CTO + Temodar® for Glioblastoma

Not currently recruiting at 3 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called carboxyamidotriazole orotate (CTO) for certain brain tumors, such as glioblastoma. The main goal is to assess the safety and tolerability of CTO, both alone and in combination with Temodar® (an oral chemotherapy drug) and possibly radiation therapy. The study seeks patients with advanced brain tumors who have not responded to other treatments. Participants should have measurable tumors on MRI scans and, if applicable, have undergone previous radiation treatment. This trial may suit those experiencing tumor progression despite standard therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot take medications that are known CYP3A4 inhibitors or inducers. If you are on anti-epileptic drugs, they must not be CYP3A4 inhibitors or inducers, and you should be on a stable dose for at least 2 weeks.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that carboxyamidotriazole orotate (CTO) is generally safe for use alone or with other cancer treatments. In earlier studies, CTO proved safe for patients with advanced tumors, with doses ranging from 75 to 427 mg/m² per day causing no serious side effects. Another study demonstrated that CTO was well-tolerated when combined with Temodar® (a chemotherapy drug), with no severe side effects reported, making it a promising option for those with glioblastoma, a type of brain cancer.

When combined with Temodar® and radiation therapy, CTO remains safe and manageable. The most common side effects were mild, such as nausea and tiredness. Overall, these findings suggest that CTO, whether used alone or with other treatments, has an acceptable safety profile for cancer patients.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for glioblastoma because they explore new ways to enhance effectiveness against this aggressive brain cancer. Carboxyamidotriazole Orotate (CTO) is a unique compound that disrupts cancer cell signaling, potentially slowing tumor growth. When combined with Temodar®, a chemotherapy standard, or paired with radiation therapy, there's hope these combinations might boost overall treatment efficacy. Unlike traditional treatments that mainly rely on Temodar® alone, these new approaches could offer a more comprehensive attack on the cancer cells, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

Research has shown that Carboxyamidotriazole Orotate (CTO) may help treat brain cancers. In one study, 67% of patients benefited from the treatment, and 26% experienced a noticeable improvement. Some patients even had a complete response, significantly improving their cancer symptoms. In this trial, participants in Arm A will receive CTO as a single agent.

In Arm B, participants will receive a combination of CTO and Temodar®, which is generally well tolerated and may improve survival rates for glioblastoma patients. Arm C will explore the combination of CTO, Temodar®, and radiation therapy. Temodar® alone is already known to help when used with radiation, so these combinations could be even more effective. These findings suggest that using CTO with Temodar® might offer new hope for treating glioblastoma.12678

Who Is on the Research Team?

Matthew H. Taylor, MD | Portland, OR

Matthew Taylor, MD

Principal Investigator

Oregon Health and Sciences University

Walter Urba - Providence

Walter Urba, MD, PhD

Principal Investigator

Providence Health & Services

KM

Katharine McNeill, MD

Principal Investigator

NYU MEDICAL CENTER

TC

Timothy Chan, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

EP

Elena Pentsova, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

LD

Lisa DeAngelis, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with certain brain tumors (glioblastoma or malignant gliomas) that are new, recurring, or have not responded to standard treatments. Participants must be in good health otherwise, with proper liver and kidney function, and cannot be pregnant or breastfeeding. They should not have other recent cancers (except some skin cancers and localized breast/cervix cancers), uncontrolled illnesses like heart disease or diabetes, active infections, HIV/HBV/HCV infection, a high risk of bleeding, psychiatric disorders affecting compliance, or be on specific drugs affecting the liver enzyme CYP3A4.

Inclusion Criteria

Requirements for being included in Treatment Arm A.
Your bone marrow must be functioning properly, which means you need to have enough neutrophils and platelets in your blood.
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.
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Exclusion Criteria

Active infection.
Unstable diabetes mellitus.
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.
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Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CTO as a single agent or in combination with Temodar® and radiation therapy to determine the maximum tolerated dose

Duration of the study
Pre- and post-dose visits during cycle 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Exploratory Objective

Investigate the effect of CTO on gene expression and tumor growth

Duration of study

What Are the Treatments Tested in This Trial?

