Combination Therapy for Glioblastoma

Overseen By Michael Dominello, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Barbara Ann Karmanos Cancer Institute

Must not be taking: Bevacizumab, Carmustine, others

Disqualifiers: Recurrent glioblastoma, Metastatic GBM, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of a combination treatment for newly diagnosed glioblastoma, an aggressive brain cancer. The treatment includes 3-Dimensional Conformal Radiation Therapy, the chemotherapy drug temozolomide, chloroquine (typically used for malaria), and tumor treating fields therapy, which uses electric fields to target cancer cells. The goal is to understand how these therapies work together to combat glioblastoma. Individuals recently diagnosed with glioblastoma who have recovered from surgery might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking research.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Research shows that each part of this trial has undergone prior safety testing.

For radiation therapy, studies indicate that both 3D-Conformal Radiation Therapy and Intensity-Modulated Radiation Therapy are generally safe for treating glioblastoma. These methods target the cancer area, helping to protect healthy brain tissue. Most people tolerate them well, though some side effects might occur.

Temozolomide, a chemotherapy drug commonly used for brain tumors like glioblastoma, is generally well-tolerated, but some patients may experience side effects such as low blood cell counts. Serious side effects are less common but can occur.

Chloroquine, typically used for malaria, is under study for cancer treatment. Research suggests it can enhance the effectiveness of other treatments and is generally safe, though side effects can vary.

Tumor Treating Fields Therapy uses electric fields to attack cancer cells. Over 25,000 patients have used it, with only minor skin issues reported. It doesn't cause other widespread side effects.

The trial is in its early phase, focusing on safety. This means the treatment hasn't been tested in many people yet. The trial aims to provide more information about any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination therapy for glioblastoma because it integrates several innovative approaches that could potentially enhance treatment effectiveness. Unlike standard treatments, which typically involve either radiation or chemotherapy alone, this regimen combines 3D Conformal Radiation Therapy or Intensity-Modulated Radiation Therapy (IMRT) with temozolomide, chloroquine, and Tumor Treating Fields (TTF). Chloroquine, traditionally an anti-malarial drug, is being used here to help improve the cancer-fighting ability of radiation and chemotherapy by interfering with the tumor's protective mechanisms. Additionally, TTF is a novel technique that uses electric fields to disrupt cancer cell division, offering a non-invasive option with minimal side effects. This multi-pronged strategy aims to target glioblastoma from multiple angles, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

Research has shown that the combination of treatments in this trial may help treat glioblastoma, a type of brain cancer. Participants will receive radiation therapy, such as 3D-Conformal and Intensity-Modulated Radiation Therapy (IMRT), which uses focused high-energy rays to shrink tumors and has effectively managed glioblastoma. Studies have found that Temozolomide, a chemotherapy drug included in this trial, greatly improves survival rates when combined with radiation therapy. Chloroquine, typically a malaria medication, might enhance the effects of radiation and tumor treating fields therapy, which helps slow tumor growth. Tumor treating fields therapy uses electric fields to stop cancer cells from dividing and has improved survival in glioblastoma patients. These findings suggest that combining these treatments, as done in this trial, could effectively manage glioblastoma. ^{3 6 7 8 9}

Who Is on the Research Team?

Michael Dominello, MD

Principal Investigator

Barbara Ann Karmanos Institute

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed glioblastoma who have recovered from surgery without complications. They must not have had previous chemotherapy or radiosensitizers for head and neck cancers (except certain conditions), no severe heart disease, eye disorders, or other major illnesses that could interfere with the treatment. Women of childbearing potential must use effective contraception and have a negative pregnancy test.

Inclusion Criteria

My kidney function, measured by creatinine clearance, is adequate.

I have been diagnosed with a grade IV brain tumor.

I have signed the consent form for this study.

Exclusion Criteria

History of hypersensitivity to temozolomide or excipients

Severe, active, co-morbidity defined as follows: Moderate or severe hepatic impairment (Child-Pugh category B or higher [score of 7 or higher ]); unstable angina and/or congestive heart failure within the last 6 months; transmural myocardial infarction within the last 6 months; evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days prior to enrollment; New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to enrollment; History of stroke, cerebral vascular accident (CVA), or transient ischemic attack within 6 months (except if intra- or post-operative); serious and inadequately controlled cardiac arrhythmia; acute bacterial or fungal infection requiring intravenous antibiotics at the time of enrollment; chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of enrollment; uncontrolled human immunodeficiency virus (HIV) with CD4 count < 200; note, however, that HIV testing is not required for entry into this protocol; Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy; Subjects treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study, except intra-operative therapy to guide resection or experimental imaging without therapeutic intent; Inability to undergo contrast-enhanced MRI scans; Presence of implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, or other implanted electronic devices in the brain; Documented clinically significant arrhythmia or severe ischemic heart disease; Patients with underlying ocular disorders, including but not limited to: maculopathy, macular degeneration, and retinopathy

