Chemoradiotherapy vs Biomarker-Guided Therapy for Glioblastoma

Recruiting at1 trial location

Age: 65+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: AHS Cancer Control Alberta

Must not be taking: Temozolomide

Disqualifiers: Recurrent gliomas, Prior malignancy, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing two treatments for elderly patients with brain cancer who are not in good health. One treatment uses a drug called Temozolomide, and the other uses a shorter course of radiation therapy. The goal is to find out if these treatments are as effective as the usual treatment but with fewer side effects.

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 trial coordinators or your doctor to get specific guidance based on your situation.

What data supports the effectiveness of this treatment for glioblastoma?

Research shows that combining temozolomide (a chemotherapy drug) with radiotherapy improves survival in patients with glioblastoma compared to radiotherapy alone. Studies have found that this combination is now the standard treatment, leading to longer survival times for patients. ^{1 2 3 4 5}

Is the treatment with Temozolomide and radiotherapy generally safe for humans?

Temozolomide, used in combination with radiotherapy, is generally well tolerated and considered safe, with common side effects like fatigue, nausea, and vomiting. However, it can cause serious blood-related issues and rare liver damage, and some people may experience skin reactions or allergies. ^{4 6 7 8 9}

How is the chemoradiotherapy treatment for glioblastoma different from other treatments?

This treatment combines radiotherapy with temozolomide (TMZ), a drug that makes cancer cells more sensitive to radiation, potentially improving survival rates compared to radiotherapy alone. Temozolomide is taken orally and works by causing mutations in cancer cells, leading to their death. ^{3 4 5 8 10}

Research Team

Eligibility Criteria

This trial is for elderly (age ≥ 65) GBM patients with a performance status KPS of 60-70. They must have newly-diagnosed, histologically proven glioblastoma and known MGMT promoter methylation status. Participants need stable organ function and agree to use effective birth control. Exclusions include prior invasive malignancies within 3 years, recent heart issues, active hepatitis B, or severe co-morbidities.

Inclusion Criteria

AST < 120 U/L (ie < 3 times ULN)

Platelets ≥ 100 x 109/L

My steroid dose has been stable or decreasing for the last 2 weeks.

Exclusion Criteria

I have been cancer-free for over 3 years, except for non-melanoma skin cancer.

You have a serious health condition that is currently causing problems or complications.

I have been hospitalized for heart issues recently.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard chemoradiotherapy or biomarker-guided therapy based on MGMT promoter methylation status

21 days for initial treatment, followed by up to 6 cycles of adjuvant TMZ

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, then every 6 months for years 3-5

Treatment Details

Interventions

• Radiotherapy (Radiation)
• Temozolomide (Alkylating agents)

Trial Overview The study compares standard chemoradiotherapy (40 Gy radiation with concurrent temozolomide) against biomarker-guided therapy—either temozolomide alone for those with methylated MGMT promoters or just radiotherapy for non-methylated cases—to see which is better for survival without increasing toxicity.

Participant Groups

Group I: Biomarker based treatment Experimental Treatment 1 Intervention

MGMT (+) Temozolomide monotherapy: Patients will receive Temozolomide (TMZ) at a dose of 75 mg/m2 daily for 21 consecutive days. This will be followed by six cycles of TMZ according to the standard 5-day schedule (days 1-5) every 28 days. The dose will be 150 mg/m2 for the first cycle and increased to 200 mg/m2 beginning with the second cycle, so long as there are no hematologic adverse events. Dose will be determined using body surface area (BSA) calculation. MGMT methylation (-) RT monotherapy: Participants will receive radiation treatment with 40Gy / 15 fractions over a period of 21 days (3 weeks).

Group II: Standard Arm: TMZ with concurrent RT (combined modality arm) Active Control 1 Intervention

Patients will receive a total of 21 days of Temozolomide (TMZ), with 15 days of TMZ administered daily with concurrent RT. TMZ will be delivered at a dose of 75 mg/m2, given daily with RT for 15 days, one hour before each session of RT. After a 4-week break, patients will receive six cycles of adjuvant TMZ according to the standard 5-day schedule (days 1-5) every 28 days, up to 6 cycles as tolerated by the patient. The dose will be 150 mg/m2 for the first cycle and increased to 200 mg/m2 beginning with the second cycle, so long as there are no hematologic adverse events, intractable nausea or fatigue.