Interventions

  • Carboxyamidotriazole Orotate (CTO)
  • Radiation therapy
  • Temodar®
Trial Overview The trial is testing Carboxyamidotriazole Orotate (CTO) alone for advanced solid tumors; combined with Temodar® for recurrent brain tumors; and together with Temodar® plus radiation therapy for newly diagnosed brain tumors. The goal is to find the safest dose that can be tolerated without causing severe side effects.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Group I: Arm CExperimental Treatment1 Intervention
Group II: Arm BExperimental Treatment1 Intervention
Group III: Arm AExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Tactical Therapeutics, Inc.

Lead Sponsor

Trials
3
Recruited
130+

Published Research Related to This Trial

Temodar is a promising new drug for treating brain tumors and other cancers, currently being researched for its effectiveness against solid tumors, glioblastoma multiforme, and metastatic melanoma.
It offers adult patients with anaplastic astrocytoma a convenient treatment option with minimal side effects, providing hope for better outcomes.
Temodar offers promise for treating astrocytomas.Armstrong, T., Hancock, C.[2018]
Temozolomide (TMZ) is an effective oral treatment for recurrent glioblastoma multiforme, showing nearly 100% bioavailability and a favorable safety profile, making it a promising option for patients with this aggressive brain cancer.
Research is ongoing to enhance the efficacy of TMZ by combining it with other treatments like chemotherapy, radiation, and immunotherapy, as well as exploring alternative dosing strategies to overcome resistance in gliomas.
Future directions in the treatment of malignant gliomas with temozolomide.Prados, MD.[2018]
Temozolomide (TMZ) is the only anticancer drug proven to improve survival in glioblastoma when used with radiotherapy, showing high concentrations in brain tumors and cerebrospinal fluid, which enhances its effectiveness.
Molecular markers like MGMT promoter methylation can predict better responses to TMZ treatment, but side effects such as myelosuppression and nausea are common, necessitating precautions like prophylaxis against Pneumocystis carinii pneumonia.
[Temozolomide: Temodal].Shinoura, N., Yamada, R., Tabei, Y., et al.[2018]

Citations

Multicenter Phase IB Trial of Carboxyamidotriazole Orotate ...Results. Forty-seven patients were enrolled. Treatment was well tolerated; toxicities included fatigue, constipation, nausea, and hypophosphatemia.
Study Details | NCT01107522 | Safety and Tolerability of ...The purpose of this study is to determine the safety, tolerability, and the maximum tolerated dose/recommended phase II dose of carboxyamidotriazole orotate ...
Abstract LB081: Carboxyamidotriazole orotate (CTO) with ...Addition of CTO to TMZ or TMZ/RT respectively was safe with no DLT. Survival in both recurrent HGG and newly diagnosed GBM patients compares favorably with ...
Multicenter Phase IB Trial of Carboxyamidotriazole Orotate ...Treatment was well tolerated; toxicities included fatigue, constipation, nausea, and hypophosphatemia. Pharmacokinetics showed that CTO did not ...
Phase IB trial of carboxyamidotriazole orotate (CTO) and ...Phase IB trial of carboxyamidotriazole orotate (CTO) and radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ) in newly diagnosed glioblastoma (GBM) ...
Carboxyamidotriazole orotate in glioblastomaCombined treatment with carboxyamidotriazole orotate (CTO) and temozolomide has an acceptable safety profile and encouraging activity in patients with ...
Phase IB trial of carboxyamidotriazole orotate (CTO) and ...... temozolomide (TMZ) in newly diagnosed glioblastoma (GBM). Phase IB trial of ... Conclusions: CTO in combination with RT and TMZ is safe and well tolerated.
Carboxyamidotriazole orotate (CTO) in combination with ...2067. Background: BEV is approved for the treatment of recurrent glioblastoma pts, but there is a lack of effective therapies once a tumor recurs on BEV.
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