ADI-PEG 20 + TMZ + RT for Brain Cancer
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores a new combination of treatments for young patients with newly diagnosed high-grade glioma, a type of brain cancer. It combines the experimental drug ADI-PEG 20 with Temozolomide, a chemotherapy drug, and radiation therapy to assess potential improvements in treatment outcomes. The trial includes different groups to evaluate the treatment's effects on specific glioma types, such as histone wild-type and H3K27 altered diffuse midline gliomas. Patients who have undergone surgery for a high-grade glioma but have not yet received other treatments may be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it does mention that participants must not have received any prior therapy except surgery before enrolling. If you are on medications, especially for seizures, you may need to discuss potential interactions with the study drug with the trial team.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
In earlier studies, ADI-PEG 20 showed promise for treating brain tumors. Research suggests it increases tumor sensitivity to radiation therapy, aiding in shrinkage. The combination of ADI-PEG 20 with radiation and temozolomide (TMZ) proved safe. Some participants developed antibodies against ADI-PEG 20, but this did not cause major issues.
Temozolomide is a standard treatment for aggressive brain tumors and is generally safe. Some studies report blood-related side effects in 5 to 10% of patients, but it is mostly well-tolerated over long periods.
Both ADI-PEG 20 and TMZ have been studied together, demonstrating effective results without serious safety concerns. This suggests the treatment is generally well-tolerated, according to current research.12345Why are researchers excited about this trial's treatments?
Researchers are excited about ADI-PEG 20 for brain cancer because it offers a unique approach by depleting arginine, an amino acid that some tumors rely on to grow. Most existing treatments, like surgery, radiation, and chemotherapies such as temozolomide, focus on directly killing cancer cells or inhibiting their DNA replication. However, ADI-PEG 20 targets the tumor's nutritional needs, potentially adding a new tool to the cancer-fighting arsenal. Additionally, the combination of ADI-PEG 20 with temozolomide and radiotherapy might enhance the overall effectiveness by attacking the cancer from multiple angles. This novel mechanism of action and the potential to improve treatment outcomes make this treatment an exciting prospect for researchers.
What evidence suggests that this trial's treatments could be effective for high grade glioma?
Research has shown that ADI-PEG 20 can help treat certain brain tumors, particularly when the tumor lacks a protein called ASS1, which some tumors need to grow. In this trial, participants in different cohorts will receive ADI-PEG 20 combined with Temozolomide (TMZ) and radiation therapy. Specifically, ADI-PEG 20, when combined with radiation therapy, has extended the time patients remain disease-free. Temozolomide (TMZ) improves survival rates when used with radiation, especially for severe brain tumors known as high-grade gliomas. Together, ADI-PEG 20 and TMZ offer a promising approach to fighting these aggressive brain cancers.46789
Who Is on the Research Team?
Sabine Mueller, MD, PhD
Principal Investigator
University of California, San Francisco
Tom Davidson, MD
Principal Investigator
Children's Hospital Los Angeles
Are You a Good Fit for This Trial?
This trial is for children, adolescents, and young adults with a specific type of brain cancer called high-grade glioma (HGG). They must have had surgery but no other treatments. Ages accepted vary by cohort: generally 3-18 years old, but up to 25 for one group.Inclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Dose Escalation
Participants receive ADI-PEG 20 in combination with radiotherapy and daily TMZ to determine the recommended phase 2 dose (RP2D)
Maintenance Therapy
Participants continue with maintenance therapy consisting of ADI-PEG 20 and TMZ for up to 10 cycles
Extended Maintenance
Participants may continue receiving monotherapy treatment as extended maintenance for up to 10 additional cycles
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- ADI-PEG 20
- Standard of Care Radiation Therapy (RT)
- Temozolomide
Trial Overview
The study tests ADI-PEG 20 combined with Temozolomide (TMZ) and radiation therapy in patients with newly diagnosed HGG. It's an open label trial where doses are adjusted within each patient over time.
How Is the Trial Designed?
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Treatment groups
Experimental Treatment
Participants will be treated at the recommended phase 2 dose (RP2D) of ADI-PEG 20 determined in Phase 1. Participants who complete the combined treatment and maintenance phase may continue receiving monotherapy treatment as extended maintenance for up to 10 additional cycles, provided there is no unacceptable toxicity, disease progression, or withdrawal of consent. ADI-PEG 20 treatment may continue for up to 104 weeks. After completing the 30-day toxicity evaluation period, participants will enter follow-up. Follow-up procedures will be documented under the PNOC COMP protocol, except for protocol-defined follow-up procedures. Participants will be followed under the PNOC COMP protocol until death or withdrawal from the study.
