the possible predictors or outcomes of CTOs.

AIMS:

To assess whether factors associated with CTO placement or subsequent outcomes vary by rates of use.

METHOD:

A systematic search of PubMed/Medline, Embase, CINAHL, the Cochrane Central Register of Controlled Trials and PsycINFO for any Australian or New Zealand study comparing CTO cases with controls receiving voluntary psychiatric treatment. This study was prospectively registered with PROSPERO (protocol registration number: CRD42022351500).

RESULTS:

There were 35 articles from 16 studies identified in the search, plus unpublished data from a further study. Of these, 29 publications were included in meta-analyses. Two were from New Zealand. People who were male, single and not engaged in work, study or home duties were significantly more likely to be on CTOs. In addition, those from migrant backgrounds were 47% more likely to be on an order. On meta-regression, cases in jurisdictions with higher CTO rates had higher proportions of females or individuals with diagnoses other than non-affective psychoses. High-use jurisdictions were also less likely to show reductions in readmission rates or bed-days.

CONCLUSIONS:

There are marked differences in the possible predictors and outcomes of CTO placement between high- and low-use jurisdictions in Australia and New Zealand. These findings may have implications elsewhere and indicate that better-targeted CTO placement might improve outcomes.

项与 Carboxyamidotriazole orotate 相关的新闻（医药）

2023-06-08

·Pharmaceutical Technology

UK’s MHRA expands approval for Merz Therapeutics’ XEOMIN

Merz Therapeutics’ XEOMIN is injected intramuscularly to improve muscle tone. Credit: Mufid Majnun on Unsplash. The UK’s medicines and healthcare products regulatory agency (MHRA) has granted approval for a new indication for Merz Therapeutics’ XEOMIN (incobotulinumtoxinA) to treat focal spasticity of the lower limbs affecting the ankle joint. The therapy was previously approved in the UK to treat upper limb spasticity. Recommended Reports Reports LOA and PTSR Model - Carboxyamidotriazole Orotate in Glioblastoma Multiforme (GBM) GlobalData Reports LOA and PTSR Model - Valbenazine Tosylate in Chorea GlobalData View all The expanded approval allows the company to provide holistic support to those living with spasticity who need comprehensive treatment. The active ingredient in XEOMIN is incobotulinumtoxinA. It is injected intramuscularly to improve muscle tone. The therapy blocks nerve impulses to the muscles to weaken voluntary muscle contraction. It relieves abnormal muscle tone by inhibiting the release of acetylcholine from the peripheral nerve endings. Merz Therapeutics stated that XEOMIN can now be used to treat lower and upper limbs individually or simultaneously, by adjusting the dose as required. Merz Therapeutics CEO Stefan König stated: “The label extension in the UK is an important step for Merz Therapeutics and the patients that we serve. “With the UK becoming the second market, following Japan, to grant approval for the treatment of lower limb spasticity affecting the ankle joint, it establishes the UK as the pioneering European country in this area.” The company noted that 400 units per injection is the maximum dose of XEOMIN required to treat lower limbs. 500 units is the maximum dose for the combined treatment of upper and lower limb spasticity. XEOMIN has already received approval in more than 75 countries across the world for the treatment of blepharospasm, cervical dystonia, upper and lower limb spasticity and sialorrhea.

上市批准

2022-12-13

·PRNewswire

Tactical Therapeutics, Inc., Developer of CTO Treatments for Glioblastoma, Selected to Present at MedInvest Oncology Investor Conference December 14-15 in New York

