21 Participants Needed

SARC031: MEK Inhibitor Selumetinib (AZD6244) in Combination With the mTOR Inhibitor Sirolimus for Patients With Malignant Peripheral Nerve Sheath Tumors

Recruiting at 4 trial locations
SO
Overseen BySARC Office
Age: Any Age
Sex: Any
Trial Phase: Phase 2
Sponsor: Sarcoma Alliance for Research through Collaboration
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This trial tests a combination of two oral medications, selumetinib and sirolimus, for patients with severe NF1-related or sporadic tumors that cannot be removed by surgery or have spread. The drugs work together to block cancer growth signals and stop cell multiplication.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but you cannot take other anti-cancer agents or certain medications that affect specific enzymes and transporters. There are also restrictions on using certain foods and supplements like grapefruit and St. John's Wort.

What data supports the effectiveness of the drug Selumetinib?

Selumetinib, when combined with another drug called docetaxel, has been shown to improve survival and response rates in patients with a specific type of lung cancer (KRAS mutant non-small-cell lung cancer).12345

What safety data exists for Selumetinib (also known as AZD6244, ARRY-142886) in humans?

Selumetinib has been studied in healthy volunteers and patients with various cancers, showing it is generally well-tolerated, but long-term safety data is not fully described. It has been tested in combination with other treatments, and while it shows promise, the full range of potential side effects over time is still being researched.12678

How is the drug Selumetinib unique compared to other treatments?

Selumetinib is unique because it is an oral drug that specifically targets and inhibits MEK1/2, which are proteins involved in cell growth and survival, making it potentially effective for various tumor types. This targeted approach is different from traditional chemotherapy, which affects both cancerous and healthy cells.12369

Research Team

BW

Brigitte Widemann, MD

Principal Investigator

National Cancer Institute (NCI)

AK

AeRang Kim, MD, PhD

Principal Investigator

Children's National Research Institute

Eligibility Criteria

Inclusion Criteria

You have a type of cancer called MPNST that cannot be removed with surgery or has spread to other parts of the body.
Age ≥ 12 years of age
Patients must have measureable disease by RECIST
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Exclusion Criteria

Patients who cannot swallow whole pills
Patients should not receive immunizations with attenuated live vaccines within four weeks of study entry or during study period
Patients who any known severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: Severely impaired lung function defined as spirometry and DLCO that is 50% of the normal predicted value corrected for hemoglobin and alveolar volume and/or O2 saturation that is 88% or less at rest on room air. For patients who do NOT have respiratory symptoms (e.g. dyspnea at rest, known requirement for supplemental oxygen), pulmonary function test is not required
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Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive selumetinib and sirolimus orally, with selumetinib given at 50mg twice daily and sirolimus at 4mg once daily, with a cycle 1 day 1 loading dose of 12mg. Each cycle is 28 days.

Up to 6 months

Follow-up

Participants are monitored for safety, effectiveness, and progression-free survival after treatment

Up to 4 years

Treatment Details

Interventions

  • Selumetinib
  • Sirolimus
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Selumetinib and SirolimusExperimental Treatment2 Interventions
A Simon's two-stage phase 2 trial of MEK inhibitor selumetinib in combination with the mTOR inhibitor sirolimus to determine the safety and clinical benefit in patients with unresectable or metastatic MPNSTs. Both agents will be given orally on an empty stomach. Selumetinib will be given orally at a dose of 50mg twice daily continuously. Sirolimus will be given orally at a dose of 4mg once daily with a cycle 1 day 1 loading dose of 12mg. Each cycle will be considered 28 days.

Selumetinib is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Koselugo for:
  • Neurofibromatosis type 1 (NF1) in pediatric patients 2 years of age and older with symptomatic, inoperable plexiform neurofibromas (PN)
🇪🇺
Approved in European Union as Koselugo for:
  • Neurofibromatosis type 1 (NF1) in pediatric patients 2 years of age and older with symptomatic, inoperable plexiform neurofibromas (PN)

Find a Clinic Near You

Who Is Running the Clinical Trial?

Sarcoma Alliance for Research through Collaboration

Lead Sponsor

Trials
26
Recruited
2,000+

AstraZeneca

Industry Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

United States Department of Defense

Collaborator

Trials
940
Recruited
339,000+

References

Metabolism, Excretion, and Pharmacokinetics of Selumetinib, an MEK1/2 inhibitor, in Healthy Adult Male Subjects. [2019]
Comparison of the Pharmacokinetics of the Phase II and Phase III Capsule Formulations of Selumetinib and the Effects of Food on Exposure: Results From Two Randomized Crossover Trials in Healthy Male Subjects. [2022]
Identification of common predictive markers of in vitro response to the Mek inhibitor selumetinib (AZD6244; ARRY-142886) in human breast cancer and non-small cell lung cancer cell lines. [2021]
Temsirolimus in VEGF-refractory metastatic renal cell carcinoma. [2020]
Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer. [2018]
Population pharmacokinetics of the MEK inhibitor selumetinib and its active N-desmethyl metabolite: data from 10 phase I trials. [2021]
Selumetinib in the treatment of non-small-cell lung cancer. [2018]
A long-term surviving patient with recurrent low-grade serous ovarian carcinoma treated with the MEK1/2 inhibitor, selumetinib. [2022]
A phase I dose-escalation study of selumetinib in combination with docetaxel or dacarbazine in patients with advanced solid tumors. [2018]