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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a reduced dose of radiation, combined with the standard drug temozolomide, can slow the progression of glioblastoma, an aggressive brain tumor. Participants will receive a new form of radiotherapy called pulsed reduced dose radiotherapy (pRDR), which uses lower doses in pulses, alongside chemotherapy. This approach may suit those recently diagnosed with glioblastoma who have undergone surgery and are scheduled for radiation and chemotherapy. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that pulsed reduced dose radiotherapy (pRDR) is generally well-tolerated. A large review found low rates of serious side effects, specifically grade 3 toxicity, in patients with recurring aggressive brain tumors, suggesting it is relatively safe for those receiving this treatment.

The trial also uses temozolomide (TMZ), a chemotherapy drug. Studies have shown that temozolomide is safe for older adults and can extend their lives when used after radiation therapy. It has been effective in treating glioblastoma, a type of brain cancer.

Overall, both treatments have demonstrated promising safety in past research, making them reasonable options for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Pulsed reduced dose-rate radiotherapy (pRDR) is unique because it offers a new approach to treating glioblastoma by combining reduced-dose radiotherapy with temozolomide, a chemotherapy drug. Unlike traditional radiotherapy, which can be intense and taxing on the body, pRDR uses lower doses delivered in pulses, potentially reducing side effects while still fighting cancer cells effectively. Researchers are excited about this treatment because it aims to maintain the effectiveness of standard treatments while improving the quality of life for patients by minimizing harmful side effects.

What evidence suggests that pulsed reduced dose radiotherapy might be an effective treatment for glioblastoma?

Research has shown that pulsed reduced dose radiotherapy (pRDR) can help patients with glioblastoma live longer. Studies have found that pRDR, especially when combined with bevacizumab (a cancer-fighting drug), can significantly extend the time patients live without disease progression and increase overall survival time. In one study, patients lived a median of about 12.6 months after receiving pRDR treatment.

In this trial, participants will receive pRDR in combination with Temozolomide, another well-known treatment for glioblastoma. Research indicates that Temozolomide improves patient outcomes when combined with radiation therapy. Specifically, patients who received both Temozolomide and radiation lived longer than those who had only radiation. This combination is considered a standard treatment to help glioblastoma patients live longer. ^{1 5 6 7 8}

Who Is on the Research Team?

Michael W. Straza

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8655709/

Pulsed Reduced Dose Rate Radiotherapy in Conjunction With ... This retrospective analysis suggests that treatment with pRDR in addition to bevacizumab could significantly prolong PFS and overall survival compared with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11154132/

Pulsed reduced-dose rate re-irradiation for patients with ... 69% of patients showed malignant transformation to grade 3 (38%) or grade 4 (31%) glioma. Overall survival following PRDR was 12.6 months (95% CI: 8.3–17.0 ...

3. practicalradonc.org practicalradonc.org/article/S1879-8500(17)30109-1/abstract

Intensity modulated radiation therapy with pulsed reduced ... The median overall survival and 6-month overall survival after PRDR treatment was 8.7 months and 71%, respectively. Fifty percent of patients had ≥4 ...

4. redjournal.org redjournal.org/article/S0360-3016(22)01551-6/abstract

Re-Irradiation Using Pulsed Reduced Dose Rate Radiation ... 69% of patients showed malignant transformation to grade 3 (38%) or grade 4 (31%) glioma. Overall survival following PRDR was 12.6 months (95% ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04747145

Study Details | NCT04747145 | Analyzing Pulsed Reduced ... This is a single-arm, single-center phase 2 study designed to assess the efficacy of pulsed reduced dose-rate radiotherapy in the initial treatment of ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0360301623053804

Pulsed Reduced Dose Rate Re-Irradiation for Recurrent ... In this large, retrospective cohort, PRDR re-irradiation for recurrent grade 4 gliomas was well tolerated with low rates of grade 3 toxicity.

7. cco.amegroups.org cco.amegroups.org/article/view/139535/html

Pulsed reduced dose rate radiotherapy: a narrative review - Atak Conclusions: PRDR radiotherapy shows promising efficacy and safety across various malignancies, especially in the re-irradiation setting. It is particularly ...

8. academic.oup.com academic.oup.com/noa/article/6/1/vdae073/7668086

Pulsed reduced-dose rate re-irradiation for patients with ... 69% of patients showed malignant transformation to grade 3 (38%) or grade 4 (31%) glioma. Overall survival following PRDR was 12.6 months (95% ...