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Solid Tumors, Glioblastoma, Recurrent Malignant GliomasPhase 1NCT01107522

Safety and Tolerability of Carboxyamidotriazole Orotate (CTO) in Solid Tumors or With Temodar® in Glioblastoma or Other Recurrent Malignant Gliomas or in Combination With Temodar® and Radiation Therapy for Patients With Newly Diagnosed Glioblastoma and Malignant Gliomas

A Phase 1 study testing CTO, CTO and Temodar® and CTO, Temodar®, Radiation therapy in people with Solid Tumors, Glioblastoma, Recurrent Malignant Gliomas, run by Tactical Therapeutics, Inc. at 4 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CTO, CTO and Temodar® and CTO, Temodar®, Radiation therapy
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
4 sitesUnited States
Study dates
May 2010to Jan 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically-confirmed solid tumors that are advanced or metastatic, and refractory after standard therapy, or for which there is no standard therapy.
  • Patients must have measurable disease as defined by RECIST version 1.1.
  • Patients must have received prior anticancer therapy or not be eligible for any established conventional therapy whether surgical or pharmacologic.
  • Patients must have recovered from all acute adverse effects (excluding alopecia) of prior therapies to baseline or <=grade 1 prior to study entry.
  • Patients must have a performance status of 0, 1, or 2.
  • Patients must be men and women >=18 years of age.
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  • Patients must have adequate bone marrow function, defined as an absolute neutrophil count >=1.5 x 10^9/L and a platelet count >= 100 x 10^9/L.
  • Patients must have adequate renal function, defined as serum creatinine <= 1.2 mg/dL (if > 1.2 mg/dL, a calculated creatinine clearance [by the Cockcroft-Gault method] must be >=60 mL/min/1.73 m^2).
  • Patients must have adequate hepatic function, defined as plasma total bilirubin <=1.5 mg, alanine transaminase (ALT) and aspartate transaminase (AST) <=2.5 X ULN. Patients with Gilbert's disease outside these limits are judged to be ineligible.
  • Female patients of childbearing potential must have a negative serum or urine pregnancy test result at time of pre-treatment screening.
  • Patients with reproductive potential must agree to use at least one form of barrier contraception prior to study entry and for up to 30 days beyond the last administration of study drug.
  • Patients must be judged to be capable by the Investigator of providing informed consent and must be willing to provide written informed consent prior to the start of any study specific procedures.
  • Patients should have a life expectancy of at least 12 weeks.
  • In addition to the inclusion criteria for adequate organ function as defined for the patients with advanced or metastatic solid tumors, patients enrolled in Arm C (Combination Therapy CTO and Temodar® in combination with radiation therapy) must meet the following inclusion criteria:
  • Patients must have histologically proven newly diagnosed glioblastoma or other malignant gliomas. Note: Patients with anaplastic oligodendroglioma with 1p/19q deletion or unknown 1p/19q status are not eligible
  • Patients must have a life expectancy of at least 8 weeks
  • Patients must have a Performance Status of 0, 1, or 2 (ECOG scale).
  • Patients must be men and women >=18 years of age.
  • Patients must have undergone an MRI scan performed within 14 days prior to registration and must be on a steroid dose that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required.
  • Patients under treatment with anti-epileptic drugs which are not known CYP3A4 inhibitors or inducers must have been receiving a stable dose for at least 2 weeks with no evidence of seizures at the time of registration.

