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Malignant Peripheral Nerve Sheath TumorsPhase 2NCT03433183

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

A Phase 2 study testing Selumetinib and Sirolimus in people with Malignant Peripheral Nerve Sheath Tumors and Neurofibromatosis 1, run by Sarcoma Alliance for Research through Collaboration at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

To determine the clinical benefit rate of selumetinib in combination with sirolimus in patients with unresectable or metastatic neurofibromatosis type 1 (NF1) associated or sporadic MPNST. Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Selumetinib and Sirolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
5 sitesUnited States
Study dates
2 Oct 2019to 1 Oct 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age ≥ 12 years of age
  • Patients with unresectable or metastatic histologically confirmed sporadic or NF1 associated MPNST.
  • Patients must have measureable disease by RECIST.
  • Patients must have experienced progression after one or more prior regimens of cytotoxic chemotherapy. Patients who have refused cytotoxic chemotherapy or for whom treatment on this protocol prior to receiving cytotoxic chemotherapy is felt to be in the best interest for the patient by the local investigator will also be eligible.
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering on this study.
  • No limitation on the number of prior chemotherapy regimens that the patient may have received prior to study entry.
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  • The last dose of all myelosuppressive anticancer drugs must be at least 3 weeks prior to study entry.
  • The last dose of immunotherapy (monoclonal antibody or vaccine) must be at least 4 weeks prior to study entry.
  • The last dose of all biologic agents for the treatment of the patient's cancer (such as retinoids or tyrosine kinase inhibitors) must be at least 7 days prior to study entry.
  • The last dose of radiation to more than 25% of marrow containing bones (pelvis, spine, skull) must be at least 4 weeks prior to study entry. The last dose of all other local palliative (limited port) radiation must be at least 2 weeks prior to study entry.
  • At least 2 months post-autologous stem cell transplant or at least 3 months post-allogeneic transplant and recovered from toxicities without evidence of graft versus host disease and on stable doses of immunosuppressive medications if required.
  • The last dose of colony stimulating factors, such as filgrastim, sargramostim, and erythropoietin, must be at least 1 week prior to study entry, the last dose of long-acting colony stimulating factors, such as pegfilgrastim, must be at least 2 weeks prior to study entry.
  • No other anti-cancer therapy (chemotherapy, biological therapy, radiation therapy) is permitted.
  • Karnofsky performance level ≥ 50%.
  • Patients who are unable to walk because of paralysis or motor weakness, but who are up in a wheelchair will be considered ambulatory for the purpose of calculating the performance score.
  • Peripheral absolute neutrophil count (ANC) of ≥1000/μL
  • Platelet count ≥75,000/μL (transfusion independent (no transfusion within at least 7 days prior to enrollment)
  • Total bilirubin must be ≤ 1.5 times the upper limit of normal (ULN)
  • SGPT (ALT) must be ≤ 3.0 times ULN
  • Serum creatinine ≤ ULN or creatinine clearance >60 ml/min/1.73 m2
  • Serum triglyceride level ≤300 mg/dL and serum cholesterol level ≤ 300 mg/dL (Patient may be on lipid-lowering medicine)
  • Normal ejection fraction by ECHO or cardiac MRI >55%
  • QTcF ≤ 450ms
  • Fertile men and women of childbearing potential must agree to use an effective method of birth control.
  • Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease and are without evidence of clinical progression or stable disease at 4 weeks.

Who cannot join

  • Patients receiving other anti-cancer agents are not eligible.
  • Patients who cannot swallow whole pills.
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (for example cyclosporine). Topical or inhaled corticosteroids are allowed.
  • Patients should not receive immunizations with attenuated live vaccines within four weeks of study entry or during study period.
  • Any recent major surgery within a minimum of 4 weeks, with the exception of surgical placement for vascular access, or minor surgery (excluding tumor biopsies) within 14 days.
  • Patients who any known severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
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  • 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.
  • Cardiac conditions as follows:
  • Uncontrolled hypertension (blood pressure ≥150/95 mmHg despite medical therapy).
  • Acute coronary syndrome within 6 months prior to starting treatment
  • Uncontrolled angina despite medical therapy
  • Symptomatic heart failure NYHA Class II-IV prior or current cardiomyopathy, or severe valvular disease
  • Prior or current cardiomyopathy
  • Uncontrolled Type 1 or 2 diabetes as defined by fasting serum glucose >1.5 x ULN
  • Uncontrolled infection
  • Pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome, or renal tubular acidosis.
  • Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of small bowel, symptomatic inflammatory bowel disease, or ulcerative colitis, or partial or complete bowel obstruction.
  • Ophthalmological conditions as follows:
  • Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion
  • Intraocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma
  • Supplementation with vitamin E greater than 100% of the daily recommended dose.
  • Hypersensitivity to active or inactive excipients of rapamycins (sirolimus, temsirolimus or everolimus) or selumetinib or drugs with similar chemical structures or class to sirolimus or selumetinib.
  • Patients unwilling or unable to comply with the protocol.
  • Seville orange, star fruit, grapefruit and their juices, and St. John's Wort use are not allowed while on study.
  • Exposure to strong or moderate inhibitors or inducers of CYP3A4/5, Pgp (MDR1) and BCRP if taken within the stated washout periods before the first dose of study treatment.
  • Exposure to specific substrates of drug transporters OATP1B1, OATP1B3, MATE1 and MATE2K within the appropriate washout periods (a minimum of 5 x reported elimination half-life) before the first dose of study treatment.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • National Cancer Institute

    Bethesda, Maryland, 20892

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Washington University

    St Louis, Missouri, 63110

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: SARC031: A Phase 2 Trial of the MEK Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Combination With the mTOR Inhibitor Sirolimus for Patients With Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumors

To determine the clinical benefit rate of selumetinib in combination with sirolimus in patients with unresectable or metastatic neurofibromatosis type 1 (NF1) associated or sporadic MPNST.

