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

NCT01107522 | Unknown Phase 1

• 1 other identifier: T09-10644
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

Brief 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 malignant gliomas; or in combination with oral Temodar® and radiation therapy in patients with newly diagnosed glioblastoma or other malignant gliomas.

Conditions

Solid Tumors, Glioblastoma, Recurrent Malignant Gliomas

Outcome Measures

Primary Outcomes (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.

  Duration of the study

Secondary Outcomes (4)

• Preliminary tumor response

  after every 2 cycles

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

  pre- and post-dose during cycle 1

• Voluntary Exploratory objective

  collected prior to enrollment

• Exploratory Objective

  Duration of study

Study Arms (3)

Arm A

EXPERIMENTAL

Single Agent CTO

Drug: CTO

Arm B

EXPERIMENTAL

Combination CTO and Temodar®

Drug: CTO and Temodar®

Arm C

EXPERIMENTAL

Combination CTO, Temodar®, Radiation therapy

Drug: CTO, Temodar®, Radiation therapy

Interventions

CTO DRUG

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

Arm A

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

Arm B

CTO, Temodar®, Radiation therapy DRUG

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

Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Tactical Therapeutics, Inc.: lead

Study Sites (4)

New York University

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10017, United States

Location

Providence Cancer Center

Portland, Oregon, 97213, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• 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.

  PMID: 29683790 DERIVED

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Matthew Taylor, MD

  Oregon Health and Sciences University

  PRINCIPAL INVESTIGATOR

• Elena Pentsova, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Walter Urba, MD, PhD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

• Katharine McNeill, MD

  NYU MEDICAL CENTER

  PRINCIPAL INVESTIGATOR

• Lisa DeAngelis, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Timothy Chan, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2010
• First Posted: April 21, 2010
• Study Start: May 1, 2010
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2026
• Last Updated: September 9, 2025

Record last verified: 2023-09

Locations

US (4)