Clinical Trial: PLX3397 in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN)

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

Official Title: Phase I/II Trial of PLX3397 in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neuro

Brief Summary:

Background:

- Some people with cancer have solid tumors. Others have refractory leukemia. This doesn t go away after treatment. Researchers want to see if a drug called PLX3397 can shrink tumors or stop them from growing.

Objectives:

- To find the highest safe dose and side effects of PLX3397. To see if it helps treat certain types of cancer.

Eligibility:

  • People ages 3 22 with a solid tumor or leukemia that has returned or not responded to cancer therapies.
  • For Phase II, people ages 3 31 with a Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibroma (PN) that cannot be removed with surgery.

Design:

  • Participants will be screened with:
  • Medical history
  • Physical exam
  • Blood and urine tests
  • Heart tests
  • Scans or other tests of the tumor
  • Participants will take PLX3397 as a capsule once daily for a 28-day cycle. They can do this for up to 2 years.
  • During the study, participants will have many tests and procedures. They include repeats of the screening tests. Participants will keep a diary of symptoms.
  • Participants with solid tumors will have scans or x-rays.
  • Participants with NF1 PN will have MRI scans.
  • Participants with leukemia

    Detailed Summary:

    Background

    • Traditional therapeutic approaches to pediatric cancer have focused on cytotoxic agents and, more recently, targeted inhibition of cellular signaling pathways through the use of small molecule kinase inhibitors. Despite these interventions, significant numbers of pediatric cancer patients develop recurrent and resistant disease. Targeting the tumor microenvironment is a promising but incompletely explored strategy for the treatment of pediatric cancer and non-cancer tumors.
    • This trial will begin to explore the disruption of the interaction between neoplastic cells and the myeloid component of the tumor microenvironment as a treatment strategy for pediatric cancers and neurofibromatosis type 1 (NF1) related plexiform neurofibromas (PN) and malignant peripheral nerve sheath tumor (MPNST).
    • PLX3397 is an orally available small molecule inhibitor of class III protein tyrosine kinases including Kit, CSF1R (colony stimulating factor 1 receptor)/Fms (Feline McDonough Sarcoma), and oncogenic Flt3 (Fms like tyrosine kinase).

    Primary Objectives

    • Phase I: Evaluate the safety and tolerability of PLX3397, and determine a recommended phase II dose of PLX3397 in pediatric patients with refractory solid tumors including NF1 MPNST and brain tumors or refractory leukemias, limited to acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL).
    • Phase II: Determine the anti-tumor activity of PLX3397 in patients with NF1 PN. Objective response rate (ORR) will be defined as the proportion of patients with a partial response (PN volume decrease greater than or equal to 20% determined by volumetric MRI a
      Sponsor: National Cancer Institute (NCI)

      Current Primary Outcome:

      • Phase I: determine a phase II dose of PLX3397 [ Time Frame: First cycle ]
      • Phase II: determine antitumor activity of PLX3397 in patients with NF1 PN [ Time Frame: At each response evaluation ]


      Original Primary Outcome: Same as current

      Current Secondary Outcome:

      • To study PK [ Time Frame: Cycles 1 and 2 ]
      • Determine effect of PLX 3397 on circulating [ Time Frame: Before C1 and then C1D7 and then at each restaging evaluationevaluationbiomarkers ]
      • Evaluate biologic activity and extended tolerability of PLX3397 [ Time Frame: Each cycle ]
      • Evaluated patient reported and functional outcomes [ Time Frame: Prior to cycles 3,5,9,13 and every 6 cycles ]


      Original Secondary Outcome: Same as current

      Information By: National Institutes of Health Clinical Center (CC)

      Dates:
      Date Received: March 17, 2015
      Date Started: March 6, 2015
      Date Completion: December 1, 2018
      Last Updated: May 12, 2017
      Last Verified: March 3, 2017