OKN-007 + Temozolomide for Recurrent Brain Cancer

No longer recruiting at 12 trial locations

Overseen By Shinwook Kang

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Oblato, Inc.

Must be taking: Temozolomide

Must not be taking: Bevacizumab

Disqualifiers: Second malignancy, Systemic disorders, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 28-day cycles, up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments, OKN-007 (an experimental treatment) and temozolomide, for individuals with glioblastoma, a severe type of brain cancer that has recurred despite previous treatments. The goal is to determine if this combination is safe and effective in shrinking tumors and slowing disease progression. Suitable participants have glioblastoma that has returned after surgery, radiation, and chemotherapy, with a new tumor identifiable through MRI scans. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot have received any chemotherapeutic agents, including temozolomide, within 28 days before starting the study. It's best to discuss your current medications with the trial team.

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

Research has shown that combining OKN-007 with temozolomide (TMZ) is safe for people with recurrent glioma, a type of brain cancer. Studies have found that OKN-007 remains in the body for an average of 2.8 hours, indicating it is processed quickly. Importantly, previous studies did not identify a dose too high for patients to handle, suggesting good tolerance. Additionally, the combination of OKN-007 and TMZ extended the lifespan of animals compared to TMZ alone, which is promising. While more research is needed to fully understand the safety, the current information is encouraging. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

Researchers are excited about OKN-007 combined with Temozolomide for treating recurrent brain cancer because OKN-007 offers a novel mechanism of action. Unlike standard treatments like surgery, radiation, or chemotherapy alone, OKN-007 works by targeting the tumor microenvironment, which could enhance the effectiveness of Temozolomide, a commonly used chemotherapy drug. This combination has the potential to improve outcomes by not just attacking the cancer cells directly, but also by altering the environment that supports tumor growth, which could reduce recurrence rates and improve survival.

What evidence suggests that OKN-007 combined with temozolomide could be effective for recurrent glioblastoma?

Research shows that combining OKN-007 with temozolomide (TMZ) may help treat recurrent glioblastoma, a type of brain cancer. Studies have found that OKN-007 can shrink tumors and extend patient survival in early tests. When combined with TMZ, a drug already known to prolong life in glioblastoma patients, OKN-007 might enhance treatment effectiveness. Previous research suggests that this combination could improve survival compared to standard treatments. This trial will evaluate the effectiveness of this combination, which may also increase the cancer's responsiveness to TMZ, leading to better outcomes for those with recurring brain cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Shinwook Kang

Principal Investigator

Oblato, Inc.

Are You a Good Fit for This Trial?

Adults with recurrent glioblastoma who've had standard treatment including surgery, radiation, and chemotherapy. They must have good organ function and performance status (able to carry out daily activities), no severe side effects from previous treatments, no more than two prior GBM therapies excluding bevacizumab as second line, and a confirmed diagnosis based on tissue analysis.

Inclusion Criteria

My scans show clear tumor growth, and I have at least one tumor that can be measured.

My glioblastoma was confirmed and I've had specific treatments but not bevacizumab.

I have recovered from side effects of previous treatments.

Exclusion Criteria

Inability to comply with protocol or study procedures

Serious concomitant systemic disorders

Abnormal sodium, potassium, or creatinine levels ≥ grade 2

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive OKN-007 combined with Temozolomide for recurrent glioblastoma

28-day cycles, up to 24 months

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• OKN-007
• Temozolomide

Trial Overview The trial is testing OKN-007 in combination with Temozolomide for safety, effectiveness, and how the body processes it. Participants must show clear signs of tumor recurrence on MRI but should not have received certain other treatments recently or have serious health issues that could interfere.

How Is the Trial Designed?

Group I: All patients Experimental Treatment 2 Interventions

All patients enrolled in this study

Who Is Running the Clinical Trial?

Oblato, Inc.

