Chemoradiation for Glioblastoma

(NeoGlio Trial)

Recruiting at 1 trial location

Overseen By Karen Hassanzadeh

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Geisinger Clinic

Must not be taking: Temozolomide

Disqualifiers: Recurrent gliomas, Distant disease, Pregnancy, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that prior chemotherapy for a different cancer is allowed, except for temozolomide. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Temozolomide in treating glioblastoma?

Research shows that Temozolomide, when used with radiation therapy, improves survival in patients with glioblastoma. It is effective for treating various brain tumors, including newly diagnosed and recurrent gliomas. ^{1 2 3 4 5}

Is chemoradiation with temozolomide generally safe for humans?

Temozolomide, used in chemoradiation, is generally well-tolerated but can cause side effects like low blood platelet counts (thrombocytopenia), fatigue, nausea, and vomiting. Rarely, it may cause liver damage, so monitoring is important during treatment. ^{1 5 6 7 8}

What makes the drug Temozolomide unique for treating glioblastoma?

Temozolomide is unique because it is an oral drug that improves survival in glioblastoma when used with radiotherapy, and it has a favorable toxicity profile compared to other treatments. It works by converting into an active form that targets cancer cells, and it is effective for various brain tumors, including gliomas and brain metastases. ^{1 4 5 9 10}

What is the purpose of this trial?

Preoperative therapy has not been well studied in resectable glioblastoma. This study attempts to prospectively assess the feasibility and efficacy of preoperative chemo radiation in improving local control, as this is the predominant mode of failure in these patients leading to poor outcomes. This Phase II study design would be used to proceed with the study treatment after meeting pre-specified events in the initial phase, with goal being to determine whether the new treatment paradigm is sufficiently promising to warrant a major controlled clinical evaluation against the standard therapy.

Research Team

Michel Lacroix, M.D.

Principal Investigator

Geisinger Clinic

Eligibility Criteria

This trial is for adults with newly diagnosed, resectable glioblastoma confirmed by pathology. Participants must be fit for surgery, have a Karnofsky Performance Status over 70 (meaning they are able to care for themselves), and have proper organ function including adequate blood counts and liver function. Pregnant women or those who could become pregnant must test negative and agree to use contraception.

Inclusion Criteria

Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3

I am able to care for myself but may not be able to do active work.

My recent blood test shows I have enough white blood cells, platelets, and hemoglobin.

Exclusion Criteria

I am not pregnant and willing to use birth control during the study.

I am currently on IV antibiotics for a bacterial or fungal infection.

Any other major medical illnesses or psychiatric treatments that in the investigator's opinion will prevent administration or completion of protocol therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemoradiation

Participants receive neoadjuvant chemoradiation prior to surgical resection

7 months

Surgical Resection

Participants undergo surgical resection of the tumor following chemoradiation

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Neoadjuvant chemoradiation
• Surgery post Radiation and Temozolomide (benzolamide)
• Temozolomide (benzolamide)

Trial Overview The study is testing the effectiveness of chemoradiation before surgery in patients with glioblastoma. It's a Phase II trial where participants will receive Temozolomide alongside radiation therapy prior to their tumor being surgically removed, comparing this approach against standard treatment protocols.

Participant Groups

Group I: Neoadjuvant chemoradiation and surgical resection Experimental Treatment 3 Interventions

The experimental part of the study would be this selection of resectable patients and sequencing neoadjuvant chemoradiation prior to surgery.

Temozolomide (benzolamide) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Temodar for:

• Glioblastoma multiforme
• Refractory anaplastic astrocytoma

Approved in European Union as Temodal for:

• Glioblastoma multiforme
• Refractory anaplastic astrocytoma

Approved in Canada as Temodal for:

• Glioblastoma multiforme
• Refractory anaplastic astrocytoma

Who Is Running the Clinical Trial?

Geisinger Clinic

Lead Sponsor

Trials

159

Recruited

1,976,000+

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]

In a study of 128 patients with high-grade gliomas, the combination of radiotherapy and temozolomide showed favorable outcomes, with only 9% experiencing grade 3 hematological toxicity and no grade 4 toxicity reported, indicating a manageable safety profile.

Statistical analysis revealed that factors such as age, tumor histology, and the use of temozolomide were linked to improved 2-year overall survival, supporting the efficacy of this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and radiotherapy as first-line treatment of high-grade gliomas. Corsa, P., Parisi, S., Raguso, A., et al.[2022]

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]

In a randomized trial involving 447 patients with recurrent high-grade glioma, temozolomide (TMZ) did not show a clear survival advantage over procarbazine, lomustine, and vincristine (PCV), with a hazard ratio of 0.91, indicating similar effectiveness.

However, within the TMZ treatment groups, the 5-day regimen demonstrated better overall progression-free survival and quality of life compared to the 21-day regimen, suggesting that shorter treatment schedules may be more effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma. Brada, M., Stenning, S., Gabe, R., 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]

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]

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]

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]

Temozolomide (TMZ) is shown to be more cost-effective than the traditional PCV treatment for glioblastoma multiforme (GBM), with costs of €2367 per extra life-month and €32,471 per quality-adjusted life-year (QALY).

The analysis indicates that TMZ has a high probability (over 60%) of being the most cost-effective treatment option at various willingness-to-pay thresholds, especially when considering quality of life improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic evaluation of temozolomide in the treatment of recurrent glioblastoma multiforme. Martikainen, JA., Kivioja, A., Hallinen, T., et al.[2018]

In a phase 2 clinical trial involving 27 patients with brain metastases from breast cancer and non-small cell lung cancer, a new regimen combining whole-brain radiotherapy (WBRT) with a prolonged low-dose temozolomide (TMZ) treatment showed promising antitumor activity, achieving a 7.4% complete response and a 40.7% partial response.

The treatment was well tolerated, with only 2 patients experiencing grade 3 toxicity, and resulted in a median overall survival of 8.8 months and a median progression-free survival of 6 months, indicating its potential as a viable option for treating brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 trial of temozolomide using protracted low-dose and whole-brain radiotherapy for nonsmall cell lung cancer and breast cancer patients with brain metastases. Addeo, R., De Rosa, C., Faiola, V., et al.[2022]

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

Temozolomide and radiotherapy as first-line treatment of high-grade gliomas. [2022]

3. 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]

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

Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma. [2022]

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

[Temozolomide: Temodal]. [2018]

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

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

7. Germany pubmed.ncbi.nlm.nih.gov

Bioequivalence study of 20-mg and 100-mg temozolomide capsules (TOZ309 and Temodal®) in glioma patients in China. [2021]

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

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

9. New Zealand pubmed.ncbi.nlm.nih.gov

Economic evaluation of temozolomide in the treatment of recurrent glioblastoma multiforme. [2018]

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

Phase 2 trial of temozolomide using protracted low-dose and whole-brain radiotherapy for nonsmall cell lung cancer and breast cancer patients with brain metastases. [2022]