WBRT + Temozolomide + Plerixafor for Brain Cancer

Overseen By Sophie Bertrand

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Lawrence D Recht

Must not be taking: Avastin, Investigational agents

Disqualifiers: Recent myocardial infarct, Pregnancy, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treat glioblastoma, an aggressive brain tumor. It combines whole brain radiation therapy with the standard chemotherapy drug temozolomide and a new drug, plerixafor (Mozobil), which might help prevent tumor recurrence. The aim is to determine if this combination works better than existing treatments. Individuals who have undergone surgery for glioblastoma and have not received other treatments like Avastin might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

The trial information does not specify if you need to stop taking your current medications. However, it does mention that you cannot have prior or concurrent treatment with Avastin (bevacizumab) or prior exposure to plerixafor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that whole-brain radiotherapy (WBRT) combined with temozolomide (TMZ) is generally safe for treating brain tumors. Patients typically tolerate this combination well, and side effects can be managed. Common side effects include fatigue and nausea, which are typical for radiation and chemotherapy.

Early research on plerixafor suggests it may reduce blood flow in the brain area treated with radiation. This finding is intriguing, but further studies are needed to fully understand its safety. Overall, current evidence indicates this treatment plan is safe for patients. However, as with any medical treatment, it is important to be aware of possible side effects and discuss them with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard care for brain cancer, which typically includes treatments like surgery, radiation, and chemotherapy with drugs such as temozolomide, this innovative approach combines Whole-Brain Radiotherapy (WBRT) and temozolomide with plerixafor. Plerixafor is exciting because it targets the CXCR4 receptor, potentially enhancing the effectiveness of the treatment by mobilizing cancer-fighting cells. This combination aims to improve the therapeutic outcome by attacking the cancer more comprehensively. Researchers are particularly interested in whether this approach can better control brain cancer growth and delay disease progression compared to current treatments.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

This trial will evaluate the combination of whole-brain radiotherapy (WBRT), temozolomide, and plerixafor for treating certain brain cancers, such as glioblastoma. Studies have shown that WBRT combined with temozolomide kills cancer cells and shrinks tumors more effectively than radiation alone. Participants in this trial will receive this combination. Additionally, plerixafor, which may help prevent glioblastoma from returning after radiation treatment, will be administered. An early study suggested that plerixafor could reduce blood flow to the tumor, potentially preventing its growth. This combination treatment aims to improve outcomes for patients with this aggressive brain tumor. ^{3 4 5 6 7}

Who Is on the Research Team?

Lawrence Recht, MD

Principal Investigator

Stanford Cancer Institute Palo Alto

Are You a Good Fit for This Trial?

This trial is for patients with high-grade gliomas, including glioblastoma. They must have had surgery but no other cancer treatments and should be in good enough health to understand the study and give consent. Key requirements include normal liver function tests, adequate kidney function, a negative pregnancy test for women of childbearing age, and an agreement to use effective contraception.

Inclusion Criteria

Patient agrees to use an effective method of contraception (hormonal or two barrier methods) while on study and for at least 3 months following the plerixafor infusion.

Creatinine (Cr) clearance should be > 50 mL/min (at time of screening).

I am a woman who can have children and my pregnancy test is negative.

Exclusion Criteria

I have not had a heart attack or active chest pain in the last 3 months.

I have been treated with plerixafor before.

Pregnant or patients who are breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Resection

Patients undergo maximal safe surgical resection

1 week

Radiation Therapy

Patients undergo radiation therapy for 42 days, initiating whole brain radiation therapy at day 21

6 weeks

Chemotherapy

Patients receive temozolomide daily on days 1-42

6 weeks

Plerixafor Infusion

Patients receive plerixafor by continuous infusion on days 1-28

4 weeks

Maintenance Chemotherapy

Patients receive temozolomide monthly for 6-12 courses

6-12 months

Follow-up

Participants are monitored for adverse events for 30 days after the last dose of Plerixafor and then every 12 weeks for 5 years for survival follow-up

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Plerixafor
• Radiation Therapy
• Temozolomide
• Whole-Brain Radiotherapy (WBRT)

Trial Overview The study is testing if adding Plerixafor to standard treatment (Temozolomide chemo-radiotherapy) along with Whole Brain Radiation Therapy improves outcomes in glioblastoma patients. It's a phase II trial aiming to see how well these combined therapies work at killing tumor cells or stopping their growth.

How Is the Trial Designed?

