Radiation and Temozolomide vs. PCV Chemotherapy for Brain Tumor

Not currently recruiting at 310 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatment combinations to determine which is more effective for certain brain tumors, specifically anaplastic glioma and low-grade glioma. One group will receive radiation therapy (radiotherapy) with the chemotherapy drug temozolomide. The other group will receive radiation combined with a mix of chemotherapy drugs: procarbazine, lomustine (CCNU), and vincristine. Suitable candidates for this trial are those diagnosed with these specific brain tumors who have not yet undergone chemotherapy or radiation. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that using temozolomide with radiotherapy is generally safe and can benefit patients with brain tumors. This combination improves the quality of life and survival rates for individuals with malignant gliomas, a type of brain tumor. Temozolomide, a newer drug, has shown promise in treating difficult tumors.

Another treatment option is PCV chemotherapy, which includes procarbazine, lomustine, and vincristine, also used with radiotherapy. While effective, PCV can have different side effects and may be harder to tolerate due to the involvement of multiple chemotherapy drugs.

Both treatment options have been well-studied. Although each has side effects, they are considered safe for treating certain brain tumors. Clinical trial participants will be closely monitored for any side effects to manage them effectively. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for brain tumors because they offer different approaches compared to traditional options. Arm A combines radiotherapy with a chemotherapy regimen of procarbazine, lomustine, and vincristine, which allows for a multi-drug attack on cancer cells, potentially enhancing effectiveness. Arm B pairs radiotherapy with temozolomide, which is known for its ability to penetrate the brain more effectively and target tumor DNA, potentially leading to better outcomes with fewer side effects. These innovative combinations aim to improve survival rates and reduce toxicity compared to standard chemotherapy alone.

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

Research has shown that combining radiation therapy with temozolomide, which participants in this trial may receive, can extend the lives of people with brain tumors, such as gliomas. One study found that 70% of patients were alive after 10 years when treated with both temozolomide and radiation, compared to 47% who received only radiation. Temozolomide works by stopping tumor cells from growing. Another treatment option in this trial is radiation therapy combined with PCV chemotherapy, which includes procarbazine, lomustine, and vincristine. Studies have found that PCV can help patients live longer without disease progression. Both treatments show promise, but their effectiveness can depend on the type of tumor. ^{4 6 7 8 9}

Who Is on the Research Team?

Kurt Jaeckle, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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

Various blood counts and laboratory values must meet specified criteria

Willingness to provide blood samples for correlative research

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

Citations

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Study Details | NCT00003375 | Observation or Radiation ... Patients may receive treatment if tumor recurs. Arm II (high-risk patients): Patients receive daily external beam radiotherapy 5 days a week for 6 weeks.

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