What side effects are associated with this type of intervention?

The most common treatments for Low Grade Glioma (LGG) include selumetinib, an enzyme inhibitor, and the chemotherapy combination of carboplatin and vincristine. Selumetinib may cause side effects such as gastrointestinal issues, skin rash, and fatigue. Carboplatin and vincristine can lead to side effects including nausea, vomiting, neuropathy, and myelosuppression. Both treatment options aim to inhibit tumor growth but come with their respective adverse effects that need to be managed under medical supervision.

What prior FDA approvals exist?

As of now, there are no specific FDA approvals for enzyme inhibitors like Selumetinib for the treatment of Low-Grade Glioma (LGG). However, targeted therapies and enzyme inhibitors have been explored in various clinical trials for different types of gliomas. Selumetinib, which targets enzymes involved in cell growth, is currently being studied for its efficacy in treating LGG. Traditional treatments for LGG have included chemotherapy agents like carboplatin and vincristine, which work by stopping tumor cell growth and division.

What other types of research exist?

Promising novel alternatives to Selumetinib for Low Grade Glioma patients include other MEK inhibitors like Trametinib and Cobimetinib, as well as emerging therapies such as BRAF inhibitors (for patients with BRAF mutations), immune checkpoint inhibitors, and targeted therapies like everolimus. Clinical trials exploring these options should be considered for the most up-to-date treatment strategies.

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Alkylating Agent; Vinca Alkaloid

Selumetinib vs. Chemotherapy for Brain Cancer

Q: What is the mechanism of action of this treatment?

Selumetinib, a MEK inhibitor, blocks enzymes essential for cell growth, leading to tumor cell death. Carboplatin, a chemotherapy agent, causes DNA damage that prevents cell division, while vincristine disrupts microtubule formation, inhibiting cell division. These mechanisms are vital for Low Grade Glioma patients as they target specific pathways involved in tumor growth, potentially improving treatment efficacy and quality of life.

Phase 3

Recruiting

Led By Peter M de Blank

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows (performed within 7 days prior to enrollment): Age: Maximum Serum Creatinine (mg/dL) 2 to < 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female) 6 to < 10 years: 1 mg/dL (male); 1 mg/dL (female) 10 to < 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female) 13 to < 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female) >= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)

Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications)

Must not have

Current or past history of retinal vein occlusion or retinal detachment

Female patients who are pregnant are not eligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 10 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is comparing a new drug, selumetinib, with standard chemotherapy to treat patients with a specific type of brain tumor. The patients do not have a certain genetic mutation and are not affected by a genetic disorder. Selumetinib works by blocking enzymes needed for tumor growth, while the standard drugs kill or stop tumor cells from dividing.

Who is the study for?

This trial is for children and young adults aged 2 to 21 with low-grade glioma brain tumors without certain genetic mutations or neurofibromatosis. They should not have had previous tumor treatments except surgery, must be able to swallow capsules, and meet specific health criteria like normal organ function tests.

What is being tested?

The study compares the new drug Selumetinib against the standard chemotherapy drugs Carboplatin and Vincristine in treating low-grade gliomas. It aims to determine if Selumetinib is as effective as or better than standard treatment while also assessing its impact on quality of life.

What are the potential side effects?

Selumetinib may cause heart issues, vision changes, bleeding problems, high blood pressure, infections due to low white blood cell counts, liver problems indicated by blood tests, and fatigue. Standard chemo can cause nausea, hair loss, nerve damage leading to numbness or tingling sensations.

Eligibility Criteria

Inclusion Criteria

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

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My kidney function is within the required range for my age and gender.

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My blood pressure is 130/80 mmHg or lower, with or without medication.

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I am between 2 and 21 years old.

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My body surface area is at least 0.5 square meters.

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My tumor is still present or growing after diagnosis and I haven't had any treatment yet.

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My tumor can be measured and is at least 1 cm^2 in size.

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My heart's pumping ability is normal or above normal.

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I can take care of myself but may not be able to do active work.

