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

Duke University

[+1]

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]

100 Clinical Results associated with Carboxyamidotriazole orotate

100 Translational Medicine associated with Carboxyamidotriazole orotate

100 Patents (Medical) associated with Carboxyamidotriazole orotate

150

Literatures (Medical) associated with Carboxyamidotriazole orotate

01 Jul 2026·JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Randomized, Placebo-Controlled Trial of Chronic Total Occlusion Percutaneous Coronary Intervention in Stable Angina

Article

Author: Khan, Sarosh ; O'Kane, Peter ; Demir, Ozan M ; Ibrahim, Abdalla ; Mohdnazri, Shah R ; Sajjad, Uzma ; Brilakis, Emmanouil S ; Keeble, Thomas R ; Cook, Christopher M ; Kelly, Paul ; Tang, Kare ; Karamasis, Grigoris V ; Robertson, Craig ; Butt, Haroun ; Davies, John R ; Spratt, James C ; Simpson, Rupert ; Fawaz, Samer ; Al-Lamee, Rasha ; Shun-Shin, Matthew

BACKGROUND:

Percutaneous coronary intervention for coronary chronic total occlusion (CTO PCI) is offered for symptom and quality of life improvement, despite the absence of blinded randomized evidence.

OBJECTIVES:

The aim of this study was to assess the efficacy of CTO PCI in the first randomized, placebo-controlled trial of CTO PCI.

METHODS:

ORBITA-CTO is a multicenter, randomized, blinded trial comparing CTO PCI with a placebo procedure. Patients had angina attributable to a single-vessel CTO, without bystander coronary disease. Angina symptoms were recorded daily using the ORBITA app. After dual-injection coronary angiography, patients were randomized to either CTO PCI or placebo. Blinding was maintained using auditory isolation and deep conscious sedation. Antianginal medications were stopped at randomization and reintroduced on a patient-initiated protocol. At the 6-month follow-up, assessments were repeated. The primary efficacy outcome was the angina symptom score, an ordinal scale combining the daily symptom burden assessed by the ORBITA app, antianginal use, and over-ride events. Secondary outcomes were symptom and quality of life questionnaires and blinding fidelity.

RESULTS:

Between October 19, 2021 and October 21, 2025, 50 patients were randomly assigned to CTO PCI (n = 25) or placebo (n = 25). One patient randomized to PCI was withdrawn during the procedure because of a complication. All 50 patients were included in the primary analysis. Compared with placebo, CTO PCI resulted in an immediate and sustained improvement in the angina symptom score (OR: 4.38; 95% credible interval [CrI]: 1.57-12.69; probability of benefit [Pr{Benefit}] = 0.996), arising from a clear reduction in the number of episodes of angina (OR: 4.38; 95% CrI: 1.55-11.78; Pr[Benefit] = 0.997). This resulted in an additional 30.6 days free of angina (95% CrI: 11.1-50.7; Pr[Benefit] >0.999). Improvements were also observed with the Seattle Angina Questionnaire in angina frequency (+10.7; 95% CrI: 1.4-20.2; Pr[Benefit] = 0.988), physical limitation, quality of life, and summary score and Canadian Cardiovascular Society class. Blinding of patients, staff, and researchers was maintained.

CONCLUSIONS:

In patients with symptomatic single-vessel CTO, CTO PCI improves angina beyond placebo. (A Placebo-controlled Trial of Chronic Total Occlusion Percutaneous Coronary Intervention for the Relief of Stable Angina [ORBITA-CTO]; NCT05142215).

01 Jul 2026·BJPsych Open

Availability and restrictiveness of community treatment orders across 33 European countries

Article

Author: Chihai, Jana ; Aluh, Deborah Oyine ; Rugkåsa, Jorun ; Birkeland, Søren Fryd ; Chatzittofis, Andreas

Background:

Community treatment orders (CTOs) permit compulsory mental healthcare outside hospital. Such orders have become part of an increasing number of mental health laws, even if there is a lack of consensus on their effects, negative personal experiences, diverging ethical positions and expectations that governments should reduce or abandon coercive practices. It is therefore surprising that there is limited research describing the availability and restrictiveness of CTO legislation, and we found no comprehensive European study. Such studies could contribute to clarification of differing positions and, through that, informing further research and discussions of how to promote voluntary options in clinical practice.

Aims:

To establish the availability of CTO legislation across Europe, and how regimes in different ways restrict the person.

Method:

Data were collected from 33 European countries through a network of researchers and practitioners, and links to relevant legislation were provided.

