What side effects are associated with this type of intervention?

Common treatments for Glioblastoma, including chemotherapy (e.g., temozolomide), radiation therapy, and targeted therapies, often have a range of side effects. Chemotherapy can cause nausea, vomiting, fatigue, and increased risk of infections due to bone marrow suppression. Radiation therapy may lead to hair loss, skin irritation, and cognitive changes. Targeted therapies, such as metalloproteinase inhibitors like INCB7839, can cause side effects including fatigue, gastrointestinal issues, and potential impacts on liver function. It is important to discuss these potential side effects with a healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for glioblastoma, including temozolomide, an oral alkylating agent, and bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF). These treatments focus on inhibiting tumor growth and angiogenesis. While specific metalloproteinase inhibitors like INCB7839 targeting ADAM10 have not been highlighted in the context provided, ongoing research and clinical trials continue to explore novel mechanisms, including metalloproteinase inhibition, to improve outcomes for glioblastoma patients.

What other types of research exist?

Promising novel alternatives to INCB7839 for glioblastoma patients include: 1) Dovitinib, a multikinase inhibitor that downregulates stem cell proteins and inhibits STAT3 phosphorylation, showing efficacy in glioblastoma cells. 2) Immune checkpoint inhibitors such as pembrolizumab and nivolumab, which have shown potential in treating various cancers, including glioblastoma, by enhancing the immune response against tumor cells. 3) Proteasome inhibitors like MLN9708/2238, which induce apoptosis and cell cycle arrest in osteosarcoma cells and may have similar effects in glioblastoma. These alternatives offer different mechanisms of action and have shown promise in preclinical or clinical settings.

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Monoclonal Antibodies

INCB7839 for Brain Cancer in Children

Phase 1

Waitlist Available

Research Sponsored by Pediatric Brain Tumor Consortium

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Off all colony-forming growth factors for at least 7 days

Failed at least 1 standard tumor-directed treatment besides surgery

Must not have

Significant family history of thrombosis in first-degree relatives

History of non-central line related thrombosis or clotting-promoting disorders

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years following last dose of incb7839.

Awards & highlights

No Placebo-Only Group

Summary

This trial tests INCB7839, a drug that blocks proteins helping cancer cells grow, on children with tough-to-treat brain tumors that have returned or grown after initial treatment. The drug works by stopping a protein needed for tumor growth from being released.

Who is the study for?

This trial is for children aged 3-21 with recurrent or progressive high-grade brain tumors who can swallow pills. They must have measurable disease, be recovered from prior treatments, and have stable health conditions. Those with controlled seizures or neurological deficits may qualify. Patients on birth control and HIV-positive individuals under certain criteria are also eligible.

What is being tested?

The trial tests INCB7839 in children with high-grade gliomas that came back or got worse after initial treatment. It's a phase 1 study to see how safe the drug is and how it affects these types of brain tumors.

What are the potential side effects?

While specific side effects for INCB7839 aren't listed, common ones for cancer drugs include nausea, fatigue, blood count changes increasing infection risk, liver function issues, allergic reactions, and potential bleeding problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I haven't taken any growth factor medications for over a week.

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I have tried at least one cancer treatment other than surgery and it didn't work.

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My neurological symptoms have not changed for at least a week.

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My brain tumor is aggressive and has come back or gotten worse.

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I am between 3 and 21 years old.

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My dose of dexamethasone has been stable or decreasing for the last week.

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My body surface area fits within the required range for my medication dose.

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I am between 3 and 21 years old.

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I can do most activities but may need assistance.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My close family has a history of blood clots.

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I have had blood clots not related to a central line.

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I have not had significant new brain bleeding shown on an MRI in the last 2 weeks.

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I do not have any other type of cancer.

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I have a known bleeding or clotting disorder.

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I can attend all follow-up visits and stick to the study plan.

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My high blood pressure is not under control.

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I cannot receive blood clot prevention treatments.

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I am not on any other cancer treatments or experimental drugs.

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I use birth control that contains estrogen.

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I have had bleeding in my brain from a tumor.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years following last dose of incb7839.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years following last dose of incb7839.

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years following last dose of incb7839. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose (MTD) and/or recommend Phase II dose (RP2D) of INCB7839.

To characterize the apparent oral clearance [CL/F] of INCB7839 administered on this schedule in children with recurrent/progressive high-grade glioma.

To characterize the area under the plasma concentration versus time curve (AUC) of INCB7839 administered on this schedule in children with recurrent/progressive high-grade glioma.

+3 more

Secondary study objectives

To make a preliminary assessment of duration of response in children with recurrent/progressive high-grade glioma.

To make a preliminary assessment of overall survival in children with recurrent/progressive high-grade glioma.

To make a preliminary assessment of progression-free survival in children with recurrent/progressive high-grade glioma.

Other study objectives

ADAM10 inhibition of HER2 extracellular domain in serum.

To assess and monitor ADAM10 inhibition of neuroligin-3 (NLGN3) in cerebral spinal fluid.

To characterize the maximum concentration [CMAX] of INCB7839 in cerebrospinal fluid.

Side effects data

From 2019 Phase 1 & 2 trial • 30 Patients • NCT02141451

50%

Lymphocyte count decreased

25%

Platelet count decreased

25%

Dysphagia

25%

Pain

25%

Anemia

25%

Nausea

25%

White blood cell decreased

25%

Neutrophil count decreased

100%

80%

60%

40%

20%

Study treatment Arm

INCB7839 200 mg (Phase I)

INCB7839 300 mg (Phase I)

INCB7839 300 mg (Phase II)

INCB7839 100 mg (Phase I)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Dose-findingExperimental Treatment1 Intervention

INCB7839 dosing will begin at 120 mg/m2/dose BID which is equivalent to the adult RP2D (200 mg PO BID) based on a typical adult size of 1.67m2. The INCB7839 dose may be decreased to 80 mg/m2/dose BID if the staring dose is not tolerable. 28 consecutive days (4 weeks) will constitute one course. Patients may continue to receive INCB7839 for 26 courses (approximately 2 years).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

INCB7839

2014

Completed Phase 2

~30

0 / 20Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Glioblastoma include surgery, radiation therapy, and chemotherapy. Chemotherapy agents like temozolomide work by damaging the DNA of cancer cells, leading to cell death. Targeted therapies, such as INCB7839, inhibit metalloproteinases like ADAM10, which are involved in the shedding of cell surface proteins and may contribute to tumor progression and metastasis. These mechanisms are crucial for Glioblastoma patients as they aim to reduce tumor growth, prevent metastasis, and improve survival rates by targeting specific pathways involved in cancer cell proliferation and spread.