Intraoperative Radiotherapy for Glioblastoma

(INTRAGO-II Trial)

Recruiting at 21 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

314 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

INTRAGO II resembles a multicentric, prospective, randomized, 2-arm, open-label clinical phase III trial which tests if the median progression-free survival (PFS) of patients with newly diagnosed glioblastoma multiforme (GBM) can be improved by the addition of intraoperative radiotherapy (IORT) to standard radiochemotherapy.

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 intraoperative radiotherapy safe for treating glioblastoma and other brain conditions?

Intraoperative radiotherapy (IORT) has been studied for safety in treating glioblastoma and brain metastases. In a study with brain metastases, 11% of patients experienced perioperative adverse events, but there was no significant difference in complications compared to those who did not receive IORT. Another study on gliomas reported some complications like radionecrosis (tissue damage from radiation), convulsions, abscess, and brain edema (swelling), indicating that while IORT is generally safe, there are potential risks. ^{1 2 3 4 5}

How is intraoperative radiotherapy different from other treatments for glioblastoma?

Intraoperative radiotherapy (IORT) for glioblastoma is unique because it delivers radiation directly to the tumor site during surgery, targeting the area where recurrences are most likely to occur. This approach aims to eliminate remaining cancer cells immediately after tumor removal, potentially improving local control and bridging the gap between surgery and further treatments like chemotherapy and external radiation. ^{2 5 6 7 8}

What data supports the effectiveness of the treatment intraoperative radiotherapy for glioblastoma?

Intraoperative radiotherapy (IORT) for glioblastoma shows promise by directly targeting the area where the tumor was removed, which is where most recurrences happen. Studies have shown that patients receiving IORT had a higher 2-year survival rate compared to those who only received conventional radiation after surgery. ^{2 5 6 8 9}

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. Scotland pubmed.ncbi.nlm.nih.gov

Intraoperative radiotherapy for glioblastoma: A systematic review of techniques and outcomes. [2021]

2. Japan pubmed.ncbi.nlm.nih.gov

[Surgical treatment and radiation therapy for glioblastoma multiforme, with special reference to intraoperative radiotherapy]. [2006]

3. Ireland pubmed.ncbi.nlm.nih.gov

Intraoperative radiotherapy for glioblastoma: an international pooled analysis. [2020]

4. Austria pubmed.ncbi.nlm.nih.gov

[Malignant gliomas--radiotherapy]. [2018]

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

INTRAGO: intraoperative radiotherapy in glioblastoma multiforme—a phase I/II dose escalation study. [2022]

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

Evaluation of Dosimetry Formalisms in Intraoperative Radiation Therapy of Glioblastoma. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Benchmarking Safety Indicators of Surgical Treatment of Brain Metastases Combined with Intraoperative Radiotherapy: Results of Prospective Observational Study with Comparative Matched-Pair Analysis. [2022]

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

Intraoperative radiotherapy for gliomas. [2019]

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

Intraoperative radiotherapy in childhood malignant astrocytoma. [2018]