Who cannot join

  • Patients may not have had prior chemotherapy, hormonal therapy, radiation therapy, or biologic therapy in the 4 weeks prior to study entry with the exception of mitomycin C or nitrosoureas, for which patients must be 6 weeks from prior treatment. For patients who have been treated with targeted therapy, 5 half-lives of that therapy (or 28 days, whichever is shorter) must have passed prior to enrollment in the study.
  • Patients may not have any concomitant condition that could compromise the objectives of this study and the patients' compliance and ability to tolerate this therapy and complete at least 2 cycles of therapy, including, but not limited to the following:
  • Congestive heart failure or uncontrolled angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension, or dysrhythmias.
  • Active infection.
  • Unstable diabetes mellitus
  • Psychiatric disorder that may interfere with consent and/or protocol compliance.
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  • Pregnant or breastfeeding women.
  • Patients with another malignancy in the past 3 years except: curatively treated non-melanoma skin cancer; or carcinoma in situ, of either cervix or breast, that does not require further treatment.
  • Patients with known HIV, HBV, or HCV infection.
  • Patients with an underlying diagnosis or disease state associated with an increased risk of bleeding.
  • Patients with central nervous system metastases. Baseline CT or MRI scan of brain is required only in the case of clinical suspicion of central nervous system metastases. Patients with evidence of brain involvement, leptomeningeal disease, or seizure disorder are also excluded.
  • Patients may not be treated with known CYP3A4 inhibitors or inducers.
  • Inclusion and Exclusion Criteria for Combination CTO Plus Temodar® (Treatment Arm B): Inclusion Criteria (Treatment Arm B)
  • In addition to the inclusion criteria for adequate organ function as defined for the patients with advanced or metastatic solid tumors, patients enrolled in Arm B (Combination Therapy CTO Plus Temodar-R) must meet the following inclusion criteria:
  • Patients must have histologically proven malignant glioblastoma or other recurrent malignant gliomas.
  • Measurable tumor must be present on gadolinium-enhanced MRI.
  • Patients must have a life expectancy of at least 8 weeks.
  • Patients must have a Performance Status of 0, 1, or 2 (ECOG scale).
  • Patients must be men and women >=18 years of age.
  • Patients must have recovered from all acute adverse effects (excluding alopecia) of prior therapies to baseline or <=grade 1 prior to study entry.
  • Patients must have shown unequivocal radiographic evidence for tumor progression by MRI scan to be performed within 14 days prior to registration and must be on a steroid dose that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI scan is required.
  • Patients who have undergone recent resection for recurrent or progressive malignant tumor will be eligible as long as all of the following conditions apply:
  • They have recovered from the effects of surgery
  • The extent of residual disease is assessed post-operatively, with an MRI scan done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, within 14 days prior to registration. If the 96-hour scan is more than 14 days before registration, the scan needs to be repeated.
  • Patients must have had prior radiation therapy with or without chemotherapy and must have progressed following radiation therapy and must have an interval of >=12 weeks from the completion of radiation therapy to registration date to minimize the possibility of pseudo-progression.
  • Patients under treatment with anti-epileptic drugs which are not known CYP3A4 inhibitors or inducers must have been receiving a stable dose for at least 2 weeks with no evidence of seizures at the time of registration.
  • Patients may not have had prior chemotherapy, hormonal therapy, or biologic therapy in the 4 weeks prior to study entry with the exception of mitomycin C or nitrosoureas, for which patients must be 6 weeks from prior treatment. For patients who have been treated with targeted therapy, 5 half-lives of that therapy (or 28 days, whichever is shorter) must have passed prior to enrollment in the study. Additional exceptions: The following specific drugs are permitted shorter recovery times: 14 days for vincristine, 21 days for procarbazine, and 7 days for non-cytotoxic agents such as interferon, tamoxifen, thalidomide, and cis-retinoic acid.
  • Patients may not have any concomitant condition that could compromise the objectives of this study and the patients' compliance and ability to tolerate this therapy and complete at least 2 cycles of therapy, including, but not limited to the following:
  • Congestive heart failure or uncontrolled angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension, or dysrhythmias.
  • Active infection.
  • Unstable diabetes mellitus.
  • Psychiatric disorder that may interfere with consent and/or protocol compliance.
  • Pregnant or breastfeeding women.
  • Patients with another malignancy in the past 3 years except: curatively treated non-melanoma skin cancer; or carcinoma in situ, of either cervix or breast, that does not require further treatment.
  • Patients with known HIV, HBV, or HCV infection.
  • Patients with an underlying diagnosis or disease state associated with an increased risk of bleeding.
  • Uncontrolled seizure activity.
  • Patients may not be treated with known CYP3A4 inhibitors or inducers.
  • Inclusion and Exclusion Criteria for Combination CTO and Temodar® in combination with radiation therapy (Treatment Arm C):
  • Patients may not have had any prior chemotherapy, hormonal therapy, or biologic therapy for gliomas.
  • Patients may not have any concomitant condition that could compromise the objectives of this study and the patients' compliance and ability to tolerate this therapy and complete at least 2 cycles of therapy, including, but not limited to the following:
  • Congestive heart failure or uncontrolled angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension, or dysrhythmias.
  • Active infection.
  • Unstable diabetes mellitus.
  • Psychiatric disorder that may interfere with consent and/or protocol compliance.
  • Pregnant or breastfeeding women.
  • Patients with another malignancy in the past 3 years except: curatively treated non-melanoma skin cancer; or carcinoma in situ, of either cervix or breast, that does not require further treatment.
  • Patients with known HIV, HBV, or HCV infection.
  • Patients with an underlying diagnosis or disease state associated with an increased risk of bleeding.
  • Uncontrolled seizure activity.
  • Patients may not be treated with known CYP3A4 inhibitors or inducers.
  • Patients with anaplastic oligodendroglioma with 1p/19q deletion or unknown 1p/19q status are excluded.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • New York University

    New York, New York, 10016

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10017

  • Providence Cancer Center

    Portland, Oregon, 97213

  • Oregon Health and Sciences University

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: 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.