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I can swallow whole capsules.

Exclusion Criteria

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

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I have had issues with my retina, like detachment or vein blockage.

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I am not pregnant and have taken a pregnancy test if capable of becoming pregnant.

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I do not have uncontrolled glaucoma or eye pressure above 22 mmHg.

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I agree to use effective birth control during and for 12 weeks after the study.

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I have or had central serous retinopathy.

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I do not have any infections that are not under control.

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My MRI shows a tumor in a specific part of my brain stem, making me ineligible.

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I have not been treated for another cancer besides surgery in the past year.

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I have heart failure that causes me symptoms.

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I have heart issues that affect my daily activities.

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I have severe heart valve disease.

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I have a history of irregular heartbeats.

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I am not taking vitamin E supplements above the daily recommended dose.

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I have not had chemotherapy, radiation, immunotherapy, or a bone marrow transplant for my cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 10 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 10 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 10 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Event-free survival (EFS)

Secondary study objectives

Change in executive function

Change in motor function

Change in quality of life (QOL)

+4 more

Other study objectives

Change in QOL scores over time

Change in neurocognitive functioning scores over time

Side effects data

From 2020 Phase 2 trial • 8 Patients • NCT03040986

100%

Aspartate aminotransferase increased

83%

Edema limbs

83%

Hypoalbuminemia

67%

Fatigue

67%

Hypertension

50%

Abdominal pain

50%

Anemia

50%

Dyspnea

50%

Alkaline phosphatase increased

50%

Anorexia

50%

Alanine aminotransferase increased

50%

Nausea

33%

Dizziness

33%

Hypocalcemia

33%

Generalized muscle weakness

33%

Hyponatremia

33%

Lymphocyte count decreased

33%

Rash maculo-papular

33%

Hypokalemia

33%

Bloating

33%

CPK increased

33%

Cough

33%

Creatinine increased

33%

Vomiting

17%

Heart failure

17%

Pancreatitis

17%

Diarrhea

17%

Dry mouth

17%

Colonic obstruction

17%

Confusion

17%

Gallbladder obstruction

17%

Gallbladder infection

17%

Lipase increased

17%

Serum amylase increased

17%

Ascites

17%

Dysgeusia

17%

Alopecia

17%

Edema trunk

17%

White blood cell decreased

17%

Atelectasis

17%

Dysphagia

17%

Glucose intolerance

17%

Hyperglycemia

17%

Weight loss

17%

Hypomagnesemia

17%

Hypotension

17%

Malaise

17%

Neck pain

17%

Pleural effusion

17%

Postnasal drip

17%

Renal and urinary disorders - Other, Dysuria

17%

Rash acneiform

17%

Neutrophil count decreased

17%

Paresthesia

17%

Peritoneal infection

17%

Back pain

17%

Biliary tract infection

17%

Blood bilirubin increased

17%

Fever

17%

Sore throat

17%

Urinary tract obstruction

17%

Musculoskeletal and connective tissue disorder - Other, muscle spasm

17%

Urine discoloration

100%

80%

60%

40%

20%

Study treatment Arm

Dose Level 0: 75mg Selumetinib Sulfate Twice Daily

75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm II (selumetinib sulfate)Experimental Treatment5 Interventions

Patients receive selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up.

Group II: Arm I (vincristine sulfate, carboplatin)Active Control6 Interventions

INDUCTION: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64, and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and magnetic resonance imaging (MRI) at baseline and end of induction. MAINTENANCE: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2030

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Selumetinib Sulfate

2017

Completed Phase 2

~80

0 / 23Eligibility 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

Selumetinib, a MEK inhibitor, blocks enzymes essential for cell growth, leading to tumor cell death. Carboplatin, a chemotherapy agent, causes DNA damage that prevents cell division, while vincristine disrupts microtubule formation, inhibiting cell division. These mechanisms are vital for Low Grade Glioma patients as they target specific pathways involved in tumor growth, potentially improving treatment efficacy and quality of life.