WP1066 + Radiation for Glioblastoma

Recruiting at 1 trial location

Overseen By Christina Amidei

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: Anticancer therapy, Antiretrovirals

Disqualifiers: Uncontrolled seizures, Brain hemorrhage, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1066

Duration: 6 weeks

39 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial requires that you stop any active anti-cancer therapy and certain medications that interact with specific enzymes at least 2 weeks before starting the trial. If you are on medications that interact with CYP450 enzymes, you may need to stop them 2 weeks prior, and for some other medications, 7 days prior. Please consult with the trial team to review your current medications.

What data supports the effectiveness of the treatment WP1066 + Radiation for Glioblastoma?

Intraoperative radiotherapy (IORT) has shown promise in targeting tumor cells left after surgery and improving outcomes in glioblastoma treatment, as seen in the INTRAGO study. Additionally, combining stereotactic radiosurgery (SRS) with immunotherapy has demonstrated a survival benefit in animal models of glioma, suggesting potential effectiveness when combined with other treatments like WP1066. ^{1 2 3 4 5}

Is the combination of WP1066 and radiation therapy safe for treating glioblastoma?

The safety of various radiation therapies, including intraoperative radiotherapy and brachytherapy, has been evaluated in clinical trials for brain tumors like glioblastoma. These studies generally report that these therapies are feasible and have a manageable safety profile, although specific safety data for WP1066 combined with radiation therapy is not detailed in the provided research. ^{1 2 6 7 8}

What makes the WP1066 + Radiation treatment unique for glioblastoma?

The WP1066 + Radiation treatment is unique because it combines a novel drug, WP1066, which inhibits STAT3 (a protein involved in cancer cell growth), with various forms of radiation therapy. This combination aims to enhance the effectiveness of radiation by potentially boosting the immune response against glioblastoma, a strategy not commonly used in standard treatments. ^{1 3 9 10 11}

What is the purpose of this trial?

This phase II trial tests how well the combination of WP1066 and radiation therapy works in treating newly diagnosed glioblastoma. Glioblastoma is difficult to treat effectively because the cells within the tumor vary widely and are controlled by factors within and around the tumor, requiring multiple approaches to treat the tumor. The study drug WP1066 targets a specific pathway, known as STAT3, which is responsible for promoting tumor growth and causing the body's immune system to avoid attacking the tumor. Radiation therapy prevents glioblastoma from growing. Giving WP1066 with radiation therapy may prevent glioblastoma from growing and prolong survival.

Research Team

Amy Heimberger

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for adults with newly diagnosed, histologically confirmed glioblastoma multiforme (GBM), IDH wild-type. Participants must have certain blood and organ function levels within normal ranges and be able to undergo MRI with contrast. Women of childbearing potential and men must agree to use contraception during the study.

Inclusion Criteria

I have been newly diagnosed with a specific type of brain tumor called glioblastoma.

I have measurable brain disease confirmed by an MRI within the last 4 weeks.

My doctors believe surgery could help manage my symptoms.

Exclusion Criteria

I have received bevacizumab before.

I am using Optune and cannot safely stop it before starting the trial therapy.

I have received gene therapy before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive WP1066 orally for 6 weeks during routine radiation therapy

6 weeks

Weekly visits for radiation therapy

Extended Treatment

Patients continue to receive WP1066 for twelve 28-day cycles

12 months

Monthly visits for WP1066 administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Regular follow-up visits including MRI and blood sample collection

Treatment Details

Interventions

• Radiation Therapy
• WP1066

Trial Overview The trial examines how well WP1066, a STAT3 inhibitor, works alongside radiation therapy in treating glioblastoma. It aims to target pathways promoting tumor growth and immune evasion. The effectiveness of this combination treatment on tumor control and survival is being studied.

