PTC596 + Radiotherapy for Brain Tumor

Recruiting at 9 trial locations

Overseen By Leonie Mikael, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Nationwide Children's Hospital

Must not be taking: Investigational drugs, Anticancer agents

Disqualifiers: Pregnancy, Oligodendroglioma, Uncontrolled infection, others

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

Compensation: Varies

Number of Visits: Unknown

64 Participants Needed

Trial Summary

Do I need to stop taking my current medications for the trial?

Yes, you may need to stop taking certain medications. The trial does not allow participants to take other anti-cancer agents, investigational drugs, enzyme-inducing anticonvulsants, rifampin, medications that prolong the QTc interval, CYP1A2 inhibitors like duloxetine, alosetron, or theophylline, beta-blockers, and therapeutic anticoagulants. Some SSRIs should be used with caution.

What data supports the effectiveness of the treatment PTC596 + Radiotherapy for Brain Tumor?

Research on similar treatments, like the use of radiosensitizers such as motexafin gadolinium and pentoxifylline, suggests that combining certain drugs with radiation therapy can enhance the effectiveness of radiation in treating brain tumors. These studies indicate that using additional agents alongside radiation may improve outcomes for patients with brain metastases. ^{1 2 3 4 5}

Is PTC596 with radiotherapy safe for humans?

The safety of radiotherapy (also known as radiation therapy or external beam radiation therapy) has been studied in various conditions, showing that while it can be effective, it may cause side effects depending on the area treated and the dose. For example, in prostate cancer, it is generally considered safe but can have early and late side effects. However, specific safety data for PTC596 combined with radiotherapy for brain tumors is not available in the provided research. ^{6 7 8 9 10}

What makes the PTC596 + Radiotherapy treatment for brain tumors unique?

The PTC596 + Radiotherapy treatment is unique because it combines a novel drug, PTC596, with radiotherapy to potentially enhance the effectiveness of radiation in treating brain tumors. This combination aims to improve outcomes by using PTC596 to sensitize the tumor to radiation, which is different from standard treatments that typically involve only radiotherapy or other drugs that may not have this sensitizing effect. ^{1 11 12 13 14}

What is the purpose of this trial?

The goal of this study is to evaluate the safety of the study drug PTC596 (Unesbulin) taken in combination with radiotherapy (RT) when given to pediatric patients newly diagnosed with High-Grade Glioma (HGG) including diffuse intrinsic pontine glioma (DIPG). The main aims of the study are to: * Find the safe dose of the study drug PTC596that can be given without causing serious side effects. * Find out the amount of drug that enters blood (in all patients) and tumor (in patients who receive drug prior to a planned surgery for removal of their brain tumor) During the first cycle (6-7weeks), patients will receive drug orally twice a week in combination with daily RT. During subsequent cycles (4 weeks each), they will receive only the study drug orally twice a week. Funding Source - FDA OOPD

Research Team

Margot Lazow, MD

Principal Investigator

Nationwide Children's Hospital

Maryam Fouladi, MD

Principal Investigator

Nationwide Children's Hospital

Patricia Baxter, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for children and young adults aged between 1 and 21 with newly diagnosed high-grade gliomas, including DIPG. They must be able to swallow pills, have not had cancer treatment before, and their organs must function well. Those with certain other health issues or who can't follow the study rules are excluded.

Inclusion Criteria

I have been recently diagnosed with a high-grade glioma that is not in my brainstem.

I have a new diagnosis of DIPG and my doctor recommends a biopsy.

I have been diagnosed with a specific brain tumor called DIPG without needing a tissue sample.

Exclusion Criteria

Patients of childbearing or child fathering potential who have not agreed to use an effective contraceptive method

My cancer is related to HIV or a solid organ transplant.

Patients currently receiving another investigational drug

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Initial Cycle

Participants receive PTC596 orally twice weekly in combination with daily radiotherapy for 6-7 weeks

6-7 weeks

Daily visits for radiotherapy

Treatment - Maintenance Cycles

Participants continue with maintenance therapy receiving PTC596 orally twice weekly for up to 26 cycles

Up to 24 months

Surgical Cycle

For surgical cohort, PTC596 is administered prior to biopsy or re-resection, followed by radiotherapy and maintenance therapy

2 weeks before RT

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• PTC596
• Radiotherapy

Trial Overview The safety of PTC596 (Unesbulin) combined with radiotherapy is being tested in pediatric patients with brain tumors like DIPG. The study aims to find a safe drug dose that doesn't cause serious side effects and to measure how much drug gets into the blood and tumor.

Participant Groups

Group I: Treatment (PTC596) Experimental Treatment 2 Interventions

PTC596 administered orally twice weekly (M/Th or T/F schedule) concomitantly with RT for 6 -7 weeks. Each subsequent cycle is defined as 28 days. Post RT patients will continue to receive PTC596 twice weekly for up to 26 cycles at RP2D of 200mg/m2 with a maximum dose capped at 400mg for patients with BSA ≥2.0

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

PTC Therapeutics

Industry Sponsor

Trials

75

Recruited

6,300+

Dr. Matthew B. Klein

PTC Therapeutics

Chief Executive Officer since 2023

BA from the University of Pennsylvania, MD from Yale University School of Medicine, MS in Epidemiology from the University of Washington School of Public Health

Dr. Stuart W. Peltz

PTC Therapeutics

Chief Medical Officer since 2023

MD from Harvard Medical School

Findings from Research

In a phase II trial involving 14 patients with brain metastases, the combination of pentoxifylline (PTX) and standard whole-brain radiation treatment (WBRT) showed a median survival time of 33 days, which aligns with historical control data.

