Selumetinib + Sirolimus for Peripheral Nerve Sheath Tumor

No longer recruiting at 6 trial locations

Overseen By SARC Office

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Sarcoma Alliance for Research through Collaboration

Must not be taking: Corticosteroids, Immunosuppressants, Vitamin E, others

Disqualifiers: Uncontrolled hypertension, Diabetes, Cardiac, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs, selumetinib (a targeted therapy) and sirolimus (an immunosuppressant), to determine their effectiveness for people with malignant peripheral nerve sheath tumors (MPNST) linked to neurofibromatosis type 1 or occurring sporadically. These tumors cannot be surgically removed or have spread to other parts of the body. The trial aims to assess whether this treatment can improve the condition of patients who have already tried other chemotherapy treatments. Individuals with these tumors, whose cancer has progressed despite other treatments, might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that selumetinib and sirolimus have been studied for safety when used together. Previous studies have indicated that the combination produces side effects similar to other treatments. Selumetinib may cause side effects such as skin rash, diarrhea, and tiredness. Sirolimus, often used for transplant patients, can lead to mouth sores, high blood pressure, and increased cholesterol.

In a study on the combination of selumetinib and sirolimus, researchers examined any new or serious side effects. While side effects can occur, they are usually manageable. Both drugs are taken orally, which is generally more comfortable for patients than injections.

Although these treatments have shown some side effects, ongoing research aims to better understand their safety and effectiveness when used together. This is an important step to ensure they provide more benefits than risks for patients with certain types of cancers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of selumetinib and sirolimus for treating Malignant Peripheral Nerve Sheath Tumors (MPNSTs) because it targets cancer cells differently than current options. Most treatments for MPNSTs, like chemotherapy and radiation, aim to kill rapidly dividing cells, but this combo goes further by blocking specific pathways that tumors rely on to grow. Selumetinib is a MEK inhibitor, which disrupts a key signal in cancer cell proliferation, while sirolimus is an mTOR inhibitor, which stops cancer cells from getting the nutrients they need to thrive. This dual-target approach could provide a one-two punch against tumors, offering hope for patients with this challenging cancer.

What evidence suggests that this treatment might be an effective treatment for MPNST?

This trial will evaluate the combination of selumetinib and sirolimus for treating malignant peripheral nerve sheath tumors (MPNST) that cannot be surgically removed or have spread. Research has shown that selumetinib, when combined with sirolimus, may help treat certain nerve tumors. Studies have found that selumetinib can shrink tumors and improve symptoms in people with neurofibromatosis type 1 (NF1). Selumetinib blocks a pathway that aids tumor growth, while sirolimus blocks another pathway involved in cell growth and survival. Together, these drugs might effectively manage MPNST. ^{1 5 6 7 8}

Who Is on the Research Team?

Brigitte Widemann, MD

Principal Investigator

National Cancer Institute (NCI)

AeRang Kim, MD, PhD

Principal Investigator

Children's National Research Institute

Are You a Good Fit for This Trial?

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Selumetinib
• Sirolimus

How Is the Trial Designed?

Group I: Selumetinib and Sirolimus Experimental Treatment 2 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)

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03433183

SARC031: MEK Inhibitor Selumetinib (AZD6244) in ... Clinical benefit rate of selumetinib in combination with sirolimus in patients with unresectable or metastatic NF1 associated or sporadic MPNST. An ...

2. researchgate.net researchgate.net/publication/327457242_SPRINT_Phase_II_study_of_the_MEK_12_inhibitor_selumetinib_AZD6244_ARRY-142886_in_children_with_neurofibromatosis_type_1_NF1_and_inoperable_plexiform_neurofibromas_PN

SPRINT: Phase II study of the MEK 1/2 inhibitor selumetinib ... MEK inhibition with selumetinib has demonstrated the ability to reduce tumor volume and improve symptoms in the majority of patients with NF1- ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9893996/

Sporadic Metastatic Malignant Peripheral Nerve Sheath ... Here we present a case of a patient diagnosed with sporadic MPNST with an identified NF1 gene treated successfully with trametinib.

4. dana-farber.org dana-farber.org/clinical-trials/19-445

A Phase 2 Trial of the MEK inhibitor selumetinib (AZD6244 ... To determine the clinical benefit rate of selumetinib in combination with sirolimus in patients with unresectable or metastatic neurofibromatosis type 1 ...

5. sarctrials.org sarctrials.org/clinical-trials/sarc031/

SARC031 MPNST Sarcoma Clinical Trial - SARC trials Unresectable or Metastatic NF1 Associated or Sporadic Malignant Peripheral Nerve Sheath Tumors (MPNST) DRUG: Selumetinib in Combination with Sirolimus.

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03433183/

Clinical Trial: NCT03433183 Clinical benefit rate of selumetinib in combination with sirolimus in patients with unresectable or metastatic NF1 associated or sporadic MPNST.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf

213756Orig1s000 - accessdata.fda.gov The. SPRINT trial evaluated selumetinib ... The primary safety risks of selumetinib are consistent with the profiles of other approved MEK.

8. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=19-C-0061&&query=Type%20Neuroendocrine%20Tumor

Protocol Details The drugs, selumetinib and vistusertib, both affect tumor growth. Objective: To study the effects of selumetinib plus sirolimus on people with NF1 and MPNST.