Participants will be treated at the recommended phase 2 dose (RP2D) of ADI-PEG 20 determined in Phase 1. Participants who complete the combined treatment and maintenance phase may continue receiving monotherapy treatment as extended maintenance for up to 10 additional cycles, provided there is no unacceptable toxicity, disease progression, or withdrawal of consent. ADI-PEG 20 treatment may continue for up to 104 weeks. After completing the 30-day toxicity evaluation period, participants will enter follow-up. Follow-up procedures will be documented under the PNOC COMP protocol, except for protocol-defined follow-up procedures. Participants will be followed under the PNOC COMP protocol until death or withdrawal from the study.
Participants with WT HGG will be treated at the recommended phase 2 dose (RP2D) of ADI-PEG 20 determined in Phase 1 in combination with TMZ. Participants who complete the combined treatment and maintenance phase may continue receiving monotherapy treatment as extended maintenance for up to 10 additional cycles, provided there is no unacceptable toxicity, disease progression, or withdrawal of consent. ADI-PEG 20 treatment may continue for up to 104 weeks.
Participants will receive injection of 36 mg/m\^2 of ADI-PEG 20 once weekly in the concomitant phase and maintenance phases given prior to the start of RT. Participants will also receive daily oral (PO) temozolomide (TMZ) with dosage based on age and dosing phase (concomitant, then maintenance) starting on the same day as Radiotherapy (RT). RT will be given in standard fractions (total dose 59.4 Gy) over 6 weeks. The boost volume, when present, will receive an additional 5.4 Gy for a total of 59.4 Gy. Post-RT, Participants will continue to receive weekly ADI-PEG 20 as monotherapy and then proceed to first cycle of maintenance therapy 28 days (+7 days) after completion of RT, in the absence of dose-limiting toxicities (DLT) or progressive disease. The maintenance phase consists of ten cycles (28 days long) of combination chemotherapy with ADI-PEG 20 and TMZ. Participants will receive no more than 104 weeks of ADI-PEG 20 therapy
Find a Clinic Near You
Who Is Running the Clinical Trial?
Sabine Mueller, MD, PhD
Lead Sponsor
Citations
Efficacy of arginine depletion by ADI-PEG20 in an intracranial ...
Monotherapy ADI-PEG20 significantly reduces the intracranial growth of ASS1 negative GBM and extends survival of mice carrying ASS1 negative GBM ...
2.
braintumourresearch.org
braintumourresearch.org/blogs/research-campaigning-news/adi-peg20-in-combination-with-radiotherapy?srsltid=AfmBOooyr13ESmkZO7t8WJa0qdLOOZTY4JjuySI4h4j4y1rHBlX6rA4SADI-PEG20 in combination with radiotherapy
“Laboratory results showed that, using the drug ADI-PEG20 in combination with radiotherapy, led to a durable response with extended disease-free survival with ...
Combination ADI-PEG 20, TMZ, and RT for Treatment of ...
To explore sex differences in arginine metabolism in participants with newly diagnosed high-grade glioma pre and post treatment with ADI-PEG 20.
Phase IB trial of pegylated arginine deiminase (ADI-PEG ...
ADI-PEG 20 has shown efficacy as monotherapy in ASS1 negative mouse glioblastoma (GBM) models and the combination of ADI-PEG 20 with ...
Therapeutic potential of arginine deprivation therapy for ...
In a mouse intracranial model, ADI-PEG20 effectively reduced peripheral blood arginine levels in as little as 48 h, significantly reduced intracranial growth ...
Combination ADI-PEG 20, TMZ, and RT for Treatment of ...
To explore sex differences in arginine metabolism in participants with newly diagnosed high-grade glioma pre and post treatment with ADI-PEG 20.
Therapeutic potential of arginine deprivation therapy for gliomas
ADI-PEG20 significantly reduces intracranial growth in ASS1-positive backgrounds. The combination of ADI and TMZ works on both positive and ...
8.
braintumourresearch.org
braintumourresearch.org/blogs/research-campaigning-news/adi-peg20-in-combination-with-radiotherapy?srsltid=AfmBOopTGa16IGfXAyAPQ3jLRLEsfbCnHIriehZ1AT1C-X0IZawK82zFADI-PEG20 in combination with radiotherapy
A drug which depletes the amino acid arginine made glioblastoma (GBM) tumours much more susceptible to radiotherapy.
Efficacy of arginine depletion by ADI-PEG20 in an ...
Monotherapy ADI-PEG20 significantly reduces the intracranial growth of ASS1 negative GBM and extends survival of mice carrying ASS1 negative GBM ...
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