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

27 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug 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% with radiotherapy alone. It is effective in treating various brain tumors and has been approved for initial management of glioblastoma. ^{1 2 3 4 5}

Is the combination of OKN-007 and Temozolomide safe for humans?

Temozolomide is generally well tolerated, with common side effects like fatigue, nausea, and vomiting. However, it can cause serious blood-related issues like thrombocytopenia (low platelet count) and, rarely, conditions like aplastic anemia (a condition where the body stops producing enough new blood cells). ^{1 4 6 7 8}

What makes the OKN-007 + Temozolomide treatment for glioblastoma unique?

The OKN-007 + Temozolomide treatment for glioblastoma is unique because it combines Temozolomide, an oral drug that has shown effectiveness in improving survival when used with radiotherapy, with OKN-007, which may offer additional benefits. This combination is being explored to enhance the effectiveness of treatment for glioblastoma, a type of brain cancer, by potentially improving outcomes beyond what Temozolomide alone can achieve. ^{1 2 4 5 9}

What is the purpose of this trial?

This trial is testing if adding the drug OKN-007 to the standard treatment with Temozolomide and radiotherapy can help patients with malignant Glioblastoma, especially those whose cancer has gotten worse after initial treatment. Temozolomide has become a cornerstone in the treatment of glioblastoma, often used in combination with radiotherapy.

Research Team

James Battiste, MD

Principal Investigator

Principal Investigator

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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 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]

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 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 (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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of temozolomide in patients with progressive low-grade glioma. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. [2019]

3. France pubmed.ncbi.nlm.nih.gov

[What type of adjuvant chemotherapy should be proposed for the initial treatment of glioblastoma?]. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

A phase I dose-escalation study (ISIDE-BT-1) of accelerated IMRT with temozolomide in patients with glioblastoma. [2018]

5. Japan pubmed.ncbi.nlm.nih.gov

[Temozolomide: Temodal]. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Phase I trial of temozolomide (NSC 362856) in patients with advanced cancer. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Temozolomide-related hematologic toxicity. [2018]

9. Cyprus pubmed.ncbi.nlm.nih.gov

Benefit and outcome of using temozolomide-based chemoradiotherapy followed by temozolomide alone for glioblastoma in clinical practice. [2019]