OKN-007 + Temozolomide for Glioblastoma

Overseen By Ingrid Block, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Oklahoma

Disqualifiers: Second malignancy, Renal impairment, Cardiac disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding a new drug, OKN-007, to the standard treatment with Temozolomide can help combat glioblastoma, an aggressive brain cancer. Researchers aim for this combination to be more effective for those whose cancer has worsened after initial treatment. Participants will receive radiotherapy (Photon/Proton IMRT) along with one of two dosing schedules of OKN-007 and Temozolomide. This trial may suit individuals newly diagnosed with glioblastoma who have undergone surgery to remove the tumor and are recovering well. 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 drug.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research shows that using OKN-007 with Temozolomide appears safe for patients. Studies have found that this treatment is generally well-tolerated, even at higher doses. For instance, one study involved patients with recurrent glioma receiving OKN-007, and they did not reach a dose that was too high, indicating safety. Another study suggested that this combination might lead to better results than some standard treatments.

In animal studies, this combination helped mice with glioma live longer compared to using Temozolomide alone. While these findings are encouraging, ongoing human trials continue to gather more information about safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining OKN-007 with temozolomide for glioblastoma because this treatment offers a potentially new mechanism of action. Unlike traditional therapies that primarily focus on killing cancer cells, OKN-007 targets the tumor's microenvironment, which could inhibit tumor growth more effectively. The treatment regimen includes both three-day and five-day weekly doses of OKN-007, offering flexibility and the potential for more tailored patient care. Additionally, this combination with the standard chemotherapy drug, temozolomide, might enhance the overall effectiveness against glioblastoma, giving hope for better outcomes in this aggressive cancer.

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

Research shows that using OKN-007 with Temozolomide might help treat glioblastoma, a type of brain cancer. In this trial, participants will receive OKN-007 either three days per week or five days per week, both in combination with Temozolomide. Studies have found that OKN-007 can make cancer cells more responsive to Temozolomide, potentially resulting in smaller tumors and longer survival times. Earlier trials demonstrated that this combination was safe and could lead to better outcomes than standard treatments. Specifically, evidence suggests it might extend the lives of people with recurring glioma. These findings offer hope that this combination could be effective for patients whose disease is worsening. ^{1 3 4 5 6}

Who Is on the Research Team?

James Battiste, MD

Principal Investigator

Principal Investigator

Are You a Good Fit for This Trial?

Adults with newly diagnosed Glioblastoma who've had surgery can join this trial. They need to provide tumor tissue, have a performance status of 0-2, and good organ function. Men must use contraception and not donate sperm for 120 days post-treatment. Women of childbearing potential must test negative for pregnancy and use birth control.

Inclusion Criteria

I had surgery to remove my brain tumor within the last 7 weeks.

Birth control should be used from the signing of the patient consent form and for 120 days following the last dose of study treatment

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

Screening ECG abnormality documented by the investigator as medically significant

Inability to comply with protocol or study procedures

I have no other cancers except for treated skin cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive OKN-007 and Temozolomide in combination with radiotherapy. OKN-007 is administered 3 or 5 times a week, Temozolomide is taken daily for 42 days, and radiotherapy is given in 30 fractions.

6 weeks

Follow-up

Participants are monitored for safety, effectiveness, and progression-free survival after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• OKN-007
• Photon/Proton IMRT
• Temozolomide

Trial Overview The study tests OKN-007 combined with Temozolomide chemotherapy alongside standard radiotherapy in patients with Glioblastoma to see if it improves outcomes after initial treatment failure.

How Is the Trial Designed?

Group I: OKN-007 5 days per week and temozolomide Experimental Treatment 3 Interventions

OKN-007: 60 mg/kg, IV, 5 times a week Temozolomide: 75 mg/m2, oral, once daily for 42 days Radiotherapy: 60 Gy administered in 30 fractions

Group II: OKN-007 3 days per week plus temozolomide Experimental Treatment 3 Interventions

OKN-007: 60 mg/kg, IV, 3 times a week Temozolomide: 75 mg/m2, oral, once daily for 42 days Radiotherapy: 60 Gy administered in 30 fractions

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Published Research Related to This Trial

Carmustine wafers (Gliadel) and temozolomide (Temodal) have been approved for treating glioblastoma, with temozolomide showing a median survival benefit of 2 months when used with radiotherapy, and a two-year survival rate of 26.5% compared to 10.4% with radiotherapy alone.