Being tested
CTO, CTO and Temodar®, CTO, Temodar®, Radiation therapy
Medical subject headings
Glioblastoma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CTODrug

    Oral administration daily for 28 day cycles; starting dose of CTO = 50 mg/m2

  • CTO and Temodar®Drug

    Oral administration of CTO daily for 28 day cycles, starting dose of CTO = 219 mg/m2.

    Temodar® administered orally at fixed dose of 150 mg/m2 daily for Days 1-5 in a 28 day cycle.

    Expansion Cohort of 6 patients on fixed dose of 600mg CTO/day Temodar® administered orally at fixed dose of 150 mg/m2 daily for Days 1-5 in a 28 day cycle

  • CTO, Temodar®, Radiation therapyDrug

    Oral administration of CTO daily for 28 day cycles; starting dose of CTO = 219 mg/m2 Temodar® administered orally at a dose of 75 mg/m2 daily during radiation therapy, then at 150mg/m2 for Days 1-5 of Cycle 1, and then up to 200 mg/m2 Days 1-5 of subsequent cycles Radiation: 3-dimensional conformal radiation therapy or, Radiation: intensity-modulated radiation therapy

Study groups in NCT01107522
Study groupRoleWhat they receive
Arm AExperimentalSingle Agent CTO
Receives: Drug: CTO
Arm BExperimentalCombination CTO and Temodar®
Receives: Drug: CTO and Temodar®
Arm CExperimentalCombination CTO, Temodar®, Radiation therapy
Receives: Drug: CTO, Temodar®, Radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To determine the MTD/RD of single agent CTO in patients with advanced or metastatic solid tumors; or CTO in combination with Temodar® in patients with glioblastoma or other recurrent malignant gliomas

    To determine the highest tolerated dose of CTO, based on safety data and occurence of dose-limiting toxicity, in patients with advanced or metastatic solid tumors. In the second stage of the study, to determine the highest tolerated dose of CTO in combination with Temodar®, based on safety data and toxicity profile, in patients with glioblastoma or other recurrent malignant gliomas. In the third stage of the study, to determine the highest tolerated dose of CTO in combination with Temodar® and radiation therapy based on safety data and toxicity profile, in patients with newly diagnosed glioblastoma or other malignant gliomas.

    Measured: Duration of the study

Secondary outcomes (4)

  1. Preliminary tumor response

    RECIST 1.1 (Arm A); Macdonald Criteria (Arms B and C)

    Measured: after every 2 cycles

  2. Pharmacokinetics (maximum concentration, Tmax, AUC, T1/2, clearance, volume of distribution)

    Plasma concentrations and PK parameters will be determined for single agent CTO (Arm A), or CTO in combination with Temodar® (Arm B); plasma concentrations and PK parameters will be determined for Temodar®, or CTO and Temodar® in combination with radiation therapy (Arm C).

    Measured: pre- and post-dose during cycle 1

  3. Voluntary Exploratory objective

    To investigate effect of CTO on tumor growth based on genotype

    Measured: collected prior to enrollment

  4. Exploratory Objective

    To investigate effect of CTO alone and in combination with Temodar® on gene expression in scalp hair

    Measured: Duration of study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Apr 2010 (estimated)
  2. Study startMay 2010
  3. Primary completionJan 2025
  4. Study completionJan 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01107522
Sponsor's protocol ID
T09-10644
Status last verified
Sep 2023
First submitted
16 Apr 2010
Last updated
9 Sep 2025
Results posted
No

Publications

  • Omuro A, Beal K, McNeill K, Young RJ, Thomas A, Lin X, Terziev R, Kaley TJ, DeAngelis LM, Daras M, Gavrilovic IT, Mellinghoff I, Diamond EL, McKeown A, Manne M, Caterfino A, Patel K, Bavisotto L, Gorman G, Lamson M, Gutin P, Tabar V, Chakravarty D, Chan TA, Brennan CW, Garrett-Mayer E, Karmali RA, Pentsova E. Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas. J Clin Oncol. 2018 Jun 10;36(17):1702-1709. doi: 10.1200/JCO.2017.76.9992. Epub 2018 Apr 23.

    PubMed 29683790

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CTO, CTO and Temodar® and CTO, Temodar®, Radiation therapy in people with Solid Tumors, Glioblastoma, Recurrent Malignant Gliomas, run by Tactical Therapeutics, Inc. at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 52 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 9 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To determine the MTD/RD of single agent CTO in patients with advanced or metastatic solid tumors; or CTO in combination with Temodar® in patients with glioblastoma or other recurrent malignant gliomas (time frame: Duration of the study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01107522, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2025.

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