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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NG101m for individuals with glioblastoma, a type of brain cancer. The aim is to determine if adding NG101m to standard treatments, such as intensity-modulated radiation therapy and the drug temozolomide, can enhance cancer treatment effectiveness. Participants will receive the new therapy alongside the usual treatments. Those newly diagnosed with glioblastoma and undergoing chemotherapy and radiation may be suitable for this study. 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 therapy.

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.

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

Research shows that NG101m is undergoing tests for safety and effectiveness in treating glioblastoma alongside standard treatments like temozolomide and radiation. Previous studies have found temozolomide to be generally well-tolerated, with common side effects such as tiredness, nausea, and vomiting, which are typically not severe. As NG101m is in early-phase trials, researchers are closely monitoring its safety in humans. Reaching this trial phase suggests some confidence in its potential safety. It is important to consult a healthcare provider to understand the risks and benefits for your specific situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NG101m for glioblastoma because it introduces a novel component to the existing treatment regimen. Unlike standard treatments that typically involve radiation and temozolomide alone, NG101m adds an additional oral therapy that may enhance the effectiveness of these traditional options. This new approach could potentially target the tumor more effectively and improve patient outcomes. By combining NG101m with existing therapies, there is hope for a synergistic effect that could slow tumor progression more successfully than current methods.

What evidence suggests that NG101m adjuvant therapy might be an effective treatment for glioblastoma?

Research has shown that combining the drug temozolomide with radiation therapy helps glioblastoma patients live longer. Studies indicate that this combination can increase the 10-year survival rate to 70%, compared to 47% with just radiation. In this trial, participants will receive NG101m in addition to standard treatments, including temozolomide and radiation therapy. Early trials are investigating whether NG101m can extend survival for glioblastoma patients when added to these standard treatments. The aim is to determine if NG101m can improve the 2-year survival rate, currently about 27.2% for newly diagnosed patients. Researchers are testing NG101m with standard treatment to assess its potential to extend survival times. ^{1 2 3 4 5}

Who Is on the Research Team?

Yvonne Kew, MD, PhD

Principal Investigator

NeuGATE Theranostics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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 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]

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04373785

Study Details | NCT04373785 | NG101m Adjuvant Therapy ... Efficacy of NG101m adjuvant therapy will be assessed by measuring 2-year overall survival rate. 24 months. Secondary Outcome Measures ...

2. trial.medpath.com trial.medpath.com/clinical-trial/e6930351be3e932b/nct04373785-multi-center-clinical-trial-ng101m-glioblastoma

NG101m Adjuvant Therapy in Glioblastoma Patients - MedPath The median survival rate for newly diagnosed GBM patients is 14.6 months with a 2-year overall survival (OS) rate of 27.2%. This clinical trial evaluates the 2- ...

3. withpower.com withpower.com/trial/phase-2-glioblastoma-2022-add60

NG101m Adjuvant Therapy for Glioblastoma This trial tests if adding NG101m capsules to standard brain cancer treatments can help patients with newly diagnosed glioblastoma multiforme live longer.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10764117/

Investigational Treatment Strategies in Glioblastoma: Progress ... Efforts to develop more effective treatments have yielded only marginal change to survival rates with multimodal therapies. At present, upfront maximal safe ...

5. meghan-johnson-scholarship-fund.clinicaltrialconnect.com meghan-johnson-scholarship-fund.clinicaltrialconnect.com/trials/NCT04373785

NG101m Adjuvant Therapy in Glioblastoma Patients - Meghan M ... The purpose of this clinical trial is to evaluate the addition of NG101m adjuvant therapy to standard of care treatment of glioblastoma multiforme. All subjects ...