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

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of whole brain radiation, standard chemotherapy (temozolomide), and an additional drug (plerixafor) in patients with glioblastoma. The treatment aims to kill tumor cells and prevent them from returning. Plerixafor has shown promising results in combination with radiation therapy for glioblastoma, including an impressive increase in local tumor control.

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.

What data supports the effectiveness of the drug combination of WBRT, Temozolomide, and 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 and melanoma, suggesting potential benefits for brain cancer treatment. Temozolomide has also shown activity in treating various types of brain tumors, including gliomas. ^{1 2 3 4 5}

Is the combination of whole-brain radiotherapy and temozolomide safe for humans?

Studies have shown that the combination of whole-brain radiotherapy (WBRT) and temozolomide (TMZ) is generally safe for treating brain metastases in patients with non-small-cell lung cancer and melanoma, although specific side effects were not detailed in the provided research. ^{1 2 6 7 8}

What makes the drug combination of WBRT, Temozolomide, and Plerixafor unique for treating brain cancer?

This treatment is unique because it combines whole-brain radiotherapy (WBRT) with Temozolomide, a drug that can cross the blood-brain barrier, potentially enhancing the effectiveness of radiation therapy. The addition of Plerixafor, which is not commonly used in standard treatments for brain metastases, may offer a novel approach to improving outcomes. ^{1 4 7 8 9}

Research Team

Lawrence Recht, MD

Principal Investigator

Stanford Cancer Institute Palo Alto

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

References

1. Singapore 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. [2022]

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

Phase II trial of temozolomide in patients with progressive low-grade glioma. [2022]

3. Singapore pubmed.ncbi.nlm.nih.gov

Effectiveness of temozolomide combined with whole brain radiotherapy for non-small cell lung cancer brain metastases. [2019]

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

Brain metastases from melanoma: is there a role for concurrent temozolomide in addition to whole brain radiation therapy? [2021]

5. Austria pubmed.ncbi.nlm.nih.gov

Temozolomide added to whole brain radiotherapy in patients with multiple brain metastases of non-small-cell lung cancer: a multicentric Austrian phase II study. [2021]

6. China pubmed.ncbi.nlm.nih.gov

[Whole brain radiation therapy plus temozolomide in the treatment of brain metastases from non small cell lung cancer: a meta-analysis]. [2018]

7. Spain pubmed.ncbi.nlm.nih.gov

[Temozolomide in patients with melanoma brain metastases treated with whole brain irradiation]. [2019]

8. United States 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. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Whole-brain irradiation with concomitant daily fixed-dose temozolomide for brain metastases treatment: a randomised phase II trial. [2022]