Eflornithine + Temozolomide for Glioblastoma

Recruiting at 7 trial locations

Overseen By Monika Varga

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Orbus Therapeutics, Inc.

Must be taking: Temozolomide

Disqualifiers: Recurrent cancer, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a combination of two drugs, eflornithine (DFMO) and temozolomide, to determine the optimal dose and assess safety and tolerability for treating newly diagnosed brain cancers, specifically glioblastoma and astrocytoma. Participants must have completed a round of radiation therapy and have either glioblastoma or a specific type of astrocytoma. This trial may suit those who have recently finished radiation for these conditions and are already taking temozolomide. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering a chance to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but if you are on corticosteroids, you must be on a stable or decreasing dose. It's best to discuss your specific medications with the trial team.

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

Research is examining the safety and manageability of combining eflornithine and temozolomide for individuals newly diagnosed with glioblastoma, a type of brain cancer. Past patients have demonstrated that this combination can be tolerated, but the exact safe dose remains under investigation.

Eflornithine has been studied for other uses, and temozolomide is already approved for treating certain brain tumors, providing some confidence in their safety. However, since this is an early stage of testing for this specific combination, the primary goal is to determine the right dose and monitor for any possible side effects.

Studies so far suggest that patients can handle the treatment, but ongoing trials must continue to assess its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Eflornithine with Temozolomide for glioblastoma because this approach offers a fresh angle in tackling this aggressive brain cancer. Unlike the standard treatments like surgery, radiation, and chemotherapy with Temozolomide alone, which primarily aim to kill cancer cells, Eflornithine works by inhibiting a specific enzyme called ornithine decarboxylase. This enzyme plays a critical role in cell growth, so blocking it could reduce tumor growth more effectively. By pairing Eflornithine with Temozolomide, researchers hope to enhance the overall effectiveness of the treatment, potentially improving outcomes for patients with glioblastoma.

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

Studies have shown that combining eflornithine with temozolomide can significantly slow the growth of glioblastoma cells, a type of brain cancer. In lab tests, this combination reduced cell growth more effectively than either drug alone. Eflornithine seems to lower the chances of new mutations when paired with temozolomide, potentially preventing the cancer from worsening. Previous research indicates that eflornithine has improved survival rates when combined with other brain tumor treatments. This trial will explore different dose levels of eflornithine with temozolomide to determine the most effective treatment option for glioblastoma. ^{1 6 7 8 9}

Who Is on the Research Team?

Howard Colman, MD, PhD

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Are You a Good Fit for This Trial?

This trial is for adults with a specific brain cancer called glioblastoma (GBM), IDH-wildtype, who have finished radiation therapy and most of their initial chemo with temozolomide. They need good blood, kidney, liver function and agree to use birth control. It's not for those with recent serious heart issues, uncontrolled diabetes or other cancers, active infections, prior Optune treatment or poorly controlled seizures.

Inclusion Criteria

I have finished my external beam radiation therapy as recommended.

I took at least 80% of my prescribed TMZ doses during my treatment.

Willing to abstain from intercourse or use acceptable contraceptive methods

Exclusion Criteria

I have previously been treated with Optune.

I do not have any serious infections or illnesses right now.

Use of another investigational agent within 30 days of enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive escalating doses of eflornithine plus temozolomide, followed by an expansion cohort to evaluate safety and preliminary efficacy

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Survival Follow-Up

Participants are monitored for overall survival up to 2 years after the last treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Eflornithine
• Temozolomide

Trial Overview The study tests different doses of Eflornithine in combination with Temozolomide to find the safest and most effective dose for treating newly diagnosed GBM patients. The goal is also to check how well patients tolerate this drug combo.

How Is the Trial Designed?

Group I: Eflornithine Dose Level 2 + Temozolomide Experimental Treatment 2 Interventions

Group II: Eflornithine Dose Level 1 + Temozolomide Experimental Treatment 2 Interventions

Group III: Eflornithine Dose Level -1 + Temozolomide Experimental Treatment 2 Interventions

Eflornithine is already approved in European Union, United States for the following indications:

Approved in European Union as Vaniqa for:

• Hirsutism
• African trypanosomiasis

Approved in United States as Vaniqa for:

• Hirsutism

Approved in United States as Iwilfin for:

• High-risk neuroblastoma

Who Is Running the Clinical Trial?

Orbus Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

410+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7646829/

Effect of eflornithine on mutation frequency in temozolomide ... It was shown that TMZ significantly increased the frequency of mutations in U87MG glioblastoma cells while DFMO-treated cells showed mutation ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05879367

Study Details | NCT05879367 | Evaluation of Eflornithine ... The purpose of this study is to establish the recommended phase 2 dose of eflornithine in combination with temozolomide in patients whose glioblastoma or ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30941997/

Combination treatment for glioblastoma with temozolomide ... Results: The combination treatment resulted in a consistent higher suppression of proliferation in all cell lines treated and induced a significant higher cell ...

4. jbuon.com jbuon.com/archive/24-1-397.pdf

Combination treatment for glioblastoma with temozolomide ... In conclusion, we believe that the combina- tion of TMZ, DFMO and radiotherapy constitutes a promising therapy for GBM, mainly because both.

5. orbustherapeutics.com orbustherapeutics.com/product-candidate

Late stage brain tumor clinical trial. AA3 Eflornithine and lomustine achieved a clinically meaningful improvement in overall survival (OS) and progression free survival (PFS) compared to lomustine as a ...

6. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2022-0990.html

An open-label, Phase 1b study to evaluate the safety and ... An open-label, Phase 1b study to evaluate the safety and tolerability of eflornithine plus temozolomide in patients with newly diagnosed glioblastoma.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5977277/

Clinical importance of eflornithine (α-difluoromethylornithine ... This paper summarizes the results of all published studies of eflornithine for the treatment of gliomas, and provides most recent updates.

8. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/eflornithine?pn=1

Clinical Trials Using Eflornithine - NCI Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma or Astrocytoma. Status: Active. Location: 5 locations. Eflornithine ...

9. cancer.columbia.edu cancer.columbia.edu/cancer-types-care/clinical-trials/find-clinical-trial/open-label-phase-1b-study-evaluate-safety-andtolerability-eflornithine-plus-temozolomide-patients-newly-diagnosed-glioblastoma-or-astrocytoma

An open-label, Phase 1b study to evaluate the safety ... The purpose of this study is to measure how safe eflornithine is in combination with temozolomide in patients with newly diagnosed glioblastoma multiforme ...