Radiation + Temozolomide for Glioblastoma

Age: 65+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Louisville

Must be taking: Temozolomide

Must not be taking: Antiretrovirals

Disqualifiers: Infection, Heart failure, Angina, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of combining hypofractionated radiotherapy (a type of radiation therapy) with the chemotherapy drug temozolomide to treat glioblastoma, a type of brain cancer. The goal is to evaluate the treatment's effectiveness for individuals aged 70 or older, particularly those without prior treatment for this condition. Participants must have a confirmed diagnosis of glioblastoma or gliosarcoma and be able to manage daily activities independently. The study aims to improve treatment outcomes and understand how the combination therapy affects disease progression. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in glioblastoma treatment.

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 cannot be on other study agents or HIV antiretroviral therapy. 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 a combination of a shorter, more intense form of radiation therapy and the chemotherapy drug temozolomide is generally well-tolerated for treating glioblastoma, a type of brain cancer. Studies indicate that this treatment is as safe as traditional, longer radiation methods.

One study found that using this shorter radiation schedule with temozolomide provided similar results and did not increase serious side effects. Another study confirmed that this approach is practical and manageable, especially for patients in poorer health.

These findings suggest that while side effects can occur, they are usually not severe and are similar to those from standard treatments. This offers some reassurance about the safety of the treatment tested in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for glioblastoma, which typically involves longer courses of radiotherapy, the treatment combining hypofractionated radiotherapy with temozolomide offers a unique approach by shortening the duration of radiation exposure. This method condenses the radiotherapy into a more intense, yet shorter period, potentially reducing the overall treatment time and improving patient convenience. Additionally, temozolomide, an oral chemotherapy, is used both simultaneously with the radiotherapy and then as a follow-up treatment, which might enhance its effectiveness against tumor cells. Researchers are excited about this treatment because it could offer a more efficient and possibly more effective option for patients, while also aiming to maintain or even improve current survival outcomes.

What evidence suggests that this treatment might be an effective treatment for glioblastoma?

Research has shown that combining hypofractionated radiotherapy with temozolomide may be promising for treating glioblastoma, particularly in older adults. Hypofractionated radiotherapy involves fewer treatments with higher doses, offering effectiveness and convenience for patients with a poor prognosis or those living far from treatment centers. Temozolomide, a chemotherapy drug, has significantly improved survival rates when used with radiation therapy, increasing average survival time compared to radiation alone. Specifically, one study found that the 10-year survival rate improved to 70% with the addition of temozolomide to radiation therapy, compared to 47% with radiation alone. These findings suggest that this combined treatment, which all trial participants will receive, could lead to better outcomes for glioblastoma patients. ^{3 4 6 7 8}

Who Is on the Research Team?

Shiao Woo, MD

Principal Investigator

James Graham Brown Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients over 70 with newly diagnosed glioblastoma who haven't had prior treatments. They must have a life expectancy of more than 6 months, good organ and marrow function, and be able to consent. Excluded are those with other cancers (unless low risk or certain types within the past 5 years), severe illnesses, or HIV on antiretrovirals.

Inclusion Criteria

Patients must have normal organ and marrow function: Leukocytes > 3,000/microliter, Absolute neutrophil count > 1,500/microliter, Platelets > 100,000/microliter, Total bilirubin within normal institutional limits, aspartate aminotransferase test(SGOT)/alanine aminotransferase test(SGPT) < 2.5 X institutional upper limit of normal, Creatinine within normal institutional limits or creatinine clearance > 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal, Ability to understand and the willingness to sign a written informed consent document

Participants must have life expectancy greater than 6 months

I am over 70 years old.

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide

Participants may not be receiving any other study agents

I have not had chemotherapy wafers placed during surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive hypofractionated radiotherapy with concurrent temozolomide

2 weeks

Daily visits for radiation therapy

Adjuvant Treatment

Participants receive up to 6 cycles of adjuvant temozolomide treatment

6 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Every 3 months for the first year, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Hypofractionated radiotherapy
• Temozolomide

Trial Overview The study tests a combination of short-term radiation therapy (over two weeks) and Temozolomide chemotherapy during and after radiation in older adults. The goal is to see how well they tolerate this treatment regimen and its effectiveness against their brain cancer.

How Is the Trial Designed?

Group I: Hypofractionated radiotherapy and temozolomide Experimental Treatment 2 Interventions

All subjects will receive treatment as is a single arm study. Two weeks of combined hypofractionated radiotherapy with concurrent temozolomide followed by up to 6 cycles of adjuvant temozolomide treatment.

Hypofractionated radiotherapy is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Hypofractionated radiotherapy for:

• Esophageal adenocarcinoma
• Gastroesophageal junction adenocarcinoma

Approved in United States as Hypofractionated radiotherapy for:

• Esophageal adenocarcinoma
• Gastroesophageal junction adenocarcinoma

Approved in Japan as Hypofractionated radiotherapy for:

• Esophageal squamous cell carcinoma
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

James Graham Brown Cancer Center

Collaborator

Trials

44

Recruited

9,200+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9892549/

Clinical Outcomes of Moderately Hypofractionated ... Hypofractionated radiotherapy (HypoRT) has recently been implemented in patients with glioblastoma (GBM) receiving concurrent temozolomide.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425001009

Comparative Outcomes of Standard Radiation Therapy ... Shorter hypofractionated RT regimens reduce treatment duration, benefiting patients with poor prognoses or those living far from treatment centers, because long ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10778244/

Treatment Outcomes after Dose-Escalated Moderately ... Treatment Outcomes after Dose-Escalated Moderately Hypofractionated Radiotherapy for Frail Patients with High-Grade Glioma. Nalee Kim. Nalee ...

4. ar.iiarjournals.org ar.iiarjournals.org/content/43/6/2725

Identification of Patients With Glioblastoma Who May ... In a randomized trial of elderly patients with glioblastoma, hypofractionated RT with 40 Gy in 15 daily fractions of 2.66 Gy over three weeks was noninferior to ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/0284186X.2023.2238884

The impact of short-course hypofractionated radiotherapy ... In this cohort of 2416 GBM patients, the utilisation of short-course HFRT significantly increased from ca. 10% in 2011 to 33% in recent years.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9648463/

Moderately hypofractionated versus conventionally ... HF-RT may offer equivalent outcomes and reduce treatment burden compared to CF-RT in young, fit GBM patients.

7. eymj.org eymj.org/pdf/10.3349/ymj.2022.0352

Clinical Outcomes of Moderately Hypofractionated ... Our study demonstrated that HypoRT for newly diagnosed. GBM patients receiving concurrent temozolomide shows com- parable oncologic outcomes and ...

8. clinicalkey.com clinicalkey.com/playContent/1-s2.0-S1507136720301176

Hypofractionated radiation therapy with temozolomide ... Conclusion: Our results showed that HFRT with concurrent TMZ is a feasible therapeutic approach in patients with GBM, especially those with poor prognostic ...