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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: 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 Maligna

Brief 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.

Detailed Summary: 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.
Sponsor: Gary Schwartz

Current Primary Outcome: Maximum tolerated dose (MTD, in milligrams) of PLX3397 in combination with Sirolimus [ Time Frame: Up to 3 years ]

For the Phase 1 cohort, the dose combination associated with a target probability of dose limiting toxicity of 0.25. The MTD will be estimated using the time to event continual reassessment method (TITE-CRM).


Original Primary Outcome:

  • Progression free survival (PFS) rate [ Time Frame: Up to 3 years ]
    For the Phase 2 cohort, PFS is defined as the time from the start of treatment until disease progression or death from any cause
  • Maximum tolerated dose (MTD, in milligrams) of PLX3397 in combination with Sirolimus [ Time Frame: Up to 3 years ]
    For the Phase 1 cohort, the dose combination associated with a target probability of dose limiting toxicity of 0.25. The MTD will be estimated using the time to event continual reassessment method (TITE-CRM).


Current Secondary Outcome:

  • Overall survival rate [ Time Frame: Up to 3 years ]
    The time from the start of treatment until death, estimated using the Kaplan Meier method.
  • Progression free survival (PFS) rate [ Time Frame: Up to 3 years ]
    For the Phase 2 cohort, PFS is defined as the time from the start of treatment until disease progression or death from any cause.


Original Secondary Outcome: Overall survival rate [ Time Frame: Up to 3 years ]

The time from the start of treatment until death, estimated using the Kaplan Meier method.


Information By: Columbia University

Dates:
Date Received: October 21, 2015
Date Started: October 2014
Date Completion: October 2017
Last Updated: January 9, 2017
Last Verified: January 2017