Results:

We found 13 CTO regimes across the 33 countries: two-thirds therefore managed without them. Despite some variation, most law texts specified restrictions related to legal criteria, enforcement mechanisms and safeguards. Restrictions on the person were often specified in separate tailored plans, and most regimes permitted indefinite renewals, which means that the duration of restrictions can be ascertained only in retrospect.

Conclusions:

CTO law texts preclude scrutiny of overall restrictiveness, which might add to current uncertainties regarding the proportionality of CTOs and their role in balancing individuals’ rights to both autonomy and care. The current policy drive towards community care should not automatically lead to new CTO regimes until their effectiveness and de facto restrictiveness are established.

01 May 2026·Cardiology in review

The Presence of Chronic Total Occlusion in Noninfarct-Related Arteries Is Associated With Higher Mortality and Worse Patient Outcomes Following Percutaneous Coronary Intervention for STEMI: A Systematic Review, Meta-Analysis and Meta-Regression

Review

Author: Viraj Shah ; Surabhi Maheshwari ; Samia Aziz Sulaiman ; Haania Shahbaz ; Aman Goyal ; Sourbha S. Dani ; Amir Humza Sohail ; Urooj Shamim ; Abu Baker Sheikh ; Pauras Mhatre ; Abhigan Babu Shrestha

Reperfusion therapy with percutaneous coronary intervention improves outcomes in patients with ST-elevation myocardial infarction. We conducted a meta-analysis to assess the impact of chronic total occlusion (CTO) in noninfarct-related artery on the outcomes of these patients. Comprehensive searches were performed using PubMed, Google Scholar, and EMBASE. The primary endpoint was the 30-day mortality rate, with secondary endpoints including all-cause mortality, repeat myocardial infarction, and stroke. Forest plots were created for the pooled analysis of the results, with statistical significance set at P < 0.05. A total of 19 studies were included in this meta-analysis, with 23,989 patients (3589 in CTO group and 20,400 in no-CTO group). The presence of CTO was associated with significantly higher odds of 30-day mortality [18.38% vs 5.74%; relative risk (RR), 3.69; 95% confidence intervals (CI), 2.68–5.07; P < 0.00001], all-cause mortality (31.00% vs 13.40%; RR, 2.79; 95% CI, 2.31–3.37; P < 0.00001), cardiovascular-related deaths (12.61% vs 4.1%; RR, 2.61; 95% CI, 1.99–3.44; P < 0.00001), and major adverse cardiovascular events (13.64% vs 9.88%; RR, 2.08; 95% CI, 1.52–2.86; P < 0.00001) than the non-CTO group. No significant differences in repeated myocardial infarction or stroke were observed between the CTO and non-CTO groups. Our findings underscore the need for further research on the benefits and risks of performing staged or simultaneous percutaneous coronary intervention for CTO in the noninfarct-related artery in patients with ST-elevation myocardial infarction.

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.

to view more data

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
Sjogren's Syndrome	Preclinical	China	Peking Union Medical College	28 Apr 2025

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	ofvbsussvf(fxlmwjkuls) = tjiuiytthy ndjufojhwr (wjrlnuvegf, (8.0 - 14.8))	Positive	27 Apr 2025
phase IB trial (AACR2025)	Phase 1	Glioblastoma \| Glioma	41	Lomustine	ofvbsussvf(fxlmwjkuls) = brruxmdnag ndjufojhwr (wjrlnuvegf, (6.1 - 7.7))	Positive	27 Apr 2025
NCT01107522 (Pubmed \| J Clin Oncol)	Phase 1	Glioblastoma \| Glioma	-	Carboxyamidotriazole orotate	vhxlwcvizm(xzguxjmeql) = zlfstyyxfv bacjwpjuwj (viqdtenqhf ) View more	-	10 Jun 2018
NCT01107522 (ASCO2016)	Phase 1	Glioblastoma Multiforme	15	Carboxyamidotriazole orotate (CTO)	aamfvpqlfu(bshxjwedif) = decreased platelets and neutrophils qbvzfrtklz (jmqttvgjxc ) View more	Positive	20 May 2016
NCT01954030 (ASCO2015)	Phase 1	Recurrent Malignant Glioma	15	Carboxyamidotriazole orotate (CTO)	ojzlclvecq(caofuuhmtb) = ijgpzpjfqo bhxmtewsdn (ezxeudwekr ) View more	-	20 May 2015
NCT01989052 (ASCO2015)	Phase 1	Recurrent Malignant Glioma	9	Carboxyamidotriazole orotate (CTO)	okndgnbyfq(kyurkiwwhd) = dkwcyrpwvr nhwkplmdow (uiptuslwwm )	-	20 May 2015

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