Founder and CEO Rashida Karmali Ph.D., J.D., is a respected pioneer in cancer research, specializing in drug discovery and development Carboxyamidotriazole Orotate (CTO) shows promising results in pre-clinical and Phase I trials A privately funded clinical stage company, TTI is raising money for Phase II clinical trials NEW YORK, Dec. 13, 2022 /PRNewswire/ -- Tactical Therapeutics, Inc. (TTI), a clinical stage biopharma, has been selected to present at the MedInvest Oncology Investor Conference taking place December 14-15, 2022, in New York, N.Y. "We are honored to be selected to present at this unique event," said Rashida Karmali, Ph.D., CEO of Tactical Therapeutics . "We welcome the chance to interact with many of the world's most accomplished leaders and investors who are all dedicated to improving the health and lives of patients with glioblastoma (GBM) and difficult to treat solid cancers." About Glioblastoma, recurrent (rGBM) and newly diagnosed (nGBM) Glioblastoma, the brain tumor that killed Senator Ted Kennedy, Beau Biden and Senator John McCain, is still mostly untreatable. Recent reports suggest veterans of Vietnam, Iraq and Afghanistan wars who were exposed to burn pits later developed GBM. GBM exhibits debilitating neurological symptoms and suicide rates for GBM patients are higher compared to those with other cancers. Since 2005, GBM, an orphan disease (approximately 18,000/yr), has a median overall survival (OS) of between 12 to 20 months in newly diagnosed GBM with surgery, radiotherapy (with temozolomide) and adjuvant temozolomide, plus tumor treating fields. rGBM recurs frequently within a year with a median OS of 10 months. TTI's oral, safe and brain-penetrating drug, Carboxyamidotriazole Orotate (CTO), showed efficacy with significantly improved OS from 10 months to 28 months+ in nGBM in Phase IB trial, with published results (J. Clin Oncology, (2018)36:1702-1709). Dr. Antonio Omuro, who oversaw the CTO Phase I clinical trial, had this to say about the promising treatment: "In 27 Recurrent GBM patients, 1 complete and 6 partial responses were observed in patients who had been in several previous trials, including patients previously exposed to bevacizumab, who are the most challenging patients to treat. Radiographic responses are rarely seen in glioblastoma trials, therefore these are really promising results. Excellent survival was observed in 15 newly diagnosed GBM (13/15), with median overall survival not reached after 28 months; 2-year survival 62%; 1-year survival 93%. Two patients remain recurrence free at 5 years. "The safety profile was excellent, and we were also able to demonstrate that CTO crosses the blood brain barrier and can achieve high concentrations in brain tumors. Overall, the Phase IB trials of CTO in GBM patients showed highly promising efficacy and safety in patients with very advanced disease." About Carboxyamidotriazole Orotate (CTO) & Intellectual Property (IP) CTO is a patented first-in-class inhibitor of genes of non-voltage dependent calcium signaling associated with multiple oncolytic pathways and calcium channels. At clinically relevant CTO levels, differential expression of some mRNA showed inhibition of transcriptional signatures of several oncogenes, and in contrast activation of tumor suppressors. The IP portfolio includes 8 U.S. and 75 International patents lasting to 2033. About Tactical Therapeutics, Inc Tactical Therapeutics, Inc., is a privately funded company that has developed a patented lead therapeutic, CTO, for glioblastoma and other solid cancers. Three Phase I trials have been completed. Two Phase II trials are planned for rGBM and nGBM. The company is pursuing partnering and licensing strategies. Contact for Tactical Therapeutics, Inc: Rashida Karmali, 212-651-9653; 917-763-7196; [email protected] SOURCE Tactical Therapeutics, Inc.

临床1期临床结果临床2期ASCO会议

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适应症	最高研发状态	国家/地区	公司	日期
胶质瘤	临床2期	美国	Tactical Therapeutics, Inc.	2018-06-18
复发性胶质瘤	临床1期	美国	Tactical Therapeutics, Inc.	2013-10-01
复发性恶性胶质瘤	临床1期	美国	Tactical Therapeutics, Inc.	2013-10-01
胶质母细胞瘤	临床1期	美国	Tactical Therapeutics, Inc.	2010-05-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01107522 (Pubmed \| J Urol)	临床1期	胶质瘤 \| 复发性胶质母细胞瘤	-	Carboxyamidotriazole orotate	鹹憲範繭願鑰淵淵構蓋(壓壓築鏇壓願醖壓衊鹽) = 衊鏇鏇鑰構繭遞積鏇積襯選鏇選夢獵鹽鏇範範 (構範齋窪蓋夢膚選簾網 ) 更多	-	2018-06-10
NCT01107522 (ASCO2016)	临床1期	多形性胶质母细胞瘤	15	Carboxyamidotriazole orotate (CTO)	鬱淵鑰鏇窪顧壓繭蓋鏇(顧蓋鬱簾遞鹹構膚憲醖) = decreased platelets and neutrophils 淵觸範艱製衊壓獵選簾 (餘願淵簾鬱廠範獵鑰遞 ) 更多	积极	2016-05-20
NCT01989052 (ASCO2015)	临床1期	复发性恶性胶质瘤	9	Carboxyamidotriazole orotate (CTO)	顧遞窪繭憲範顧繭鑰廠(糧窪鹹鑰選觸遞觸夢網) = 築餘艱繭艱繭淵鏇網觸糧艱網製觸餘簾蓋積膚 (顧網鏇網顧襯艱窪壓鑰 )	-	2015-05-20
NCT01954030 (ASCO2015)	临床1期	复发性恶性胶质瘤	15	Carboxyamidotriazole orotate (CTO)	觸築觸鑰鏇夢鹽醖積鬱(繭餘顧壓製觸簾網壓襯) = 繭壓選積夢築衊鹽鏇醖齋構夢膚膚淵選鹽醖鏇 (顧窪糧構壓選艱鏇襯膚 ) 更多	-	2015-05-20
NCT01107522 (ASCO2014)	临床1期	复发性恶性胶质瘤	15	Carboxyamidotriazole orotate (CTO)	鏇鏇醖構製醖選選壓艱(選鬱鑰製艱蓋網襯網鏇) = 繭鑰憲窪窪遞窪衊鬱蓋願壓蓋鏇製製襯膚繭艱 (餘顧壓醖壓糧觸築鏇製 )	-	2014-05-20
NCT01107522 (ASCO2014)	临床1期	复发性恶性胶质瘤	15	Temozolomide (TMZ)	鏇鏇醖構製醖選選壓艱(選鬱鑰製艱蓋網襯網鏇) = 齋餘鹽積鬱壓鑰鹽簾簾願壓蓋鏇製製襯膚繭艱 (餘顧壓醖壓糧觸築鏇製 )	-	2014-05-20