In patients who undergo complete tumor resection, the two-year survival rate can reach 38%, highlighting the potential effectiveness of these treatments in younger patients with good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[What type of adjuvant chemotherapy should be proposed for the initial treatment of glioblastoma?]. Ducray, F., Honnorat, J.[2018]

In a phase II trial involving 46 patients with progressive low-grade glioma, Temozolomide (Temodar) demonstrated a 61% objective response rate, with 24% achieving complete response and 37% achieving partial response.

The treatment showed promising safety, with limited toxicity observed; however, one patient experienced severe complications, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of temozolomide in patients with progressive low-grade glioma. Quinn, JA., Reardon, DA., Friedman, AH., et al.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Temozolomide: Temodal]. Shinoura, N., Yamada, R., Tabei, Y., et al.[2018]

In a Phase I clinical trial involving 19 patients with glioblastoma, the maximum tolerated dose of fractionated intensity-modulated radiotherapy (IMRT) combined with temozolomide (TMZ) was determined to be 65 Gy, delivered in 25 fractions over 5 weeks, without any dose-limiting toxicities observed.

The treatment was well tolerated, with only mild to moderate (Grade 1-2) neurologic and skin toxicities reported, and no severe late neurologic toxicities, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose-escalation study (ISIDE-BT-1) of accelerated IMRT with temozolomide in patients with glioblastoma. Morganti, AG., Balducci, M., Salvati, M., et al.[2018]

Temozolomide (TMZ) is generally safe with mild to moderate side effects, but this case report highlights a rare instance of severe aplastic anemia (AA) in a 68-year-old female patient following treatment for glioblastoma, indicating a potential serious risk associated with the drug.

The patient's AA was managed successfully with supportive care, including platelet transfusions and growth factor treatment, and her blood counts returned to normal within 38 days, emphasizing the importance of monitoring blood parameters during and after TMZ treatment to detect such rare toxicities early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. Gilbar, PJ., Pokharel, K., Mangos, HM.[2022]

Temozolomide (TMZ) is an effective oral treatment for malignant gliomas, providing significant survival benefits while being generally well tolerated by patients.

While most side effects of TMZ are mild to moderate, there is a risk of severe hematologic adverse events, such as myelodysplastic syndrome and aplastic anemia, which have been documented in the literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-related hematologic toxicity. Scaringi, C., De Sanctis, V., Minniti, G., et al.[2018]

Temozolomide (TMZ) is well tolerated in patients with glioma and melanoma, with dose-limiting toxicity primarily being thrombocytopenia, observed at maximum tolerated doses of 150 mg/m2/day for patients with prior nitrosourea exposure and 250 mg/m2/day for those without.

The study showed promising antitumor activity, with two complete responses in patients without prior nitrosourea treatment, suggesting that TMZ could be an effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of temozolomide (NSC 362856) in patients with advanced cancer. Dhodapkar, M., Rubin, J., Reid, JM., et al.[2018]

Temozolomide is primarily used for treating refractory central nervous system cancers like anaplastic astrocytoma and glioblastoma, but ongoing clinical trials are exploring its efficacy and safety in newly diagnosed gliomas and other types of tumors.

Research is also investigating different dosing schedules and combinations with other treatments, suggesting that temozolomide could be a versatile option in cancer therapy beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. Yung, WK.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8598781/

CTNI-35. UPDATE ON THE FEASIBILITY STUDY OF OKN- ... The treatment plan appears safe and well-tolerated at the Cohort A combination dosing level and may increase favorable treatment outcomes suggesting that the ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04388475

Open-label Study Investigating of OKN-007 Combined With ... This is a phase II open-label study investigating the efficacy, safety and pharmacokinetic(PK) properties of OKN-007 combined with temozolomide(TMZ) in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6251232/

OKN-007 Increases temozolomide (TMZ) Sensitivity and ... We have assessed a novel nitrone-based agent, OKN-007, and found it to be effective in decreasing tumor volumes and increasing survival in ...

4. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT201/742318/Abstract-CT201-Phase-2-clinical-trial-of-OKN-007

Phase 2 clinical trial of OKN-007 in recurrent malignant glioma Our data indicate that the combination therapy of OKN-007 and TMZ appears safe and, compared to standard lomustine therapy, may prolong OS in rGBM.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.2538

Phase Ib clinical trial of OKN-007 in recurrent malignant ... Our data suggest that, compared to standard therapy, OKN-007 may prolong OS in recurrent glioma. Based on new data, a trial of OKN-007 plus ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7650353/

CTNI-16. FEASIBILITY PILOT STUDY OF OKN-007 IN ... The novel anti-cancer agent OKN-007 plus TMZ increased survival in glioma-bearing mice compared to TMZ alone.