Selumetinib Clinical Trials

What Is Selumetinib?

Selumetinib is an FDA-approved medication for children 2 years of age and older with Neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). This approval was based on clinical findings that selumetinib helps to shrink plexiform neurofibromas, which are tumors known to cause significant health problems in children with NF1. Beyond its approved use, selumetinib is also being investigated in a wide range of clinical trials for other conditions, including various solid tumors, low grade glioma, and melanoma.

There have been 99 clinical trials involving selumetinib, with a total enrollment of 14,325 participants. The first trial began on 2007-10-30, and the latest is expected to conclude on 2025-01-08. Currently, 6 trials are recruiting new participants, while 51 trials have been completed. Key organizations sponsoring these studies include the National Cancer Institute (NCI) and AstraZeneca.

Uses and Conditions Under Study

Selumetinib is primarily studied for its effects on various types of cancer and tumor-related conditions. Its FDA approval is for children with Neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). NF1 is a genetic disorder that can lead to tumor growth, and plexiform neurofibromas are a specific type of tumor that can cause significant health issues. Selumetinib has been shown to shrink these tumors. A total of 18 trials have specifically investigated selumetinib for Neurofibromatosis 1, Neurofibromatosis Type 1, and Plexiform Neurofibroma.

Beyond NF1, selumetinib is also being explored for its potential in treating various solid tumors. These include general solid tumors, recurrent malignant solid neoplasms, advanced malignant solid neoplasms, and refractory malignant solid neoplasms. These conditions involve the growth of abnormal tissue that can be difficult to treat. Selumetinib is being investigated to see if it can help manage or reduce the size of these tumors. Across these categories, selumetinib has been studied in 15 trials.

More specifically, selumetinib is under investigation for several distinct cancers. For example, it is being studied for low grade glioma, a type of brain tumor. It is also being researched for recurrent melanoma, a serious form of skin cancer that has returned, and for non-small cell lung cancer, a common type of lung cancer. These studies aim to determine if selumetinib can offer new treatment options for patients with these challenging diseases. There are 9 trials focusing on these specific cancer types.

Dosing

Selumetinib is typically administered as an oral capsule. The FDA-approved dose for pediatric patients 2 years of age and older with symptomatic, inoperable plexiform neurofibromas associated with NF1 is 25 mg/m2/dose taken twice daily (BID). This dose is calculated based on the patient's body surface area.

In clinical trials, various other dosages and regimens have been investigated, often in combination with other drugs or for different conditions. These investigational doses have ranged from 20 mg to 125 mg. For example, some studies have explored daily oral capsules at 20-50 mg twice daily, while others have tested single doses of 75 mg or 75 mg twice daily. Some trials have also examined doses of 100 mg or 125 mg taken once daily (OD). Dosing may also vary depending on whether the medication is taken on an empty stomach or with food, as indicated by studies examining 75 mg oral capsules taken both fasted and fed. The specific dose and schedule depend on the study protocol and the condition being investigated.

Side Effects

When taking Selumetinib, patients may experience various side effects. The most common side effect reported was diarrhea, which affected 49.5% of patients taking Selumetinib, compared to 26.7% of those on placebo. Other common side effects, listed in order of frequency, included:

• Nausea: 32.1% of patients on Selumetinib experienced nausea, compared to 21.1% on placebo.
• Rash: 30.2% of patients taking Selumetinib developed a rash, while 10.8% on placebo did.
• Peripheral swelling (oedema peripheral): 24.8% of patients on Selumetinib experienced swelling, compared to 11.4% on placebo.
• Acne-like skin inflammation (dermatitis acneiform): 24.1% of patients taking Selumetinib developed this condition, significantly higher than 3.3% on placebo.
• Weakness or lack of energy (asthenia): 21.7% of patients on Selumetinib reported asthenia, compared to 16.2% on placebo.
• Vomiting: 21.1% of patients experienced vomiting with Selumetinib, versus 9.4% on placebo.
• Sore mouth or inflammation (stomatitis): 19.1% of patients on Selumetinib reported stomatitis, compared to 10.0% on placebo.

Clinical Trial Results

Clinical trials have evaluated Selumetinib for various cancer types. Here are some key findings:

Recurrent Low-Grade Ovarian Cancer or Peritoneum Cancer

In a study (NCT00551070) involving women with recurrent low-grade ovarian or peritoneum cancer, patients treated with Selumetinib had a median overall survival of 32.4 months. The median progression-free survival was 11.3 months, meaning patients lived for this duration without their cancer worsening. An objective tumor response, indicating a reduction in tumor size, was observed in 15.4% of patients.

Biliary Cancer That Cannot Be Removed By Surgery

For patients with advanced biliary cancer (NCT00553332), treatment with Selumetinib resulted in a median progression-free survival of 3.7 months. The median overall survival was 9.8 months. An objective response, where tumors shrank or disappeared, was seen in 10% of patients (3 out of 30 participants).

Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

A study (NCT00559949) in patients with papillary thyroid cancer that was resistant to radioactive iodine treatment showed a median progression-free survival of 32 weeks (approximately 7.4 months). An objective response was observed in 5% of participants (1 out of 20 participants).

Recurrent or Refractory Acute Myeloid Leukemia

In a trial (NCT00588809) for patients with recurrent or refractory acute myeloid leukemia, Selumetinib demonstrated a response rate of 16.67% in subjects without a specific FLT3 ITD gene mutation.

Locally Advanced or Metastatic Liver Cancer

For patients with locally advanced or metastatic liver cancer (NCT00604721), treatment with Selumetinib led to a median overall survival of 4.2 months and a median progression-free survival of 1.4 months. No participants in the safety cohort (0 out of 20) achieved a radiographic objective response.

Currently Recruiting Trials

Where to Participate

• Chicago, Illinois (16 sites)
• Honolulu, Hawaii (13 sites)
• Columbus, Ohio (12 sites)
• Houston, Texas (10 sites)
• St Louis, Missouri (10 sites)
• Philadelphia, Pennsylvania (9 sites)
• Richmond, Virginia (9 sites)
• Dayton, Ohio (8 sites)
• Flint, Michigan (8 sites)
• Des Moines, Iowa (7 sites)

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