Regorafenib for Glioblastoma

Overseen By David Peereboom, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Case Comprehensive Cancer Center

Must not be taking: Anticoagulants, Herbal remedies

Disqualifiers: Cardiac disease, Hypertension, Hepatitis, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called Regorafenib (also known as Stivarga, BAY 73-4506, or Regonix) to assess its safety and tolerability for people with glioblastoma, a type of brain cancer that has returned or worsened after treatment with bevacizumab. The trial aims to assist patients who have undergone previous treatments but still face challenges with their condition. Suitable participants have glioblastoma, have tried bevacizumab, and have experienced cancer returning or progressing despite treatment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial requires you to stop any current anti-cancer therapy and certain medications like warfarin and herbal remedies such as St. John's wort. If you're on corticosteroids, you must be on a stable or decreasing dose before starting the trial.

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

Research has shown that regorafenib is generally safe, consistent with previous findings. Importantly, these studies reported no deaths related to the drug. However, serious side effects occurred in about 56% of patients. Because these side effects can vary, participants must be monitored closely. The FDA has already approved regorafenib for other uses, indicating a certain level of established safety. However, individual reactions can differ with any treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glioblastoma?

Regorafenib is unique because it targets multiple pathways involved in tumor growth and blood vessel formation, offering a novel approach for treating glioblastoma, especially in cases where the tumor has become resistant to Avastin. Unlike standard treatments, regorafenib inhibits several protein kinases, which can help slow down the progression of this aggressive brain cancer. Researchers are particularly excited about its potential to overcome resistance in glioblastoma, providing hope for improved outcomes in a condition with limited effective treatment options.

What evidence suggests that Regorafenib might be an effective treatment for glioblastoma?

Research has shown that regorafenib, the treatment under study in this trial, may aid in treating glioblastoma, particularly for patients whose cancer has returned after other treatments. Studies have found that regorafenib can extend patient survival compared to lomustine, with patients living an average of 7.4 months instead of 5.6 months. Regorafenib blocks certain proteins that promote tumor growth, potentially slowing or halting cancer progression. Overall, early evidence suggests that regorafenib could be a promising option for those with recurrent glioblastoma. ^{2 3 4 6 7}

Who Is on the Research Team?

David Peereboom, MD

Principal Investigator

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with recurrent glioblastoma who have previously not responded to bevacizumab treatment. They must have certain blood and organ function levels, agree to use contraception if of childbearing potential, and cannot have other concurrent cancers (with some exceptions). Participants need a life expectancy of at least 12 weeks and should not be on any conflicting medications or treatments.

Inclusion Criteria

I am not receiving any cancer treatments other than the study treatment.

It has been over 3 weeks since my last non-nitrosourea chemotherapy.

I have been on a stable or decreasing dose of corticosteroids, not exceeding 4mg/day.

Exclusion Criteria

I am on blood thinners, but not warfarin, and have no history of bleeding disorders.

I have been treated with Regorafenib before.

I haven't had major surgery or significant injury in the last 4 weeks, or minor procedures in the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 160 mg regorafenib 3 weeks on/one week off until progression or toxicity

Up to 3 years

MRI every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Regorafenib

Trial Overview

The study tests the safety and tolerability of Regorafenib, an FDA-approved drug, in patients with glioblastoma that has recurred after prior treatments including chemotherapy and radiotherapy. The trial will involve up to 22 participants who meet strict eligibility criteria.

How Is the Trial Designed?

Group I: Regorafenib Experimental Treatment 1 Intervention

160 mg regorafenib 3 weeks on/ one week off in participants with Avastin refractory Glioblastoma, continued until progression or toxicity. Participants will receive an MRI every 8 weeks.

Regorafenib is already approved in United States, European Union for the following indications:

Approved in United States as Stivarga for:

• Metastatic colorectal cancer
• Gastrointestinal stromal tumors (GIST)
• Hepatocellular carcinoma (HCC)

Approved in European Union as Stivarga for:

• Metastatic colorectal cancer
• Gastrointestinal stromal tumors (GIST)
• Hepatocellular carcinoma (HCC)

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11062143/

Regorafenib and glioblastoma: a literature review of ...

In this study, it has been observed that relapsed GBM patients treated with regorafenib experienced an increase in overall survival (OS) when compared to the ...

2.

esmoopen.com

esmoopen.com/article/S2059-7029(24)00711-7/fulltext

REGOMA-OSS: a large, Italian, multicenter, prospective, ...

Regorafenib showed a significant improvement in overall survival (OS) compared with lomustine [7.4 months versus 5.6 months, hazard ratio (HR) ...

3.

frontiersin.org

frontiersin.org/journals/radiology/articles/10.3389/fradi.2021.790456/full

Regorafenib in Glioblastoma Recurrence: How to Deal ...

Regorafenib is a multi-kinase inhibitor that has recently been introduced into clinical practice to treat recurrent glioblastoma, bringing with it a novel ...

4.

cambridge.org

cambridge.org/core/journals/expert-reviews-in-molecular-medicine/article/regorafenib-and-glioblastoma-a-literature-review-of-preclinical-studies-molecular-mechanisms-and-clinical-effectiveness/2B920C92C713B917F080F41629A0C205

Regorafenib and glioblastoma: a literature review of ...

In this study, it has been observed that relapsed GBM patients treated with regorafenib experienced an increase in overall survival (OS) when ...

5.

nature.com

nature.com/articles/s41598-022-20417-y

Clinical and NGS predictors of response to regorafenib in ...

The regorafenib arm showed a significantly longer overall survival (OS), both in terms of median OS (7.4 vs 5.6 months, respectively; p = 0.0009) ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11718784/

Regorafenib Treatment for Recurrent Glioblastoma Beyond ...

The safety profile was consistent with that of the REGOMA trial, with no drug-related deaths observed. Conclusions: Regorafenib shows good ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S2059702924007117

REGOMA-OSS: a large, Italian, multicenter, prospective, ...

The safety profile of regorafenib was consistent with data in the literature, with grade 3-4 adverse events occurring in 56% of treated patients, most commonly ...