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.

Start Date01 May 2014

Sponsor / Collaborator

Tactical Therapeutics, Inc.

NCT01954030

/ TerminatedPhase 1IIT

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.

Start Date01 Oct 2013

Sponsor / Collaborator

Duke University

[+1]

ACTRN12612001130853

/ Not yet recruitingPhase 2IIT

A Phase IIa Dose-Ranging Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetic Profile of Multiple Escalating Doses of Carboxyamidotriazole Orotate (CTO) in Patients with Neovascular Age Related Macular Degeneration (AMD)

Start Date01 Dec 2012

Sponsor / Collaborator-

100 Clinical Results associated with Carboxyamidotriazole orotate

100 Translational Medicine associated with Carboxyamidotriazole orotate

100 Patents (Medical) associated with Carboxyamidotriazole orotate

212

Literatures (Medical) associated with Carboxyamidotriazole orotate

01 Jun 2025·International Journal of Mental Health Nursing

Community Treatment Orders in Australia in the Context of International Literature: A Narrative Review of Consumers, Families and Health Professionals' Perspectives

Review

Author: Harvery, Madeleine ; Wright, Shelley ; Morgan, Matthew ; Harrington, Rosamund ; Yule, Elisa

ABSTRACT:

A community treatment order (CTO) sets out legal conditions requiring a person experiencing mental illness to receive treatment and medication while living in the community. Although CTOs are used internationally in most high‐income nations, CTO use in Australia is very high compared with world standards. CTOs are a contentious issue in mental health practice. While they aim to protect both consumers and society, they often interfere with personal freedom and trust between consumers and mental health professionals. International and Australian research is inconclusive about the effectiveness of CTOs in achieving their clinical aims. Australian research overwhelmingly reports consumers' experience with CTOs as coercive and distressing. Families generally support CTOs but are unhappy with certain aspects of the process. Consumers and families' feelings about CTOs often depend on how much they trust the mental health team, the support they receive, and the relationship between the consumer and mental health professional. Health professionals experience significant challenges balancing therapeutic care with their role carrying out CTOs. Local treatment culture, problems in the mental health system and staff attitudes also influence how CTOs are used. There is a lack of recent and high‐quality guidance to inform CTO decision‐making for mental health professionals. This perspective paper is presented as a narrative literature review, which proposes that if CTOs are used in clinical practice, close consideration towards how and why they are implemented is warranted.

01 Mar 2025·LIFE SCIENCES

Carboxyaminotriazole: A bone savior in collagen-induced arthritis—Halting osteoclastogenesis via interleukin-1β downregulation

Article

Author: Zhu, Lei ; Yang, Mei ; Lu, Shan ; Li, Juan

AIMS:

Rheumatoid arthritis (RA), a prevalent autoimmune disease, features inflammation and bone erosion, correlating with osteoclast hyperactivation and enhanced responsiveness to inflammatory factors. Reducing osteoclast formation and inflammatory mediator expression might avert bone erosion in RA. Carboxyaminotriazole (CAI) holds potential for treating autoinflammatory disorders and impeding cancer-related bone metastases. Yet, its bone-protective role and mechanism remain elusive. This study targets to explore the impacts and underlying mechanisms of CAI in preventing bone erosion in RA.

MATERIALS AND METHODS:

A collagen-induced arthritis (CIA) rat model was utilized to evaluate the anti-RA potential of CAI. CCK-8, TRAP staining, TRAP activity assay, pit formation assay, RT-qPCR, Western blotting, immunofluorescence, and ELISA, were conducted to assess the effects and potential mechanisms of CAI in the management of RA.

KEY FINDINGS:

CAI not only reduces inflammatory symptoms, but it also offers superior bone protection compared to methotrexate (MTX) and works synergistically with MTX, the preferred anchoring agent for the treatment of RA. In vitro studies show that CAI inhibits osteoclast differentiation and function, as well as the expression of specific genes, by inhibiting NF-κB/MAPK pathways and reducing IL-1β levels. The deletion of Il-1 and the application of IL-1β inhibitors suggest that CAI retards osteoclastogenesis through the downregulation of IL-1β.

SIGNIFICANCE:

CAI may have therapeutic value in treating RA-related bone erosion, likely due to its inhibition of overactive osteoclasts by suppressing the NF-κB/MAPK pathways and the subsequent expression of IL-1β.