Lead Sponsor

Trials

5

Recruited

100+

Published Research Related to This Trial

In a phase II trial involving 32 patients with recurrent oligodendroglial tumors, temozolomide (TMZ) demonstrated a 25% objective response rate, indicating its potential as an effective second-line treatment after PCV chemotherapy.

TMZ was generally well tolerated, with hematological side effects being the most common, and a median time to progression of 8 months for those who responded, suggesting it could be a viable option for patients who do not respond to initial treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972. van den Bent, MJ., Chinot, O., Boogerd, W., et al.[2020]

Temozolomide (TMZ) chemotherapy shows a 24% objective response rate in patients with recurrent anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA), with a median progression-free survival of 8.0 months based on a study of 72 patients.

TMZ is recommended as a salvage therapy for recurrent AO/AOA, particularly for patients previously treated with other chemotherapy, as it has an acceptable toxicity profile with severe side effects occurring in only 13% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide salvage chemotherapy for recurrent anaplastic oligodendroglioma and oligo-astrocytoma. Gwak, HS., Yee, GT., Park, CK., et al.[2021]

The study confirmed that the generic temozolomide capsules (TOZ039) are bioequivalent to the brand Temodal® capsules, with pharmacokinetic parameters falling within the acceptable range for both 20-mg and 100-mg doses in 29 patients with brain tumors.

The treatment was found to be safe, with no treatment-related severe adverse events or mortality reported, although 82.8% of patients experienced some adverse effects, highlighting the importance of monitoring patient responses during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence study of 20-mg and 100-mg temozolomide capsules (TOZ309 and Temodal®) in glioma patients in China. Hu, C., Lin, Q., Liu, C., et al.[2021]

In a phase II trial involving 38 patients with recurrent oligodendroglial tumors, temozolomide (TMZ) demonstrated a high response rate, with 52.6% of patients showing a complete or partial response, indicating its efficacy as a first-line chemotherapy.

TMZ was generally well tolerated, with hematologic side effects being the most common, and only one patient discontinuing treatment due to toxicity, suggesting a favorable safety profile for chemotherapy-naive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971. van den Bent, MJ., Taphoorn, MJ., Brandes, AA., et al.[2022]

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]

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]

In a retrospective study of 117 adult patients with recurrent gliomas treated with temozolomide (TMZ) under a compassionate use program, the overall objective response rate was 29%, with 34% achieving disease stabilization, indicating that TMZ is effective in this setting.

The treatment was generally well-tolerated, with mild toxicity; however, thrombocytopenia was the most common serious side effect, occurring in 17% of patients, particularly at higher starting doses, highlighting the importance of monitoring for adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide for the treatment of recurrent supratentorial glioma: results of a compassionate use program in Belgium. Everaert, E., Neyns, B., Joosens, E., et al.[2022]

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]

Citations

1. 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 ...

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. 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 ...

4. withpower.com withpower.com/trial/phase-1-glioblastoma-8-2018-fe4e0

OKN-007 + Temozolomide for Glioblastoma Temozolomide, when used with radiotherapy, has been shown to improve survival in glioblastoma patients, with a two-year survival rate of 26.5% compared to 10.4% ...

5. academic.oup.com academic.oup.com/neuro-oncology/article/23/Supplement_6/vi67/6426342

CTNI-35. UPDATE ON THE FEASIBILITY STUDY OF OKN ... The novel anti-cancer agent OKN-007 plus TMZ increased survival in preclinical studies. Therefore, we initiated a phase Ib/feasibility clinical ...

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

CTNI-35. UPDATE ON THE FEASIBILITY STUDY OF OKN- ... The novel anti-cancer agent OKN-007 plus TMZ increased survival in preclinical studies. Therefore, we initiated a phase Ib/feasibility clinical trial ( ...

7. clinicaltrial.be clinicaltrial.be/en/details/68071?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

OKN-007 in Combination With Adjuvant Temozolomide ... This drug combination is expected to have an anti-cancer effect in patients who have experienced disease progression after first line treatment.

8. 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.