38 Participants Needed

Veliparib + Radiation + Temozolomide for Brain Cancer

Recruiting at 172 trial locations
Age: < 65
Sex: Any
Trial Phase: Phase 2
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

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

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not be currently receiving other anti-cancer agents.

What data supports the effectiveness of the treatment Veliparib + Radiation + Temozolomide for brain cancer?

Research shows that combining temozolomide (a chemotherapy drug) with radiotherapy can improve survival in patients with brain tumors like glioblastoma compared to radiotherapy alone. This suggests that adding temozolomide to radiation treatments may enhance effectiveness.12345

What safety data exists for the combination of Veliparib, Radiation, and Temozolomide in treating brain cancer?

The combination of radiation therapy and temozolomide has been studied for brain metastases and high-grade gliomas, showing some common side effects like neutropenia (low white blood cell count), anemia (low red blood cell count), vomiting, fatigue, and dizziness. Serious blood-related side effects were not observed, but skin reactions have been reported in some cases. Overall, the treatment was considered active and improved quality of life in some patients.56789

What makes the Veliparib + Radiation + Temozolomide treatment unique for brain cancer?

This treatment combines Veliparib, a drug that may enhance the effects of radiation, with Temozolomide, a chemotherapy drug that can cross the blood-brain barrier and has shown effectiveness in treating brain tumors. The combination aims to improve the effectiveness of radiation therapy by making cancer cells more sensitive to it, potentially leading to better outcomes for patients with brain cancer.1011121314

What is the purpose of this trial?

This phase II trial studies how well veliparib, radiation therapy, and temozolomide work in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations. Poly adenosine diphosphate (ADP) ribose polymerases (PARPs) are proteins that help repair DNA mutations. PARP inhibitors, such as veliparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib, radiation therapy, and temozolomide may work better in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations compared to radiation therapy and temozolomide alone.

Research Team

MA

Matthias A Karajannis

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for patients with newly diagnosed malignant glioma without certain mutations (H3 K27M or BRAFV600). Eligible participants are between 3-25 years old, have not received prior tumor-directed therapy, and can start treatment within 31 days after surgery. They must have proper organ function and controlled seizures if present.

Inclusion Criteria

My kidney function, measured by creatinine clearance or GFR, is normal or above.
My bilirubin levels are within the normal range for my age.
I am between 3 and 21 years old.
See 11 more

Exclusion Criteria

I have been diagnosed with gliomatosis cerebri type 1 or 2.
I am currently pregnant.
I am sexually active and capable of having children.
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiotherapy

Patients receive veliparib orally twice daily and undergo 30 daily fractions of radiation therapy 5 days per week for 6-7 weeks

6-7 weeks
30 visits (in-person)

Maintenance Chemotherapy

Patients receive veliparib orally twice daily and temozolomide orally once daily on days 1-5, repeating every 28 days for up to 10 cycles

Up to 10 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 10 years
Every 3 months for year 1, every 4 months for year 2, every 6 months for year 3, then once yearly for years 4-10

Treatment Details

Interventions

  • Radiation Therapy
  • Temozolomide
  • Veliparib
Trial Overview The study tests the effectiveness of veliparib combined with radiation therapy and temozolomide in treating malignant glioma. Veliparib is a PARP inhibitor that may prevent tumor cells from repairing DNA damage, potentially enhancing the effects of chemotherapy and radiation.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (radiation therapy, veliparib, temozolomide)Experimental Treatment3 Interventions
CHEMORADIOTHERAPY PHASE: Patients receive veliparib PO BID and undergo 30 daily fractions of radiation therapy 5 days per week for 6-7 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE CHEMOTHERAPY: Beginning 4 weeks after chemoradiotherapy phase, patients receive veliparib PO BID and temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.

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

🇪🇺
Approved in European Union as Radiation Therapy for:
  • Cancer treatment
  • Palliative care
  • Oropharyngeal cancer
  • Breast cancer
  • Prostate cancer
  • Lung cancer
  • Brain tumors
🇺🇸
Approved in United States as Radiation Therapy for:
  • Cancer treatment
  • Palliative care
  • Oropharyngeal cancer
  • Breast cancer
  • Prostate cancer
  • Lung cancer
  • Brain tumors
🇨🇦
Approved in Canada as Radiation Therapy for:
  • Cancer treatment
  • Palliative care
  • Oropharyngeal cancer
  • Breast cancer
  • Prostate cancer
  • Lung cancer
  • Brain tumors
🇯🇵
Approved in Japan as Radiation Therapy for:
  • Cancer treatment
  • Palliative care
  • Oropharyngeal cancer
  • Breast cancer
  • Prostate cancer
  • Lung cancer
  • Brain tumors
🇨🇳
Approved in China as Radiation Therapy for:
  • Cancer treatment
  • Palliative care
  • Oropharyngeal cancer
  • Breast cancer
  • Prostate cancer
  • Lung cancer
  • Brain tumors
🇨🇭
Approved in Switzerland as Radiation Therapy for:
  • Cancer treatment
  • Palliative care
  • Oropharyngeal cancer
  • Breast cancer
  • Prostate cancer
  • Lung cancer
  • Brain tumors

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

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.
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]
In a randomized trial involving 144 patients with anaplastic astrocytoma (AA) and glioblastoma (GBM), neoadjuvant temozolomide (NeoTMZ) did not show a survival advantage for the overall population or for GBM patients compared to radiotherapy alone.
However, patients with AA who received NeoTMZ had a significantly longer median survival of 95.1 months compared to 35.2 months for those receiving only radiotherapy, indicating a potential benefit of NeoTMZ specifically for AA.
Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial.Malmström, A., Poulsen, HS., Grønberg, BH., et al.[2018]
In a study of 1157 glioblastoma multiforme patients, the addition of temozolomide (TMZ) to radiotherapy (RT) significantly improved median overall survival from 9.0 months with RT alone to 16.2 months with RT + TMZ (P < .001).
The two-year survival rate increased from 4% with RT alone to 25% with the combination of RT and TMZ, confirming the efficacy of TMZ in enhancing survival outcomes in GBM patients.
A population-based study on the effect of temozolomide in the treatment of glioblastoma multiforme.Rønning, PA., Helseth, E., Meling, TR., et al.[2022]

References

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis. [2018]
Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial. [2018]
A population-based study on the effect of temozolomide in the treatment of glioblastoma multiforme. [2022]
[Radiotherapy of adult glial tumors: new developments and perspectives]. [2008]
Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study. [2018]
Intensity-modulated radiation therapy combined with concomitant temozolomide for brain metastases from lung adenocarcinoma. [2020]
Feasibility of preirradiation temozolomide in cases of high-grade gliomas: Our experience and review of literature. [2023]
Future directions for temozolomide therapy. [2019]
Two cases of cutaneous drug eruption associated with temozolomide therapy for glioblastoma. [2018]
Radiosensitization of Glioma Cells by Temozolomide (TMZ): A Colony Formation Assay. [2022]
In Vitro Radiosensitizing Effects of Temozolomide on U87MG Cell Lines of Human Glioblastoma Multiforme. [2020]
12.United Statespubmed.ncbi.nlm.nih.gov
Temozolomide for treating brain metastases. [2019]
Efficacy of synchronous stereotactic radiotherapy with temozolomide combined with whole brain radiotherapy in treating brain metastases originating from non-small cell lung cancer. [2021]
14.United Statespubmed.ncbi.nlm.nih.gov
Effects of Temozolomide and Radiotherapy on Brain Metastatic Tumor: A Systematic Review and Meta-Analysis. [2018]
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