Reduced-Dose Radiotherapy + Temozolomide for Glioblastoma

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must be taking: TMZ chemotherapy

Must not be taking: Cytotoxic therapy

Disqualifiers: Prior malignancy, Recurrent gliomas, 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

Compensation: Varies

Number of Visits: Unknown

38 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 it does exclude those who have received other antitumor therapies before enrolling. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Reduced-Dose Radiotherapy + Temozolomide for Glioblastoma?

Research shows that combining pulsed low-dose radiation therapy with temozolomide can be effective for treating glioblastoma, a type of brain cancer, in animal models. Additionally, using pulsed radiation therapy has been found to control tumors effectively while protecting normal tissue better than standard radiation in early studies. ^{1 2 3 4 5}

Is reduced-dose radiotherapy with temozolomide safe for humans?

Studies have shown that combining reduced-dose radiotherapy with temozolomide is generally safe for treating glioblastoma, even in elderly patients and those with recurrent tumors. However, reirradiation can increase the risk of side effects, especially if previous radiation limits are exceeded. ^{1 2 3 4 6}

How is the treatment of reduced-dose radiotherapy with temozolomide for glioblastoma different from other treatments?

This treatment is unique because it uses a pulsed reduced-dose radiotherapy (pRDR), which means the radiation is given in smaller, more frequent doses, combined with temozolomide, a chemotherapy drug. This approach aims to improve effectiveness against glioblastoma, a type of brain cancer, by potentially enhancing the cancer cells' sensitivity to radiation. ^{2 4 7 8 9}

What is the purpose of this trial?

The primary protocol objective is to assess the impact of substituting pulsed reduced dose radiotherapy (pRDR) for standard radiation therapy in the upfront treatment of glioblastoma (GBM) on disease progression.

Research Team

Michael W. Straza

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

Adults diagnosed with new glioblastoma who've had surgery, if needed, and are set for standard chemo-radiotherapy. They should have a life expectancy of over three months, stable health without severe illnesses or prior invasive cancers (except certain skin cancers), and agree to contraception if applicable. Patients can't join if they have recurrent brain tumors, other cancer sites, recent heart issues, connective tissue diseases at high risk for radiation toxicity, kidney failure requiring dialysis, or pregnancy.

Inclusion Criteria

Agree to practice effective barrier contraception during the entire study treatment period from the time of signing the informed consent through four months after the last study intervention (female and male condoms should not be used together), OR

Are surgically sterile, OR

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

Exclusion Criteria

Severe, active comorbidity, defined as follows:

I am on dialysis or have been advised to start dialysis.

I had a severe heart attack in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Maximally safe resection of glioblastoma

1 week

Chemoradiation

Participants receive pulsed reduced dose-rate radiotherapy combined with chemotherapy

6 weeks

Adjuvant Chemotherapy

Participants receive adjuvant chemotherapy

6-12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• pulsed reduced dose radiotherapy (pRDR)
• Temozolomide

Trial Overview The trial is testing pulsed reduced dose radiotherapy (pRDR) as an alternative to standard radiation therapy in combination with Temozolomide chemotherapy for the initial treatment of glioblastoma. The goal is to see how this approach affects disease progression compared to the current standard treatment.

Participant Groups

Group I: Pulsed reduced dose-rate radiotherapy Experimental Treatment 3 Interventions

Chemoradiation, adjuvant chemotherapy.

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Findings from Research

Pulsed low-dose radiation therapy (PLRT) combined with temozolomide (TMZ) significantly delayed tumor growth in a murine model of radioresistant glioblastoma multiforme (GBM), showing superior efficacy compared to standard radiation therapy with TMZ.

PLRT+TMZ resulted in less damage to normal brain tissue and increased vascularization, suggesting it may be a safer and more effective treatment option for GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed versus conventional radiation therapy in combination with temozolomide in a murine orthotopic model of glioblastoma multiforme. Lee, DY., Chunta, JL., Park, SS., et al.[2022]

In a prospective study of 20 patients with newly diagnosed glioblastoma, pulsed radiation therapy (PRT) combined with temozolomide showed promising effectiveness, with a median overall survival of 20.9 months, which is significantly longer than the 14 months observed in a matched cohort receiving standard radiotherapy.

PRT treatment maintained neurocognitive function and quality of life over the 21-month follow-up period, indicating that this therapy is not only effective but also safe for patients' cognitive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed radiation therapy for the treatment of newly diagnosed glioblastoma. Almahariq, MF., Quinn, TJ., Arden, JD., et al.[2021]

In a phase I clinical trial involving nine patients with glioblastoma, simultaneous integrated-boost intensity-modulated radiotherapy (SIB-IMRT) combined with temozolomide was found to be feasible and well tolerated up to a maximum dose of 80Gy.

No dose-limiting toxicities were observed at the highest dose level, indicating that this treatment combination may be safe for patients with malignant glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose escalation study using simultaneous integrated-boost IMRT with temozolomide in patients with unifocal glioblastoma. Truc, G., Bernier, V., Mirjolet, C., et al.[2018]

Temozolomide (TMZ) was found to effectively radiosensitize two out of three human glioblastoma multiforme (GBM) cell lines when combined with single-dose gamma-irradiation, indicating its potential to enhance the effectiveness of radiation therapy.

In a study involving three genetically characterized GBM cell lines, TMZ demonstrated an additive effect with fractionated irradiation, particularly showing a significant reduction in surviving cells in the AMC 3046 cell line, suggesting that TMZ can improve treatment outcomes for certain GBM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential radiosensitizing potential of temozolomide in MGMT promoter methylated glioblastoma multiforme cell lines. van Nifterik, KA., van den Berg, J., Stalpers, LJ., et al.[2018]

References

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

Intensity modulated radiation therapy with pulsed reduced dose rate as a reirradiation strategy for recurrent central nervous system tumors: An institutional series and literature review. [2018]

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

Pulsed versus conventional radiation therapy in combination with temozolomide in a murine orthotopic model of glioblastoma multiforme. [2022]

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

Pulsed reduced dose-rate radiotherapy for previously irradiated tumors in the brain and spine. [2022]

4. Cyprus pubmed.ncbi.nlm.nih.gov

Concomitant temozolomide and radiotherapy versus radiotherapy alone for treatment of newly diagnosed glioblastoma multiforme. [2018]

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

Pulsed radiation therapy for the treatment of newly diagnosed glioblastoma. [2021]

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

Standard (60 Gy) or short-course (40 Gy) irradiation plus concomitant and adjuvant temozolomide for elderly patients with glioblastoma: a propensity-matched analysis. [2022]

7. France pubmed.ncbi.nlm.nih.gov

A phase I dose escalation study using simultaneous integrated-boost IMRT with temozolomide in patients with unifocal glioblastoma. [2018]

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

Efficacy and toxicity of postoperative temozolomide radiochemotherapy in malignant glioma. [2018]

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

Differential radiosensitizing potential of temozolomide in MGMT promoter methylated glioblastoma multiforme cell lines. [2018]