01 Mar 2025·Annales Pharmaceutiques Francaises

Article

Author: Delporte, Lucas ; Masse, Morgane ; Delhaye, Cédric ; Décaudin, Bertrand ; Rihani, Emir Kaïs ; Lauerière, Claire ; Brianceau, Marie-Caroline ; Odou, Pascal

OBJECTIVES:

Chronic total occlusion (CTO) of coronary arteries is defined as complete absence of antegrade coronary flow without iodine passage, since more than 3 months. Coronary revascularization is a highly resource-intensive angioplasty procedure involving numerous medical devices (MDs). Its consumption and associated costs are not covered by either the medical act classification (CCAM) or the hospitalization fees and additional MD funding. The primary aim of this study is to analyze the financial sustainability of this activity for a public healthcare institution and to assess the budgetary impact of CTO treatment on the most expensive items of expenditure. The secondary aim is to describe the patient's intra-hospital pathway.

METHODS:

CTO revascularization stays are categorized under the code 05K06 "Vascular Stents without Myocardial Infarction". Major cost items were identified using national coded expenditure data and compared with those from our cost study. Every CTO intervention from January to November 2021 were retrospectively retrieved. Establishment purchase prices in 2021 were used to determine MD costs. Clinical data were extracted from electronic patient records. Operative data (procedure duration, professionals involved, and MD used) were extracted. Human Resources (HR) costs were integrated into the calculations. A Sankey diagram was created. Data are expressed as mean±standard deviation.

RESULTS:

In our study, 41 patients underwent 45 interventions. The median was 65 years. Seventy-eight percent of interventions were successful with a median duration of 113minutes. Two hundred and two different MD references were used, with 27% reimbursed additionally and 73% funded within the homogeneous group of stays (HGS). The total cost of MD described in the coded expenditure data is 2142€, of which 721€ is funded within the HGS. In our cohort, it represented averages of 2736€±1393€ and 1710€±926€, respectively. Regarding HR, the total cost described in the coded expenditure data was 442€ compared to 410€±169€ in our cohort. Finally, patient pathway analysis showed an average length of stay (LOS) of 1.8 days. Two pathways were identified depending on admission context: weekday hospitalization or cardiac intensive care.

CONCLUSIONS:

CTO revascularization is a planned intervention with a short LOS and a highly standardized patient pathway. Our study highlights a proliferation of MD references used during CTO revascularization due to innovative industrial developments. The cost differential with coded expenditure data confirms the need for a revision of the procedure and its categorization within an HGS, which is currently non-specific.

News (Medical) associated with Carboxyamidotriazole orotate

08 Jun 2023

·www.pharmaceutical-technology.com

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.

Drug Approval

13 Dec 2022

·www.prnewswire.com

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.

Phase 1Clinical ResultPhase 2ASCO

100 Deals associated with Carboxyamidotriazole orotate

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glioma	Phase 2	United States	Tactical Therapeutics, Inc.	18 Jun 2018
Recurrent Glioma	Phase 1	United States	Tactical Therapeutics, Inc.	01 Oct 2013
Advanced Malignant Solid Neoplasm	Phase 1	United States	Tactical Therapeutics, Inc.	01 May 2010
Recurrent Glioblastoma	Phase 1	United States	Tactical Therapeutics, Inc.	01 May 2010
Recurrent Malignant Glioma	Phase 1	United States	Tactical Therapeutics, Inc.	01 May 2010

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


phase IB trial (AACR2025)	Phase 1	Glioblastoma \| Glioma	41	CTO+TMZ	qezieenrug(zuarzamvbx) = dnkcgpykow mzfwgftwut (qvdbjykcff, (8.0 - 14.8))	Positive	27 Apr 2025
phase IB trial (AACR2025)	Phase 1	Glioblastoma \| Glioma	41	Lomustine	qezieenrug(zuarzamvbx) = oiziwayxaz mzfwgftwut (qvdbjykcff, (6.1 - 7.7))	Positive	27 Apr 2025
NCT01107522 (Pubmed \| J Clin Oncol)	Phase 1	Glioblastoma \| Glioma	-	Carboxyamidotriazole orotate	iaqskvwcea(qilureaacj) = fysxeoixwd hbzfztytxq (shwlpistgf ) View more	-	10 Jun 2018
NCT01107522 (ASCO2016)	Phase 1	Glioblastoma Multiforme	15	Carboxyamidotriazole orotate (CTO)	dghsxopvlr(ijxiysplpu) = decreased platelets and neutrophils nzyhxkpkxa (lriicewavo ) View more	Positive	20 May 2016
NCT01989052 (ASCO2015)	Phase 1	Recurrent Malignant Glioma	9	Carboxyamidotriazole orotate (CTO)	pmzessszwg(nbldhyozyy) = fsaircilvl prwfhixxwe (ztkfjmmcej )	-	20 May 2015
NCT01954030 (ASCO2015)	Phase 1	Recurrent Malignant Glioma	15	Carboxyamidotriazole orotate (CTO)	xkhqqqgito(nfttiikldb) = tpyqmslnrl xuctxxqodq (skkfbgexql ) View more	-	20 May 2015

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