Intraoperative Radiotherapy for Glioblastoma

(INTRAGO-II Trial)

Not currently recruiting at 23 trial locations

Overseen By Daniel Buergy, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Universitätsmedizin Mannheim

Must not be taking: Anti-angiogenics, Chemotherapy

Disqualifiers: Multicentric disease, Previous cranial radiation, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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 adding intraoperative radiotherapy (IORT), a type of radiation administered during surgery, can enhance treatment for newly diagnosed glioblastoma multiforme (GBM), a severe brain cancer. The trial compares two groups: one receiving standard surgery plus IORT and the other receiving only standard surgery, followed by standard chemotherapy and radiation. Ideal participants are adults with a specific type of brain tumor that can be fully removed through surgery and who have not had previous brain radiation or certain cancer treatments. The goal is to determine if this approach can delay the cancer's return, improving progression-free survival. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have had chemotherapy or certain cancer treatments in the past five years, you may not be eligible to participate.

Is there any evidence suggesting that intraoperative radiotherapy is likely to be safe for humans?

Research has shown that intraoperative radiotherapy (IORT) is generally safe for patients. In a study with 436 patients, only 17% experienced complications, indicating that most did not face serious issues. Another study found that using low-dose X-rays for IORT did not lead to severe problems like brain damage or wound issues. Additionally, research on IORT at a dose of 30 Gy demonstrated very low rates of radiation damage to brain tissue, at just 2.9%.

Overall, evidence suggests that IORT is well-tolerated and does not significantly harm patients. This treatment has been used safely in other cases, supporting its safety for glioblastoma patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about intraoperative radiotherapy for glioblastoma because it offers a novel approach by delivering radiation directly to the brain tumor site during surgery. This method targets the cancerous cells more precisely and might reduce the amount of healthy tissue exposed to radiation. Unlike the standard approach, which involves separate sessions of external beam radiotherapy (EBRT) after surgery, this technique integrates radiation into the surgical procedure, potentially enhancing the effectiveness of treatment and reducing overall treatment time. Additionally, this approach could improve patient outcomes by providing a more immediate and focused attack on the tumor, which is crucial for aggressive cancers like glioblastoma.

What evidence suggests that intraoperative radiotherapy is effective for glioblastoma?

Research has shown that using intraoperative radiotherapy (IORT) during surgery might benefit patients with glioblastoma. In this trial, participants in the experimental arm will receive standard surgery plus IORT. Studies have found that IORT can better control cancer in the area where the tumor was removed, potentially preventing its recurrence in the same location. Some studies also suggest that IORT can increase survival chances, with about 25% of patients living for three years. Additionally, when combined with standard treatments, IORT has demonstrated similar survival rates to current methods, indicating it could be an effective option. ^{1 3 5 6 7}

Who Is on the Research Team?

Frank A. Giordano, MD

Principal Investigator

Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Germany

Kevin Petrecca, MD, PhD

Principal Investigator

Department of Neurosurgery, Montréal Neurological, Institute and Hospital, Montréal, Canada

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with newly diagnosed glioblastoma who are fit enough for surgery (KPS ≥ 60%) and have the tumor in a specific brain region. They must have good organ function, no prior anti-cancer treatments like bevacizumab or cranial radiation, not be pregnant or breastfeeding, and agree to use contraception.

Inclusion Criteria

I understand the nature and personal implications of participating in this clinical trial.

My brain tumor can be completely removed by surgery.

My blood, liver, and kidney functions meet the required levels.

Exclusion Criteria

I do not have any health conditions that doctors say will shorten my life to under 5 years.

I do not have fluid leaking from a brain ventricle defect or risk of high radiation dose to vital organs.

I have not had chemotherapy for cancer in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Intraoperative Radiotherapy

Participants undergo standard surgery with intraoperative radiotherapy (20-30 Gy) for the experimental arm

1 week

Radiochemotherapy

Participants receive radiochemotherapy (EBRT: 60 Gy, 75 mg/m2/d temozolomide) followed by adjuvant chemotherapy

6 weeks

Adjuvant Chemotherapy

Participants receive adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days)

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including regular neurological examinations and serial MRI scans

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Intraoperative radiotherapy

Trial Overview The INTRAGO II trial is checking if adding intraoperative radiotherapy (IORT) to standard treatment improves survival without cancer growth in glioblastoma patients. It's a phase III study where participants are randomly assigned to receive either the new approach or just the standard care.

How Is the Trial Designed?

Group I: Experimental Arm (A) Experimental Treatment 4 Interventions

Standard surgery plus intraoperative radiotherapy (20-30 Gy) followed by radiochemotherapy (EBRT: 60 Gy, 75 mg/m2/d temozolomide) and adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days).

Group II: Control Arm (B) Active Control 3 Interventions

Standard surgery followed by radiochemotherapy (EBRT: 60 Gy, 75 mg/m2/d temozolomide) and adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days).

Who Is Running the Clinical Trial?

Universitätsmedizin Mannheim

Lead Sponsor

Trials

106

Recruited

32,800+

Carl Zeiss Meditec AG

Industry Sponsor

Trials

43

Recruited

7,800+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

Published Research Related to This Trial

The INTRAGO study is evaluating the safety and tolerability of intraoperative radiotherapy (IORT) combined with standard treatment for newly diagnosed glioblastoma multiforme (GBM) in patients aged 50 and older, aiming to improve outcomes by targeting residual tumor cells after surgery.

This phase I/II trial uses low-energy x-rays delivered by spherical applicators to optimize irradiation of the resection cavity, with safety assessed through a dose-escalation design focusing on potential complications like wound healing deficits and cerebral bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

INTRAGO: intraoperative radiotherapy in glioblastoma multiforme—a phase I/II dose escalation study. Giordano, FA., Brehmer, S., Abo-Madyan, Y., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38221545/

Efficacy and Safety of Intraoperative Radiotherapy for High- ... Outcomes of interest included complications, IORT failure, survival rates at 12 and 24 months, and mortality. Results: Sixteen studies ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0967586825004977

Intraoperative radiation therapy for glioblastoma and brain ... showed that the addition of IORT resulted in improved local control and comparable overall survival rates with the Stupp protocol.

3. thegreenjournal.com thegreenjournal.com/article/S0167-8140(19)33112-3/fulltext

Intraoperative radiotherapy for glioblastoma Apparently, intraoperative radiotherapy for glioblastoma increases the overall survival rate (~25% at 3 years). •. Local failure was first ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10462513/

Outcome assessment of intraoperative radiotherapy for ... For the IORT cohort, the median OS was 17.5 (0.5-not reached) months and the 1 year-survival rate 61.3% (Fig. 1d). 70 patients from the ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0967586821004422

Intraoperative radiotherapy for glioblastoma: A systematic ... IORT resulted in improved local control and comparable overall survival rates with the Stupp protocol. The overall effect of IORT on GBM treatment is still ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1878875023000669

The Efficacy and Safety of Intraoperative Radiotherapy in ... IORT with low-energy radiography at a dose of 30–40 Gy is generally safe and effective for patients with recurrent glioma.

7. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1548276/full

Efficacy and safety of low-dose X-rays based intraoperative ... No severe radiation-related adverse events, such as cerebral radiation necrosis or wound-related complications, were recorded. Kaplan-Meier ...