Group I: Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy Experimental Treatment 4 Interventions

After completion maximal safe surgical resection, patients undergo radiation therapy for 42 days, initiating whole brain radiation therapy at day 21 (dose 16 of radiation therapy) and receive temozolomide daily on days 1 to 42. Beginning 7 days before the completion of whole brain radiation therapy, patients receive plerixafor by continuous infusion on days to 1 to 28. Beginning 1 week after completion of plerixafor infusion and 35 days after completion of whole brain radiation therapy, patients receive temozolomide monthly for 6 to 12 courses in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Temodal for:

• Newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and subsequently as monotherapy treatment
• Children from the age of three years, adolescents and adults with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy

Approved in United States as Temodar for:

• Newly diagnosed glioblastoma concomitantly with radiotherapy and subsequently as monotherapy treatment
• Newly diagnosed or refractory anaplastic astrocytoma

Who Is Running the Clinical Trial?

Lawrence D Recht

Lead Sponsor

Trials

1

Recruited

20+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Published Research Related to This Trial

This meta-analysis aims to evaluate the effectiveness and safety of combining temozolomide (TMZ) with whole brain radiotherapy (WBRT) in patients with brain metastases from non-small cell lung cancer (NSCLC), focusing on outcomes like overall survival and quality of life.

The study will systematically review randomized controlled trials to determine if the addition of TMZ improves clinical outcomes compared to WBRT alone, potentially offering new insights into treatment strategies for advanced NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide plus whole brain radiotherapy for the treatment of non-small-cell lung cancer patients with brain metastases: A protocol of an updated systematic review and meta-analysis. Duan, H., Zheng, SY., Zhou, T., et al.[2022]

Whole-brain radiotherapy (WBRT) combined with temozolomide (TMZ) significantly improves the objective response rate in patients with brain metastases from non-small-cell lung cancer (NSCLC), with a relative risk of 1.43 based on a meta-analysis of 25 clinical trials.

However, this combination treatment also increases the risk of severe hematological (grade III-IV) and gastrointestinal toxicities compared to WBRT alone, indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response and safety of whole-brain radiotherapy plus temozolomide for patients with brain metastases of non-small-cell lung cancer: A meta-analysis. Han, J., Qiu, M., Su, L., et al.[2022]

In a study of 26 patients with brain metastases from malignant melanoma, those treated with whole brain irradiation (WBRT) plus temozolomide (TMZ) had a median survival of 6 months, compared to just 1 month for those receiving WBRT alone.

The addition of TMZ to WBRT significantly improved long-term survival outcomes, indicating that this combination therapy may be more effective for patients with melanoma brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Temozolomide in patients with melanoma brain metastases treated with whole brain irradiation]. Conill, C., Fernández-Ibiza, J., Malvehy, J., et al.[2019]

In a phase II trial involving 46 patients with progressive low-grade glioma, Temozolomide (Temodar) demonstrated a 61% objective response rate, with 24% achieving complete response and 37% achieving partial response.

The treatment showed promising safety, with limited toxicity observed; however, one patient experienced severe complications, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of temozolomide in patients with progressive low-grade glioma. Quinn, JA., Reardon, DA., Friedman, AH., et al.[2022]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-02159

Whole Brain Radiation Therapy with Standard ... Giving whole brain radiation therapy with standard temozolomide chemo-radiotherapy and plerixafor may work better in treating patients with glioblastoma.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2075

A phase II study of plerixafor combined with whole brain ... An early phase trial demonstrated that Plerixafor administration decreased cerebral blood volume (CBV) within the irradiated field of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5911624/

Meta‐analysis of whole‐brain radiotherapy plus ... The aim of this meta‐analysis was to compare the efficiency of whole‐brain radiotherapy (WBRT) plus temozolomide (TMZ) with WBRT for the treatment of brain ...

4. withpower.com withpower.com/trial/phase-3-gliosarcoma-11-2018-ef71d

WBRT + Temozolomide + Plerixafor for Brain Cancer Research shows that combining whole-brain radiotherapy (WBRT) with temozolomide (TMZ) is effective for treating brain metastases in non-small-cell lung cancer ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03746080

Study Details | NCT03746080 | Whole Brain Radiation ... Giving whole brain radiation therapy with standard temozolomide chemo-radiotherapy and plerixafor may work better in treating patients with glioblastoma.

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/results/NCT03746080

Study Results | NCT03746080 | Whole Brain Radiation ... After completion maximal safe surgical resection, patients undergo radiation therapy for 42 days, initiating whole brain radiation therapy at day 21 (dose 16 of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8636221/

Response and safety of whole‐brain radiotherapy plus ... The aim of the present work was to investigate the response and safety of whole‐brain radiotherapy (WBRT) plus temozolomide (TMZ) for patients with brain ...