NG101m Adjuvant Therapy for Glioblastoma

Overseen By Thien Tran, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: NeuGATE Theranostics

Must be taking: Temozolomide

Must not be taking: Corticosteroids

Disqualifiers: Pregnancy, Breastfeeding, Immunodeficiency, Autoimmune, 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

52 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not be on any alternative therapies. If you are on corticosteroid therapy, it must be reduced to a low dose.

What data supports the effectiveness of the treatment NG101m Adjuvant Therapy for Glioblastoma?

Research shows that combining temozolomide (a chemotherapy drug) with radiation therapy can be effective for treating high-grade brain tumors like glioblastoma. In studies, this combination has shown improved response rates and quality of life in patients with brain metastases from other cancers, suggesting potential benefits for glioblastoma as well. ^{1 2 3 4 5}

Is NG101m (Temozolomide) safe for humans?

Temozolomide is generally well tolerated and safe, with common side effects like fatigue, nausea, and vomiting. However, severe blood-related side effects, such as myelodysplastic syndrome and aplastic anemia, have been rarely reported. ^{2 3 6 7 8}

How is the NG101m Adjuvant Therapy for Glioblastoma treatment different from other treatments?

The NG101m Adjuvant Therapy combines intensity-modulated radiation therapy (IMRT) with temozolomide (TMZ), a drug that helps make cancer cells more sensitive to radiation, which is now a standard approach for newly diagnosed glioblastoma. This combination is unique because it uses TMZ as a radiosensitizer, potentially enhancing the effectiveness of radiation therapy. ^{2 5 8 9 10}

What is the purpose of this trial?

This trial tests if adding NG101m capsules to standard brain cancer treatments can help patients with newly diagnosed glioblastoma multiforme live longer. NG101m is expected to make chemotherapy and radiation more effective.

Research Team

Yvonne Kew, MD, PhD

Principal Investigator

NeuGATE Theranostics

Eligibility Criteria

This trial is for adults over 18 with newly diagnosed glioblastoma who are set to start chemoradiation therapy. They must have certain blood and organ function levels, not be pregnant or breastfeeding, and can't be on other therapies or have specific allergies or diseases like immunodeficiency or autoimmune disorders.

Inclusion Criteria

BUN ≤ 1.5 times upper limit of normal

Platelet count 100,000/mm3

My main treatment is a combination of chemotherapy and radiation.

Exclusion Criteria

I cannot reduce my steroid medication to a low dose.

Known hypersensitivity to meloxicam, famotidine, and/or caffeine or any of their derivatives or components

Pregnant women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Chemotherapy

Participants receive radiation therapy of 60 Gray (Gy) with concomitant oral temozolomide (TMZ) and NG101m for 6 weeks

6 weeks

Adjuvant Therapy

Participants continue with six cycles of high-dose temozolomide and NG101m

6 months

Follow-up

Participants are monitored for safety, tolerability, and effectiveness after treatment

24 months

Treatment Details

Interventions

• Intensity-modulated radiation therapy
• NG101m
• Temozolomide

Trial Overview The trial tests NG101m capsules as an add-on to the standard glioblastoma treatment, which includes temozolomide chemotherapy and intensity-modulated radiation therapy. The goal is to see if adding NG101m improves outcomes.

Participant Groups

Group I: NG101m and standard treatment Experimental Treatment 3 Interventions

Concomittant therapy: Radiation therapy, oral temozolomide, and oral NG101m Adjuvant therapy: Oral temozolomide and oral NG101m

Intensity-modulated radiation therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as IMRT for:

• Rectal cancer
• Gastrointestinal cancers
• Gynecologic cancers
• Central nervous system tumors
• Spinal tumors
• Head and neck malignancies
• Thoracic malignancies
• Abdominal malignancies
• Pelvic malignancies

Approved in United States as IMRT for:

• Rectal cancer
• Gastrointestinal cancers
• Gynecologic cancers
• Central nervous system tumors
• Spinal tumors
• Head and neck malignancies
• Thoracic malignancies
• Abdominal malignancies
• Pelvic malignancies

Approved in Canada as IMRT for:

• Rectal cancer
• Gastrointestinal cancers
• Gynecologic cancers
• Central nervous system tumors
• Spinal tumors
• Head and neck malignancies
• Thoracic malignancies
• Abdominal malignancies
• Pelvic malignancies