Read the detailed description
  1. Primary Objective
  • To determine the clinical benefit rate of selumetinib in combination with sirolimus in patients with unresectable or metastatic NF1 associated or sporadic MPNST

II. Secondary Objective(s)

  • To define and describe the toxicities of selumetinib in combination with sirolimus in patients with unresectable or metastatic NF1 associated or sporadic MPNST.
  • To assess the impact on intensity and pain interference and correlate to changes in clinical, imaging response and progression
  • To assess progression free and overall survival

Selumetinib will be given orally 50mg twice daily continuously and sirolimus will be given orally 4mg once daily with a cycle 1 day 1 loading dose of 12mg. One cycle will be 28 days. Patients will be able to remain on treatment as long as they do not experience progressive disease or unacceptable toxicity. Stage 1 will require 7 patients, with no further accrual if 0 of 7 respond. If 1 or greater of the 7 patients respond, accrual will continue until 21 patients have been enrolled.

Being tested
Selumetinib, Sirolimus
Medical subject headings
Neurofibrosarcoma, Neurofibromatosis 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SelumetinibDrug

    Also called AZD6244

    Selumetinib (AZD6244) is an oral selective inhibitor of the mitogen-activated protein kinase (MEK) 1/2 currently in development for adult malignancies, pediatric low-grade gliomas and NF1 plexiform neurofibromas. MEK is a critical kinase in the mitogen activated protein (MAP) kinase signal transduction pathway for many growth factor receptors that provide growth signals to cancer cells.

  • SirolimusDrug

    Also called Rapamycin

    Sirolimus is a macrocyclic lactone produced by Streptomyces hygroscopicus and inhibitor of mammalian Target of Rapamycin (mTOR) serine threonine kinase, which plays a critical role in regulating cellular energy sensing, growth and metabolism.

Study groups in NCT03433183
Study groupRoleWhat they receive
Selumetinib and SirolimusExperimentalA 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.
Receives: Drug: Selumetinib; Drug: Sirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical Benefit Rate of Selumetinib in Combination With Sirolimus in Patients With Unresectable or Metastatic NF1 Associated or Sporadic MPNST.

    An evaluable patient will be classified as a responder if the patient achieves a partial response (PR), complete response (CR) or stable disease (SD) ≥ 4 cycles.

    Measured: Up to 6 months

Secondary outcomes (4)

  1. Progression Free (PFS) and Overall Survival (OS)

    Determined using the Kaplan-Meier method with PFS at important time points reported along with 95% two sided confidence intervals.

    Measured: PFS is the duration of time from the start of treatment to the time of objective progression or death whichever happens first up to 4 years. OS is the duration of time from the start of treatment to the time of death; assessed up to 4 years.

  2. Define and Describe the Toxicities of Selumetinib in Combination With Sirolimus in Patients With Unresectable or Metastatic NF1 Associated or Sporadic MPNST.

    Treatment-emergent adverse events occurring after initiation of selumetinib in combination with sirolimus were assessed and graded according to CTCAE v5.0. The safety population included all participants who received at least one dose of study treatment.

    Measured: Up to 6 months

  3. Assess the Impact on Pain Interference

    Change in Pain Interference (PROMIS) from baseline to pre-cycle 2 (calculated as the score pre-cycle 2 minus the score at baseline). Positive values indicate increasing pain.

    Higher scores indicate worse pain The statistical test assesses if there is a significant change in pain interference from baseline to pre-cycle 2

    Wilcoxon signed-rank test

    T-scores are standardized to the general population with a mean of 50 and standard deviation of 10. Higher scores indicate worse anxiety symptoms. A T-score of 55-60 indicates mild pain interference, 60-70 indicates moderate pain interference, and 70-80 indicates severe pain interference.

    Measured: Up to 6 months

  4. Assess the Impact on Pain Severity

    Change in Pain Intensity, as assessed on the numerical rating scale 11, from baseline to pre-cycle 2 (calculated as the score pre-cycle 2 minus the score at baseline). Positive values indicate increasing pain.

    Higher scores indicate worse pain The statistical test assesses if there is a significant change in pain intensity from baseline to pre-cycle 2 Wilcoxon signed-rank test

    The Numerical Rating Scale-11 (NRS-11) is a self-report segmented 11-point numeric scale that assesses pain severity. It consists of a horizontal line with 0 representing "no pain" at the right end of the line and 10 representing "worst pain you can imagine" at the left end.

    Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Feb 2018
  2. Study start2 Oct 2019
  3. Primary completion22 Jun 2022
  4. Study completion1 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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 MPNST
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03433183
Sponsor's protocol ID
SARC031
Other IDs
CDMRP-NF150092
Status last verified
Apr 2026
First submitted
29 Jan 2018
Last updated
27 May 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Selumetinib and Sirolimus in people with Malignant Peripheral Nerve Sheath Tumors and Neurofibromatosis 1, run by Sarcoma Alliance for Research through Collaboration at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Benefit Rate of Selumetinib in Combination With Sirolimus in Patients With Unresectable or Metastatic NF1 Associated or Sporadic MPNST. (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03433183.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.

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