Participant Groups

Group I: Cohort II (WP1066, radiation, surgery) Experimental Treatment 5 Interventions

Patients whose tumor was not fully removed at the time of initial surgery receive WP1066 PO for 6 weeks during routine radiation therapy on study. Patients may then undergo possible surgery or open biopsy if eligible, followed by twelve 28-day cycles of WP1066 PO on study. Patients also undergo MRI and collection of blood samples throughout the trial.

Group II: Cohort I (WP1066, radiation) Experimental Treatment 4 Interventions

Patients whose tumor was completely removed at the time of initial surgery receive WP1066 PO for 6 weeks during routine radiation therapy, and then for twelve 28-day cycles on study. Patients also undergo MRI and collection of blood samples throughout the trial.

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

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Moleculin Biotech, Inc.

Industry Sponsor

Trials

8

Recruited

550+

Findings from Research

Adjuvant locoregional radio-immunotherapy (RIT) was well tolerated in 12 patients with malignant glioma, showing promising results with a median survival of 18.5 months, compared to 9.7 months for historical controls receiving conventional treatments.

RIT allows for targeted delivery of treatment directly to the tumor site, effectively bypassing the blood-brain barrier and minimizing systemic toxicity, which could enhance therapeutic outcomes for glioma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Initial experiences with adjuvant locoregional radioimmunotherapy using 131I-labeled monoclonal antibodies against tenascin (BC-4) for treatment of glioma (WHO III and IV)]. Pöpperl, G., Götz, C., Gildehaus, FJ., et al.[2016]

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]

The combination of anti-GITR monoclonal antibody (mAb) and stereotactic radiosurgery (SRS) significantly improved survival rates in a mouse model of glioblastoma, with a cure rate of 24% compared to 0% for either treatment alone, indicating a strong immune-mediated effect.

The treatment with anti-GITR (1) and SRS led to increased infiltration of CD4+ effector T-cells and enhanced production of immune signaling molecules like IFNγ and IL-2, suggesting that this combination effectively shifts the immune response against the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune-mediated survival advantage in murine intracranial glioma. Patel, MA., Kim, JE., Theodros, D., et al.[2022]

In a study of 101 patients with malignant glioma, only 27% were eligible for adjuvant stereotactic radiosurgery, and these eligible patients had significantly longer median survival times (23.4 months) compared to ineligible patients (8.6 months).

The findings suggest a substantial selection bias in uncontrolled trials of stereotactic radiosurgery, indicating that a phase III randomized study may not be necessary as it is unlikely to show positive results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring bias in uncontrolled brain tumor trials--to randomize or not to randomize? Irish, WD., Macdonald, DR., Cairncross, JG.[2019]

A bibliometric analysis of 5106 articles on radiotherapy for gliomas revealed a significant increase in citations from 356 in 2011 to 21,051 in 2020, indicating growing interest and research impact in this area.

The research trends highlighted a heightened focus on glioblastoma, survival rates, and the role of chemotherapy in conjunction with radiotherapy, suggesting evolving strategies in glioma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Global Research Trends in Radiotherapy for Gliomas: A Systematic Bibliometric Analysis. Zhang, Y., Lim, D., Yao, Y., et al.[2022]

GammaTile® Surgically Targeted Radiation Therapy (STaRT) offers a novel approach to brain tumor treatment by using a bioresorbable tile that delivers radiation while minimizing direct contact with brain tissue, which helps reduce normal brain toxicity.

This therapy has been FDA approved since 2018 for recurrent brain tumors and expanded in 2020 to include newly-diagnosed malignant tumors, with ongoing trials aimed at comparing its efficacy and safety against standard radiation treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically targeted radiation therapy (STaRT) trials for brain neoplasms: A comprehensive review. Odia, Y., Gutierrez, AN., Kotecha, R.[2023]

The study involving 10 patients with CNS tumors demonstrated that GliaSite brachytherapy is a feasible and safe treatment option, with no severe acute or late toxicities observed during follow-up.