Radiotherapy is already approved in Canada, Japan, China, Switzerland for the following indications:

Approved in Canada as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Japan as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in China as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Switzerland as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Dr. Peter Jamieson

AHS Cancer Control Alberta

Chief Medical Officer since 2024

MD from the University of Alberta

Andre Tremblay

AHS Cancer Control Alberta

Chief Executive Officer

BA in Political Science from the University of Victoria, MA in Political Science from the University of British Columbia

Findings from Research

In a study of 1157 glioblastoma multiforme patients, the addition of temozolomide (TMZ) to radiotherapy (RT) significantly improved median overall survival from 9.0 months with RT alone to 16.2 months with RT + TMZ (P < .001).

The two-year survival rate increased from 4% with RT alone to 25% with the combination of RT and TMZ, confirming the efficacy of TMZ in enhancing survival outcomes in GBM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A population-based study on the effect of temozolomide in the treatment of glioblastoma multiforme. Rønning, PA., Helseth, E., Meling, TR., et al.[2022]

In a study of 67 patients with newly diagnosed glioblastoma multiforme, the combination of temozolomide, thalidomide, and radiation therapy resulted in a median survival of 73 weeks, indicating a favorable outcome compared to those not receiving adjuvant chemotherapy.

The treatment was generally well tolerated, but the specific benefit of adding thalidomide to temozolomide remains uncertain, as the survival outcomes were similar to those seen with other chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of temozolomide and thalidomide with radiation therapy for newly diagnosed glioblastoma multiforme. Chang, SM., Lamborn, KR., Malec, M., et al.[2018]

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 study of 130 patients with newly diagnosed glioblastoma multiforme (GBM), the combination of temozolomide (TMZ) with radiotherapy (RT) significantly improved median overall survival to 13.4 months compared to 7.7 months with RT alone.

The combination treatment also resulted in a longer median time to progression (10.8 months vs. 5.2 months) and a higher one-year progression-free survival rate (36.6% vs. 7.7%), indicating that TMZ enhances the effectiveness of RT in treating GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme. Athanassiou, H., Synodinou, M., Maragoudakis, E., et al.[2018]

In a study of 432 glioblastoma patients, those receiving daily temozolomide (TMZ) during radiotherapy (7 days a week) had a median survival of 15.7 months, significantly longer than those receiving TMZ only on radiotherapy days (12.6 months) or no TMZ (9.1 months).

The analysis indicated that continuous TMZ administration not only improved survival rates but also showed a significant influence on hazard rates, confirming that while even a reduced TMZ schedule can extend survival, daily administration is more effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide during radiotherapy of glioblastoma multiforme : Daily administration improves survival. Nachbichler, SB., Schupp, G., Ballhausen, H., et al.[2018]

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 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]

Temozolomide (tmz), a common chemotherapy drug for glioblastoma, can cause cutaneous drug eruptions, which are rare side effects that have not been widely reported.

In two cases studied, one patient showed clinical signs of an allergy to tmz without positive tests, while the second case confirmed the allergy through a positive lymphocyte activation test, highlighting the need for awareness of potential dermatologic reactions during tmz treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two cases of cutaneous drug eruption associated with temozolomide therapy for glioblastoma. Deluche, E., Leobon, S., Touraine, F., et al.[2018]

Temozolomide (TMZ) enhances the effectiveness of radiation therapy in treating glioblastoma cells, leading to a significant reduction in colony formation when combined with irradiation, compared to either treatment alone.

While irradiation was more toxic to glioma cells than TMZ, the combination of both treatments increased the sensitivity of glioma cells to radiation, suggesting a potential strategy for improving glioblastoma treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitization of Glioma Cells by Temozolomide (TMZ): A Colony Formation Assay. Babaloui, S., Najafi, M., Mozdarani, H., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

A population-based study on the effect of temozolomide in the treatment of glioblastoma multiforme. [2022]

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

Phase II study of temozolomide and thalidomide with radiation therapy for newly diagnosed glioblastoma multiforme. [2018]

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

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

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

Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Temozolomide during radiotherapy of glioblastoma multiforme : Daily administration improves survival. [2018]

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

Future directions for temozolomide therapy. [2019]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Two cases of cutaneous drug eruption associated with temozolomide therapy for glioblastoma. [2018]

10. Iran pubmed.ncbi.nlm.nih.gov

Radiosensitization of Glioma Cells by Temozolomide (TMZ): A Colony Formation Assay. [2022]