XRD-0394 + Radiation Therapy for Brain Tumor

Overseen By Cancer Trials NYU Langone

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: NYU Langone Health

Must not be taking: CYP3A4 inhibitors, BCRP inhibitors

Disqualifiers: Bone marrow impairment, Cardiac abnormalities, others

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

Compensation: Varies

Number of Visits: Unknown

39 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications. However, if you are receiving anti-glioma therapy, you need to stop it 14 days before the first dose of XRD-0394 and can resume it at least 5 days after completing XRD-0394. Also, you cannot take drugs that strongly affect the CYP3A4 enzyme or BCRP within 14 days before the trial or during participation.

What data supports the effectiveness of the treatment XRD-0394 + Radiation Therapy for Brain Tumor?

Research shows that combining surgery and radiation is effective for treating brain tumors, with improved survival rates when higher doses of radiation are used during surgery. Additionally, combining surgery with radiation therapy is a proven approach for brain tumors, enhancing treatment results. ^{1 2 3 4 5}

Is the combination of XRD-0394 and radiation therapy safe for humans?

Radiation therapy, like Gamma Knife radiosurgery, can have side effects such as adverse radiation effects (ARE), which may require treatment with medications like steroids. Safety measures, such as careful dose planning, can help reduce these effects. ^{6 7 8 9 10}

What makes the treatment XRD-0394 + Radiation Therapy for Brain Tumor unique?

This treatment combines a new drug, XRD-0394, with radiation therapy to target brain tumors. XRD-0394 may enhance the effects of radiation, potentially improving outcomes compared to radiation alone. This approach is novel as it integrates a drug specifically designed to work with radiation, which could offer a more effective treatment option for brain tumors. ^{3 4 11 12 13}

What is the purpose of this trial?

This is an open-label, dose-finding study of XRD-0394 in subjects with newly diagnosed and recurrent high grade gliomas receiving radiation therapy, with and without concurrent temozolomide based on O6-Methylguanine-DNA methyltransferase (MGMT) status for patients with newly diagnosed high grade gliomas.

Research Team

Jonathan Yang, MD, PhD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for adults with high-grade gliomas, a type of brain tumor. Participants must be in stable condition (ECOG ≤2), able to consent, and have adequate liver/kidney function. Women and men must prevent pregnancy. Exclusions include heart issues, swallowing problems, prior similar treatments for new cases, or strong drug interactions.

Inclusion Criteria

I can perform daily activities with minimal assistance.

Willing and able to provide written informed consent

I have been diagnosed with a high-grade brain tumor.

Exclusion Criteria

Subjects with a QTc interval >450 msec at screening

I have a history of swallowing problems or chronic stomach issues.

Subjects who are pregnant or breast-feeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Surgical Dose-Escalation

Patients with newly-diagnosed high grade gliomas receive neoadjuvant radiation therapy with XRD-0394 before surgery

8 days

Daily visits for radiation therapy

Post-Surgery Dose Escalation

MGMT-methylated and unmethylated patients receive XRD-0394 concurrently with radiation therapy after surgical resection

108 days

Twice or three times weekly visits for drug administration

Dose-Escalation (No Surgery)

Patients with recurrent high-grade glioma receive XRD-0394 concurrently with radiation therapy

44 days

Twice or three times weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Radiation Therapy
• Surgical Resection
• XRD-0394

Trial Overview The study tests XRD-0394 combined with radiation therapy on patients with newly diagnosed or recurrent high-grade gliomas. Some may also receive temozolomide depending on their MGMT status. The goal is to find the right dose of XRD-0394 that's effective when given alongside standard therapies.

Participant Groups

Group I: Pre-Surgery Dose-Escalation Experimental Treatment 3 Interventions

Patients with newly-diagnosed high grade gliomas (HGG) receiving neoadjuvant radiation therapy (RT) prior to surgical resection will be enrolled in the Pre-Surgical Dose-Escalation arm, at one of two dose levels: Participants enrolled at Pre-Surgical Dose Level 1 (DL1) will receive 160mg daily XRD-0394 on the days of radiation therapy before surgery. Participants enrolled at Pre-Surgery Dose Level 2 (DL2) will receive 300mg daily XRD-0394 on the days of radiation therapy before surgery. All patients enrolled in the pre-surgical dose escalation portion of the study will receive DL1 in the post-surgical dose-escalation portion of the study, but will not be enrolled in the Post-Surgery Dose Escalation arms for purpose of analysis.

Group II: Cohort C: Dose-Escalation (No Surgery) Experimental Treatment 2 Interventions

Patients with recurrent high-grade glioma (HGG) will be enrolled in Cohort C. Participants enrolled at Dose-Level 1 (DL1) will receive 160 mg XRD-0394 administered twice weekly, concurrently with radiation therapy. Participants enrolled at Dose-Level 2 (DL2) will receive 160 mg XRD-0394 administered three times weekly, concurrently with radiation therapy. Participants enrolled at Dose-Level 2 (DL3) will receive 300 mg XRD-0394 administered three times weekly, concurrently with radiation therapy.