Approved in Japan as IMRT for:

• Rectal cancer
• Gastrointestinal cancers
• Gynecologic cancers
• Central nervous system tumors
• Spinal tumors
• Head and neck malignancies
• Thoracic malignancies
• Abdominal malignancies
• Pelvic malignancies

Approved in China as IMRT for:

• Rectal cancer
• Gastrointestinal cancers
• Gynecologic cancers
• Central nervous system tumors
• Spinal tumors
• Head and neck malignancies
• Thoracic malignancies
• Abdominal malignancies
• Pelvic malignancies

Approved in Switzerland as IMRT for:

• Rectal cancer
• Gastrointestinal cancers
• Gynecologic cancers
• Central nervous system tumors
• Spinal tumors
• Head and neck malignancies
• Thoracic malignancies
• Abdominal malignancies
• Pelvic malignancies

Who Is Running the Clinical Trial?

NeuGATE Theranostics

Lead Sponsor

Trials

1

Recruited

50+

Findings from Research

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 study of 9 patients with brain metastases from lung adenocarcinoma, the combination of intensity-modulated radiation therapy (IMRT) and temozolomide (TMZ) resulted in a high objective response rate of 77.8%, with one complete response and six partial responses, confirming the efficacy of this treatment approach.

Patients receiving the combination treatment experienced fewer severe adverse effects compared to those who only received IMRT, with no grade ≥3 hematologic toxicities reported, and an improvement in quality of life was noted, indicating that the addition of TMZ is both effective and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy combined with concomitant temozolomide for brain metastases from lung adenocarcinoma. Li, J., Chai, X., Cao, Y., et al.[2020]

Temozolomide (TMZ) is commonly used as an adjuvant therapy for malignant glioma, but in this case study, a patient developed treatment-related acute myeloid leukemia (t-AML) after receiving 15 cycles of TMZ, highlighting a rare but serious complication.

The case raises questions about the duration of TMZ therapy, as the patient showed no tumor progression but still developed t-AML, suggesting a need for better guidelines to balance treatment benefits and risks in long-term TMZ use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma. Kosugi, K., Saito, K., Takahashi, W., et al.[2018]

In a study of 27 patients with newly diagnosed high-grade gliomas, the combination of temozolomide (TMZ) and radiation therapy (RT) demonstrated promising efficacy, with a median overall survival of 19 months and a one-year survival rate of 81.2%.

The treatment was well tolerated with no drug toxicity-related mortality, indicating a favorable safety profile, especially in patients under 50 years old and those who had debulking surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The outcomes of concomitant radiation plus temozolomide followed by adjuvant temozolomide for newly diagnosed high grade gliomas: the preliminary results of single center prospective study. Shawky, H., Abo Hamar, AH., Galal, S., et al.[2020]

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) can cause severe drug-induced toxic hepatitis, as demonstrated in a case where a patient developed significant liver issues after 5 weeks of treatment for glioblastoma, highlighting the importance of monitoring liver function during therapy.

To prevent serious complications, including potentially life-threatening conditions, it is crucial to monitor liver enzyme levels twice weekly during TMZ treatment and to discontinue the drug immediately if hepatitis is suspected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-induced liver damage. A case report. Becker, F., Hecht, M., Schmidtner, J., et al.[2021]

In a study of 51 patients with newly diagnosed glioblastoma, concurrent treatment with temozolomide (TMZ) and radiotherapy was found to be the new standard of care.

The occurrence of early necrosis in 14% of patients, without signs of tumor recurrence, suggests that TMZ may enhance the effectiveness of radiotherapy by acting as a radiosensitizer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. Chamberlain, MC., Glantz, MJ., Chalmers, L., et al.[2022]

References

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

Future directions for temozolomide therapy. [2019]

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

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

3. Greece pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy combined with concomitant temozolomide for brain metastases from lung adenocarcinoma. [2020]

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

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma. [2018]

5. England pubmed.ncbi.nlm.nih.gov

The outcomes of concomitant radiation plus temozolomide followed by adjuvant temozolomide for newly diagnosed high grade gliomas: the preliminary results of single center prospective study. [2020]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Temozolomide-related hematologic toxicity. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Temozolomide-induced liver damage. A case report. [2021]

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

Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Bone morphogenetic protein 7 sensitizes O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide. [2018]