The study indicated that PTX was well-tolerated, as toxicity was not a common reason for patients dropping out, suggesting that higher doses of PTX could be explored in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II evaluation of pentoxifylline combined with radiation in the treatment of brain metastases. Johnson, FE., Harrison, BR., McKirgan, LW., et al.[2013]

Motexafin gadolinium (MGd) is a novel radiation sensitizer that may improve the effectiveness of whole brain radiation therapy (WBRT) for patients with brain metastases from non-small cell lung cancer (NSCLC).

Current outcomes for NSCLC patients undergoing WBRT are poor, with median survival times only in months, highlighting the need for effective treatments like MGd to enhance therapeutic results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motexafin gadolinium injection for the treatment of brain metastases in patients with non-small cell lung cancer. Thomas, SR., Khuntia, D.[2019]

In a study of 23 patients with high-risk prostate cancer, stereotactic body radiation therapy (SBRT) was found to be feasible and well tolerated, with low rates of severe gastrointestinal (GI) and genitourinary (GU) toxicities.

The treatment resulted in acute grade 1 GI toxicities in only 9.1% of patients and grade 3 GU toxicities in 4.5%, indicating that serious side effects were uncommon, but further long-term follow-up is needed to assess ongoing safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Tolerance Outcomes of Stereotactic Hypofractionated Accelerated Radiation Therapy Concomitant with Pelvic Node Irradiation in High-risk Prostate Cancer. Pinitpatcharalert, A., Happersett, L., Kollmeier, M., et al.[2022]

In a phase I/II trial involving 75 patients with brain metastases, the combination of whole-brain radiotherapy (WBRT) and the chemotherapy drug topotecan showed a promising overall response rate of 72%, indicating potential effectiveness in this challenging patient population.

The study found that the recommended dosage of topotecan was 0.4 mg/m²/day due to higher toxicity at 0.5 mg/m²/day, with moderate side effects occurring in 19% of patients, suggesting that while the treatment is effective, careful monitoring of toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II trial of topotecan and radiation therapy for brain metastases in patients with solid tumors. Hedde, JP., Neuhaus, T., Schüller, H., et al.[2013]

In early phase I studies, patients undergoing 252Cf brachytherapy combined with whole brain photon beam therapy tolerated the treatment well and showed improvements in performance status and reductions in tumor size as evaluated by CT scans.

The study highlighted the need for individualized treatment plans due to the large size of tumors and significant brain edema, indicating that high-dose external beam irradiation is necessary for effective responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interstitial 252Cf neutron therapy for glioblastoma multiforme. Maruyama, Y., Chin, HW., Young, AB., et al.[2019]

In a study of 260 patients treated for brain and skull base tumors with photon and particle therapies, no unexpected severe toxicities were reported, indicating a favorable safety profile for these treatments.

The use of particle therapy, particularly protons and carbon ions, shows promise in potentially reducing the risk of secondary malignancies and improving neurocognitive outcomes, although longer follow-up is needed to confirm these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base. Combs, SE., Kessel, K., Habermehl, D., et al.[2016]

References

1. Greece pubmed.ncbi.nlm.nih.gov

A phase II evaluation of pentoxifylline combined with radiation in the treatment of brain metastases. [2013]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Motexafin gadolinium injection for the treatment of brain metastases in patients with non-small cell lung cancer. [2019]

3. Japan pubmed.ncbi.nlm.nih.gov

[Clinical evaluation for radiotherapy of metastatic brain tumors in lung cancer: prognostic analyses relevant to QOL]. [2006]

4. Brazil pubmed.ncbi.nlm.nih.gov

Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer. [2018]

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

Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Français de Pneumo-Cancérologie (GFPC) Protocol 95-1. [2020]

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

Early Tolerance Outcomes of Stereotactic Hypofractionated Accelerated Radiation Therapy Concomitant with Pelvic Node Irradiation in High-risk Prostate Cancer. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Feasibility and safety of 1.5 T MR-guided and daily adapted abdominal-pelvic SBRT for elderly cancer patients: geriatric assessment tools and preliminary patient-reported outcomes. [2020]

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

Avoiding Toxicity With Lung Radiation Therapy: An IASLC Perspective. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Linac-based stereotactic body radiation therapy for low and intermediate-risk prostate cancer : Long-term results and factors predictive for outcome and toxicity. [2020]

10. Greece pubmed.ncbi.nlm.nih.gov

Bladder and rectal toxicity of BeamCath application in radiotherapy of prostate cancer. [2015]

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

A phase I/II trial of topotecan and radiation therapy for brain metastases in patients with solid tumors. [2013]

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

A study on different therapies and prognosis-related factors for 101 patients with SCLC and brain metastases. [2020]

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

Interstitial 252Cf neutron therapy for glioblastoma multiforme. [2019]

14. England pubmed.ncbi.nlm.nih.gov

Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base. [2016]