I have been cancer-free for 5 years, except for certain skin cancers and early-stage cancers.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Participants undergo 30 fractions of 3D CRT or IMRT and receive temozolomide and chloroquine daily for the duration of radiation therapy up to day 49

7 weeks

Daily visits for radiation therapy

Adjuvant Treatment

Beginning 4 weeks after radiation, participants receive temozolomide and chloroquine with TTF therapy for up to 6 cycles, potentially extending to 12 cycles

6-12 months

Monthly visits for each cycle

Follow-up

Participants are monitored monthly for 3 months after completion of study treatment

3 months

Monthly visits

What Are the Treatments Tested in This Trial?

Interventions

• 3-Dimensional Conformal Radiation Therapy
• Chloroquine
• Intensity-Modulated Radiation Therapy (IMRT)
• Temozolomide
• Tumor Treating Fields Therapy (TTF)

Trial Overview The study tests the combination of partial brain radiation therapy, temozolomide (a chemotherapy drug), chloroquine (an antimalarial drug thought to enhance cancer treatments), and tumor treating fields therapy (TTF) which uses electric fields to disrupt cancer cell growth in patients with glioblastoma.

How Is the Trial Designed?

Group I: Treatment (radiation therapy, temozolomide, chloroquine, TTF) Experimental Treatment 5 Interventions

Patients undergo 30 fractions of 3D CRT or Intensity-modulated radiation therapy (IMRT) and receive temozolomide by mouth (PO) and chloroquine PO daily from day 1 for the duration of radiation therapy up to day 49. Treatment continues in the absence of disease progression or unacceptable toxicity. ADJUVANT TREATMENT: Beginning 4 weeks after the last day of radiation therapy, patients receive temozolomide PO QD on days 1-5 and chloroquine PO daily on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients demonstrating continued benefit may continue to receive temozolomide and chloroquine for up to 12 cycles. Patients also undergo TTF therapy over 18 hours or longer per day.

3-Dimensional Conformal Radiation Therapy is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in European Union as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Canada as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Japan as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in China as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Switzerland as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Who Is Running the Clinical Trial?

Barbara Ann Karmanos Cancer Institute

Lead Sponsor

Trials

166

Recruited

9,300+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10705506/

Comparison of the Effectiveness of Radiotherapy with 3D-CRT ... This study investigated the effectiveness of different modern radiotherapy strategies in the treatment of patients with newly diagnosed glioblastoma

2. frontiersin.org frontiersin.org/journals/physics/articles/10.3389/fphy.2025.1632620/full

Three-dimensional conformal therapy vs. intensity ... These findings align with evidence suggesting IMRT outperforms conventional techniques like 3DCRT in glioblastoma management [9, 12, 37, 38, 44]. IMRT enables ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11467484/

Recurrence pattern of glioblastoma treated with intensity ... IMRT and 3D-CRT effectively managed glioblastoma with no significant differences in OS and PFS. The survival benefit with GTR underscored the ...

4. pagepressjournals.org pagepressjournals.org/gc/article/download/14114/13460

comparing the effectiveness of 3D conformal radiation therapy ... This study aimed to evaluate the survival efficacy of different radiotherapy strategies in patients with glioblastoma (GBM). Furthermore, by utilizing various ...

5. redjournal.org redjournal.org/article/S0360-3016(17)31794-7/pdf

Evaluation of Clinical Outcomes in Glioblastoma Multiforme ... Few studies reviewed the data of two clinical scenarios in the treatment of patients diagnosed with glioblastoma multiforme (GBM): intensity-modulated ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2913423/

RTOG 9803 - PMC - PubMed Central This is the first, large prospective multi-institutional study to analyze the acute and long-term toxicity of conformal 3DCRT of more than 60 Gy with concurrent ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301608009280

Phase I Three-Dimensional Conformal Radiation Dose ... The study hypothesized that the use of highly conformal 3D-CRT with smaller treatment margins may permit safe dose escalation without increasing central nervous ...

8. e-roj.org e-roj.org/journal/view.php?doi=10.3857/roj.2024.00381

Recurrence pattern of glioblastoma treated with intensity ... IMRT and 3D-CRT effectively managed glioblastoma with no significant differences in OS and PFS. The survival benefit with GTR underscored the importance of ...

9. cureus.com cureus.com/articles/364616-assessment-and-comparison-of-3d-conformal-radiotherapy-with-volumetric-modulated-arc-therapy-for-preserving-remaining-brain-volume-in-high-grade-gliomas

Assessment and Comparison of 3D Conformal ... Median overall survival (OS) is 14-20 months after optimal multimodality treatment. For the past two decades, the standard technique has been ...