SARC031: MEK Inhibitor Selumetinib (AZD6244) in Combination With the mTOR Inhibitor Sirolimus for Patients With Malignant Peripheral Nerve Sheath Tumors
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|ClinicalTrials.gov Identifier: NCT03433183|
Recruitment Status : Not yet recruiting
First Posted : February 14, 2018
Last Update Posted : July 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|Malignant Peripheral Nerve Sheath Tumors Neurofibromatosis 1||Drug: Selumetinib Drug: Sirolimus||Phase 2|
I. 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Intervention 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)|
|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|
|Estimated Study Start Date :||October 2018|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||September 2021|
Experimental: Selumetinib and Sirolimus
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 (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.
Other Name: AZD6244
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.
Other Name: Rapamycin
- 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 ]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.
- Progression free and overall survival [ Time Frame: Progression-Free Survival (PFS) is defined as the duration of time from the start of treatment to the time of objective progression or death. [Time Frame: Up to 4 years] ]Determined using the Kaplan-Meier method with PFS at important time points reported along with 95% two sided confidence intervals.
- Define and describe the toxicities of selumetinib in combination with sirolimus in patients with unresectable or metastatic NF1 associated or sporadic MPNST. [ Time Frame: Up to 6 months ]This study will use CTEP Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 for toxicity and adverse event reporting. The toxicities will be graded and summarized descriptively and tabulations on the type, severity and relationship to study treatment will be performed.
- Assess the impact on pain interference [ Time Frame: Up to 6 months ]Pain interference metrics will be assessed using the Patient Reported Outcomes Measurements Information System (PROMIS) scale to assess the impact of pain on daily activities. This is a self-report measure that assesses the degree to which pain has interfered with the ability to complete daily activities over the past 7 days. Items are rated on a 5-point Likert scale and the measures yield standardized T-scores.
- Assess the impact on pain severity [ Time Frame: Up to 6 months ]Pain metrics will be assessed using the Numerical Rating Scale-11 (NRS-11) scale to assess pain severity. The scale consists of a horizontal line with 0 representing "no pain" and 10 representing "worst pain you can imagine." Patients will circle one number from 0 to 10 that best describes how much their tumor pain hurt during the past week.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03433183
|Contact: SARC Office||(734) firstname.lastname@example.org|
|Principal Investigator:||AeRang Kim, MD, PhD||Children's Research Institute|
|Principal Investigator:||Brigitte Widemann, MD||National Cancer Institute (NCI)|