Capecitabine + Bevacizumab for Glioblastoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Case Comprehensive Cancer Center

Must not be taking: Antiretrovirals

Disqualifiers: Uncontrolled illness, HIV, other malignancy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: Variable (until progression)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with recurrent glioblastoma, a type of brain tumor that has returned or continued growing despite previous treatments. The trial aims to determine if a combination of low-dose capecitabine (Xeloda) and bevacizumab (Avastin) can alter the tumor environment and reduce tumor size. Individuals with a confirmed diagnosis of grade 4 glioma who plan to have a tumor removed may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment approach.

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

The trial information does not specify if you need to stop taking your current medications. However, there are specific intervals required from prior treatments, and certain medications like investigational agents and some HIV treatments are not allowed. It's best to discuss your current medications with the trial team to get a clear answer.

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

Research shows that the combination of capecitabine and bevacizumab is generally safe for patients with glioblastoma. In earlier studies, patients who took these drugs did not experience serious treatment-related side effects. Specifically, low doses of capecitabine with bevacizumab proved safe. This combination has been used in various cancer treatments without causing major side effects in these studies. Additionally, bevacizumab has been used for a long time in other types of solid tumors and has been well-tolerated over extended periods. These findings help reassure about the safety of these treatments in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of capecitabine and bevacizumab for glioblastoma because it introduces a new approach to tackling this aggressive brain cancer. Unlike the standard treatments that primarily focus on surgery, radiation, and chemotherapy such as temozolomide, this combo offers a unique mechanism by combining an oral chemotherapy agent, capecitabine, which disrupts cancer cell DNA, with bevacizumab, an IV-administered drug that inhibits blood vessel growth to the tumor. This dual-action strategy aims to not only directly attack cancer cells but also cut off their blood supply, potentially enhancing effectiveness and slowing tumor progression.

What evidence suggests that Capecitabine + Bevacizumab might be an effective treatment for glioblastoma?

Studies have shown that combining capecitabine and bevacizumab may help treat certain cancers. Specifically, research on patients with colorectal cancer found that this combination prevented cancer progression for an average of 10.3 months, with about 30% of patients experiencing tumor shrinkage. Although these results do not specifically apply to glioblastoma, they suggest that this drug combination might help control tumor growth in some cancers. In this trial, participants will receive capecitabine and bevacizumab to determine if these benefits extend to glioblastoma, focusing on immune cells that aid tumor survival. ^{2 3 6 7 8}

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 not been treated with capecitabine or bevacizumab. They must have a stable physical condition, no major bleeding risks, controlled blood pressure, and the ability to swallow tablets. Pregnant women and those with certain infections or recent heart issues are excluded.

Inclusion Criteria

Patients must have specific minimum intervals from prior treatments

Subjects must have the ability to understand and the willingness to sign a written informed consent document

Women of childbearing potential must have a negative pregnancy test within 21 days of study entry and agree to use adequate contraception

Exclusion Criteria

I am allergic to medications similar to capecitabine or bevacizumab.

I haven't had any other cancer besides this one in the last 2 years.

I have a long-term stomach problem that causes severe diarrhea.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low dose capecitabine and bevacizumab in 28-day cycles until progression

Variable (until progression)

Visits on days 1 and 15 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Capecitabine

Trial Overview

The study tests if low dose capecitabine can target MDSCs to potentially reverse immunosuppression in the brain tumor environment of GBM patients, combined with bevacizumab which may help reduce tumors by inhibiting blood vessel growth.

How Is the Trial Designed?

Group I: Treatment: Capecitabine + Bevacizumab Experimental Treatment 2 Interventions

Capecitabine, PO dose to be determined by phase 1 dose escalation, cycle length 28 days. Treated with Bevacizumab, IV, 10 mg/kg days 1, 15 every 28 days, until progression.

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

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/PMC3235996/

Efficacy of Bevacizumab-Capecitabine in Combination for the ...

Efficacy data was similar to other reported studies of capecitabine plus bevacizumab, with median PFS of about 8 months, ORR of 20% and 35% stable disease.

2.

onclive.com

onclive.com/view/capecitabine-bevacizumab-yields-antitumor-activity-and-a-favorable-safety-profile-in-older-mcrc-population

Capecitabine/Bevacizumab Yields Antitumor Activity and a ...

The study showed a median PFS of 10.3 months and an ORR of 30.3% in elderly mCRC patients treated with capecitabine plus bevacizumab. · The ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8649003/

A Long‐Term Extension Study of Bevacizumab in Patients ...

This study assessed the long‐term safety and tolerability of bevacizumab among patients with solid tumors.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00642603?tab=results

Study Results | A Study of Xeloda (Capecitabine) in ...

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

5.

assets.roche.com

assets.roche.com/f/170883/x/0d70f29b60/avastin-pi-jul-2022.pdf

Avastin™

The efficacy results of Avastin in combination with IFL-chemotherapy are displayed in Table. 4 and Figure 1 (Kaplan Meier plot for duration of survival).

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02669173

Capecitabine + Bevacizumab in Patients With Recurrent ...

This study involves participants with recurrent glioblastoma brain tumors (GBM). This means that a participant's brain tumor has either returned after being ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/31600167/

Metronomic capecitabine as an immune modulator ... - PubMed

CONCLUSIONSLow-dose, metronomic capecitabine in combination with bevacizumab was well tolerated in GBM patients and was associated with a ...

8.

consultqd.clevelandclinic.org

consultqd.clevelandclinic.org/low-dose-chemotherapy-reduces-myeloid-derived-suppressor-cells-in-glioblastoma

Low-Dose Chemotherapy Reduces Myeloid-Derived ...

All three doses of capecitabine were reported to be well tolerated in combination with bevacizumab, with no serious adverse events related to ...