NCT02584647

PLX3397 Plus Sirolimus in Unresectable Sarcoma and Malignant Peripheral Nerve Sheath Tumors

Phase I Study Evaluating Combination Therapy With the Receptor Tyrosine Kinase Inhibitor PLX3397 and Sirolimus in Patients With Unresectable Sarcoma and Phase II Study in Malignant Peripheral Nerve Sheath Tumors

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 39 (actual)
• Sponsor: Gulam Manji · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine if treatment with PLX3397 and Sirolimus will be tolerated and result in shrinking of the cancer or stopping the cancer from growing. In the phase I portion, the maximum tolerate dose of the study drug will be determined. In the Phase II portion, progression free survival will be assessed at the dose level found in Phase I. Participants will continue to take the study drug until they experience an unacceptable side effect or their disease progresses. Funding Source - FDA OOPD

Detailed description

Malignant peripheral nerve sheath tumors (MPNSTs) represent up to 10% of adult soft tissue sarcomas. Due to its rarity, few MPNST-specific prospective trials exist, and treatments are largely based on extrapolation from results from other sarcoma subtypes. Since the molecular pathways driving pathogenesis within sarcoma subtypes are distinct, these treatment options are likely suboptimal at best. Targeted therapies that block key pathways known to drive MPNST will likely result in superior tumor responses with limited toxicities.

Conditions

• Sarcoma
• Malignant Peripheral Nerve Sheath Tumors

Interventions

Type	Name	Description
DRUG	PLX3397	PLX3397 is a small molecule that potently and selectively inhibits macrophage colony-stimulating factor receptor (FMS), Kit, and FMS-like tyrosine kinase 3 (Flt3)-internal tandem duplication (ITD) kinases, which regulate key components of the tumor microenvironment and oncogenic variants of these kinases that drive certain tumors.
DRUG	sirolimus	Sirolimus is a macrocyclic lactone that binds to tacrolimus (FK506) binding protein 12 and inhibits mammalian target of rapamycin (mTOR) resulting in cell-cycle arrest and apoptosis. Sirolimus is currently approved as an immunosuppressive agent for organ transplantation and more recently, as a component of cardiac arterial stents because of its potent antiproliferative effects on fibroblasts responsible for restenosis after such a procedure (26) Sirolimus is commonly administered orally on a daily basis, in doses ranging from 2 to 40 mg/day.

Timeline

• Start date: 2015-11-04
• Primary completion: 2023-07-01
• Completion: 2024-10-01
• First posted: 2015-10-22
• Last updated: 2025-03-21
• Results posted: 2025-03-21

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study