Median survival after treatment was 14 months, with acceptable local control rates, suggesting that this method could be a promising approach for managing newly diagnosed and recurrent CNS malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of dose escalation with intracavitary brachytherapy in the treatment of localized CNS malignancies: outcomes and toxicities of a prospective study. Wernicke, AG., Sherr, DL., Schwartz, TH., et al.[2018]

In a study of 73 patients with glioblastoma multiforme, locoregional radioimmunotherapy (LR-RIT) demonstrated a safety profile with 75% of patients achieving disease stabilization and no major hematological toxicity observed.

The combination of LR-RIT with Temozolomide (TMZ) significantly improved overall survival (25 months) and progression-free survival (10 months) compared to LR-RIT alone, indicating that this combined treatment approach is both effective and safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined treatment of glioblastoma patients with locoregional pre-targeted 90Y-biotin radioimmunotherapy and temozolomide. Bartolomei, M., Mazzetta, C., Handkiewicz-Junak, D., et al.[2018]

In a clinical trial involving 32 patients with malignant glioma, neutron brachytherapy using Cf-252 showed a well-tolerated implantation procedure and provided short-term survival benefits for those who completed the planned radiotherapy.

Older patients experienced less tolerance to the radiotherapy, indicating that the overall effectiveness of Cf-252 brachytherapy may depend on a patient's ability to endure the full treatment course.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical study with brain brachytherapy for malignant gliomas. Chin, HW., Maruyama, Y., Young, B., et al.[2013]

Intraoperative radiotherapy (IORT) for Glioblastoma results in lower exposure to organs-at-risk (OARs) compared to pre-operative single-fraction stereotactic radiosurgery (SRS), making it a safer option for patients.

The study analyzed 17 treatment plans and found that while SRS provided excellent target coverage, IORT led to significantly lower doses to critical structures like the optic nerves and retina, suggesting it may be a more effective approach in minimizing side effects during dose escalation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric Comparison of Upfront Boosting With Stereotactic Radiosurgery Versus Intraoperative Radiotherapy for Glioblastoma. Sarria, GR., Smalec, Z., Muedder, T., et al.[2022]

A prospective study involving 35 patients with newly diagnosed glioblastoma showed that stereotactic brachytherapy, combined with surgery and external radiotherapy, significantly improved survival rates, with 1-year and 2-year survival rates of 87% and 57%, respectively.

In comparison, a matched control group of 40 patients treated with standard surgery and external radiotherapy had much lower survival rates of 40% at 1 year and 12.5% at 2 years, highlighting the potential efficacy of brachytherapy in enhancing patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of stereotactic brachytherapy used in the initial management of patients with glioblastoma. Loeffler, JS., Alexander, E., Wen, PY., et al.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Initial experiences with adjuvant locoregional radioimmunotherapy using 131I-labeled monoclonal antibodies against tenascin (BC-4) for treatment of glioma (WHO III and IV)]. [2016]

2. England pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune-mediated survival advantage in murine intracranial glioma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Measuring bias in uncontrolled brain tumor trials--to randomize or not to randomize? [2019]

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

Global Research Trends in Radiotherapy for Gliomas: A Systematic Bibliometric Analysis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Surgically targeted radiation therapy (STaRT) trials for brain neoplasms: A comprehensive review. [2023]

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

The role of dose escalation with intracavitary brachytherapy in the treatment of localized CNS malignancies: outcomes and toxicities of a prospective study. [2018]

8. Italy pubmed.ncbi.nlm.nih.gov

Combined treatment of glioblastoma patients with locoregional pre-targeted 90Y-biotin radioimmunotherapy and temozolomide. [2018]

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

A clinical study with brain brachytherapy for malignant gliomas. [2013]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Dosimetric Comparison of Upfront Boosting With Stereotactic Radiosurgery Versus Intraoperative Radiotherapy for Glioblastoma. [2022]

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

Results of stereotactic brachytherapy used in the initial management of patients with glioblastoma. [2019]