Group III: Cohort B: Post-Surgery Dose Escalation Experimental Treatment 3 Interventions

MGMT-unmethylated patients will be enrolled in Cohort B following surgical resection. Participants enrolled at Post-Surgery Dose-Level 1 (DL1) will receive 160 mg XRD-0394 administered twice weekly, concurrently with radiation therapy. Participants enrolled at Post-Surgery Dose-Level 2 (DL2) will receive 160 mg XRD-0394 administered three times weekly, concurrently with radiation therapy. Participants enrolled at Post-Surgery Dose-Level 2 (DL3) will receive 300 mg XRD-0394 administered three times weekly, concurrently with radiation therapy.

Group IV: Cohort A: Post-Surgery Dose Escalation Experimental Treatment 3 Interventions

MGMT-methylated patients will be enrolled in Cohort A following surgical resection. Participants enrolled at Post-Surgery Dose-Level 1 (DL1) will receive 160 mg XRD-0394 administered twice weekly, concurrently with radiation therapy. Participants enrolled at Post-Surgery Dose-Level 2 (DL2) will receive 160 mg XRD-0394 administered three times weekly, concurrently with radiation therapy. Participants enrolled at Post-Surgery Dose-Level 3 (DL3) will receive 300 mg XRD-0394 administered three times weekly, concurrently with radiation therapy.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Findings from Research

Combining surgery with radiation therapy is currently the most effective treatment for central nervous system tumors, highlighting the importance of a multi-faceted approach to cancer care.

The article emphasizes the role of advanced neuroimaging techniques in enhancing the success of surgical interventions for brain tumors, suggesting that improved imaging can lead to better surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurosurgical management of brain tumors. Tatter, SB.[2012]

Salvage stereotactic radiotherapy (SRT) using CyberKnife for recurrent gliomas showed an acceptable safety profile, with only 11.4% of patients experiencing significant toxicity, specifically radiation-induced brain necrosis.

The treatment resulted in a median overall survival of 9 months and a progression-free survival of 3 months, indicating that SRT can be a viable option for patients with recurrent gliomas after initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Salvage Re-irradiation With Stereotactic Radiotherapy for Recurrent Glioma Using CyberKnife. Adachi, K., Hayashi, K., Kagawa, N., et al.[2019]

Radiation therapy is essential for treating brain tumors, utilizing various techniques to improve patient outcomes.

The review covers both traditional methods and advanced techniques like intensity-modulated radiotherapy and stereotactic radiosurgery, highlighting the evolution of treatment options available for effective tumor management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation techniques in neuro-oncology. Khuntia, D., Tomé, WA., Mehta, MP.[2021]

A new method for delivering interstitial radiation therapy using 192Ir seeds in brain tumors has been developed, which involves CT-guided stereotactic localization and computerized dose planning.

Preliminary results from seven patients show promising outcomes with no serious complications reported, indicating the method's potential safety and efficacy in treating brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of brain tumors with iridium-192 seeds. Kaneko, I., Noguchi, M., Kogure, T., et al.[2019]

References

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

Neurosurgical management of brain tumors. [2012]

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

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

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[Radiotherapy of primary brain tumors]. [2016]

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Low-Energy X-Ray Intraoperative Radiation Therapy (Lex-IORT) for Resected Brain Metastases: A Single-Institution Experience. [2023]

5. Spain pubmed.ncbi.nlm.nih.gov

[Use of radiotherapy in the treatment of brain tumors]. [2007]

6. Ireland pubmed.ncbi.nlm.nih.gov

Clinical and radiographic adverse events after Gamma Knife radiosurgery for brainstem lesions: A dosimetric analysis. [2021]

7. Greece pubmed.ncbi.nlm.nih.gov

Feasibility of Salvage Re-irradiation With Stereotactic Radiotherapy for Recurrent Glioma Using CyberKnife. [2019]

8. India pubmed.ncbi.nlm.nih.gov

Adverse Radiation Effects Following Gamma Knife Radiosurgery. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Low-Dose Gamma Knife Radiosurgery for Vestibular Schwannomas: Tumor Control and Cranial Nerve Function Preservation After 11 Gy. [2020]

10. Greece pubmed.ncbi.nlm.nih.gov

Hypofractionated Gamma Knife Radiosurgery: Institutional Experience on Benign and Malignant Intracranial Tumors. [2022]

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

Radiation techniques in neuro-oncology. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Treatment of brain tumors with iridium-192 seeds. [2019]

13. Italy pubmed.ncbi.nlm.nih.gov

Therapeutic strategy for central nervous system tumors: present status, criticism and potential. [2017]