Radiation and Temozolomide vs. PCV Chemotherapy for Brain Tumor

Recruiting at 304 trial locations

Overseen By Kurt Jaeckle, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: Retroviral therapy

Disqualifiers: Pregnancy, Nursing, HIV, Active infection, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

305 Participants Needed

Trial Summary

What is the purpose of this trial?

Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving radiation with concomitant and adjuvant temozolomide versus radiation with adjuvant PCV is more effective in treating anaplastic glioma or low grade glioma.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get specific guidance based on your situation.

What data supports the effectiveness of the treatment Radiation and Temozolomide for brain tumors?

Research shows that adding temozolomide to radiotherapy for brain tumors like glioblastoma can improve survival. Patients receiving both treatments lived longer and had better outcomes compared to those who only received radiotherapy. ^{1 2 3 4 5}

Is the combination of radiation and temozolomide safe for treating brain tumors?

Temozolomide, when used with radiation therapy, is generally considered safe and well-tolerated in humans, although it can cause severe myelotoxicity (damage to the bone marrow) in some cases. Studies have shown it has a good safety profile, even in patients with brain metastases from other solid tumors. ^{2 6 7 8 9}

How is the treatment of radiation and temozolomide different from other treatments for brain tumors?

This treatment is unique because it combines radiation therapy with temozolomide, a drug that can cross the blood-brain barrier (a protective shield around the brain) and has shown effectiveness in treating brain tumors. This combination has been shown to improve response rates compared to radiation therapy alone. ^{1 2 7 10 11}

Research Team

Kurt Jaeckle, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for patients with newly diagnosed anaplastic glioma or low grade glioma who have had surgery at least 2 weeks prior and are willing to provide tissue samples. They must not have received previous radiation or chemotherapy, be able to complete tests personally, and agree to use contraception. Excluded are those with severe diseases, recent hepatitis, pregnant/nursing women, history of other cancers within 5 years, heart issues within 6 months, HIV on retroviral therapy.

Inclusion Criteria

My brain tumor is grade II or III with specific genetic changes.

My brain tumor is a mixed glioma with specific genetic features (1p and 19q co-deletion).

My low-grade brain tumor is considered high-risk.

Exclusion Criteria

I am of childbearing age and not willing to use birth control.

I have a serious condition that weakens my immune system, not caused by steroids.

I am HIV positive and currently on retroviral therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo radiation therapy as part of the treatment regimen

5-7 weeks

Daily visits for radiation therapy

Chemotherapy

Patients receive chemotherapy with either temozolomide or PCV regimen

24-42 weeks

Regular visits for chemotherapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 16 years

Every 12 weeks for 1 year, then every 4 months for 2 years, then every 6 months

Treatment Details

Interventions

• CCNU
• Radiotherapy
• Temozolomide

Trial Overview The study compares two treatments: one combines radiation therapy with temozolomide (both during and after radiation), while the other uses radiation followed by PCV chemotherapy (vincristine, CCNU/lomustine, procarbazine). The goal is to determine which treatment is more effective in stopping tumor growth in brain tumors like anaplastic glioma or low grade glioma.

Participant Groups

Group I: Arm B (RT, temozolomide) Experimental Treatment 3 Interventions

Patients undergo RT as in arm I and receive temozolomide PO QD on days 1-5 for 5-7 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant temozolomide PO QD days 1-5. Treatment with adjuvant temozolomide repeats every 4 weeks for 6-12 courses in the absence of disease progression and unacceptable toxicity.

Group II: Arm A (RT, procarbazine, lomustine, vincristine) Experimental Treatment 4 Interventions

Patients undergo 3D-CRT or IMRT on days 1-5 for 5-7 weeks. Patients also receive procarbazine hydrochloride PO on days 8-21, lomustine PO on day 1 and vincristine sulfate IV on days 8 and 29 of courses 3-8. Treatment repeats every 6-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in United States as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Canada as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Japan as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in China as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Switzerland as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

European Organisation for Research and Treatment Center (EORTC)

Collaborator

Trials

1

Recruited

310+

Findings from Research

Combining brain radiotherapy (RT) with temozolomide (TMZ) significantly improves the objective response rate (ORR) in patients with brain metastases, with an odds ratio of 2.27, indicating a better response to treatment compared to RT alone.

However, this combination treatment does not lead to a significant improvement in overall survival (OS) or progression-free survival (PFS), and it is associated with increased adverse effects, such as severe nausea and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis. Zhao, Q., Qin, Q., Sun, J., et al.[2018]

Combining temozolomide with radiotherapy significantly improves the overall response rate (ORR) in patients with brain metastases, particularly in those with non-small cell lung cancer, with a risk ratio of 1.35.

However, this combination treatment does not lead to significant improvements in progression-free survival (PFS) or overall survival (OS) and is associated with a higher incidence of side effects compared to radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Temozolomide and Radiotherapy on Brain Metastatic Tumor: A Systematic Review and Meta-Analysis. Ma, W., Li, N., An, Y., et al.[2018]

In a study of 79 patients with glioblastoma, the combination of radiotherapy and temozolomide resulted in a median overall survival of 18.3 months and 2-year survival rate of 37.1%, which aligns with previous international studies.

The main side effect observed was hematologic toxicity in 8.8% of patients, indicating that while the treatment is effective, monitoring for blood-related side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome of concomitant chemoradiotherapy followed by adjuvant temozolomide therapy for glioblastaomas: single-center experience. Jeon, HJ., Kong, DS., Park, KB., et al.[2018]

In a study of 70 patients with newly diagnosed glioblastoma, combining bevacizumab (BV) with radiation therapy (RT) and temozolomide (TMZ) resulted in improved progression-free survival (PFS) of 13.6 months compared to 7.6 months in a control group, although overall survival (OS) was similar between groups.

The presence of MGMT promoter methylation in tumor tissue was associated with better OS and PFS, suggesting that this biomarker may help identify patients who could benefit more from the treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. Lai, A., Tran, A., Nghiemphu, PL., et al.[2022]

Temozolomide is a chemotherapeutic agent that effectively crosses the blood-brain barrier and has shown a good safety profile in treating brain metastases from solid tumors, with clinical activity observed in heavily pretreated patients.

In a randomized phase II trial, temozolomide combined with radiation therapy resulted in a significantly higher objective response rate (96% vs. 67%) compared to radiation alone, particularly benefiting patients with newly diagnosed brain and lung metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide for treating brain metastases. Abrey, LE., Christodoulou, C.[2019]

In a study of 87 newly diagnosed glioblastoma patients, only 5% experienced severe myelotoxicity during treatment with temozolomide (TMZ) and radiation therapy, indicating that while the risk exists, it is relatively low.

Factors such as female sex, low pretreatment platelet counts, and specific genetic markers were identified as potential predictors of severe myelotoxicity, suggesting that personalized treatment approaches could help mitigate risks in vulnerable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. Lombardi, G., Rumiato, E., Bertorelle, R., et al.[2018]

References

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

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis. [2018]

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

Effects of Temozolomide and Radiotherapy on Brain Metastatic Tumor: A Systematic Review and Meta-Analysis. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical outcome of concomitant chemoradiotherapy followed by adjuvant temozolomide therapy for glioblastaomas: single-center experience. [2018]

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

Effectiveness of temozolomide for primary glioblastoma multiforme in routine clinical practice. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Health-related quality of life in patients with high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. [2023]

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

Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. [2022]

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

Temozolomide for treating brain metastases. [2019]

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

Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. [2018]

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

Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: a phase II randomized trial. [2018]

10. Singapore pubmed.ncbi.nlm.nih.gov

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

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

Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. [2018]