Last updated on July 2020

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

Brief description of study

  • 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.
  • To find the highest safe dose and side effects of PLX3397. To see if it helps treat certain types of cancer.
  • 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.
  • 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 will have blood tests. They may have a bone marrow sample taken.
  • Some participants may have a biopsy.
  • When finished taking PLX3397, participants will have follow-up visits. They will repeat the screening tests and note side effects.
  • Phase II will follow the same procedures as Phase I above, but participants will also fill out questionnaires about their pain and quality of life.

Detailed Study Description


  • 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 analysis).


  • Tumor type:
  • Phase I: Children (greater than or equal to 3 and lessthan or equal to 21 years of age) with recurrent or refractory solid tumors including primary neoplasms of the central nervous system and patients with NF1 and MPNST, or Children (greater than or equal to 3 and less than or equal to 21 years of age) with refractory leukemias (AML or ALL) (Phase 1).
  • Phase II: Patients with NF1 and inoperable PN, that cause morbidity (greater than or equal to 3 and less than or equal to 35 years of age).
  • Subjects must have adequate performance status, be able to swallow tablets, may not be pregnant or breastfeeding, and have adequate major organ function. Subjects with history of severe or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic cardiovascular or pulmonary disease, or history of prolonged QT syndrome will be excluded.


  • Phase I
  • Using a rolling-six phase I design with 2-6 subjects per dose level and standard definitions of MTD (during cycle 1) and DLT.
  • PLX3397 will be administered orally (200 mg capsules) once daily on a continuous basis for cycles of 28 days without a rest period between cycles. Patients must be able to swallow intact capsules. Dosing will be based on body surface area (BSA), and the total weekly dose will be rounded to within 10% of calculated dose using a dosing nomogram.
  • At the MTD, the recommended phase II dose level will be expanded to up to 12 patients with attempts made to enroll at least 3 patients with refractory solid tumors and 3 patients with refractory acute leukemia (ALL and AML) to gain more experience with the toxicities and pharmacokinetics of PLX3397 in these disease cohorts. Attempts will be made to enroll equal numbers of patients between the ages of 3 and 12 years and over 12 years of age to gain pharmacokinetic and safety data over a broad age range.
  • Phase II
  • A Simon 2-stage design will be used: 9 evaluable patients with NF1 and inoperable PN that cause morbidity will be enrolled on the initial stage, and if greater than or equal to 1/9 patients have a response (PN volume decrease greater than or equal to 20% compared to baseline), enrollment will be expanded to a total of 17 evaluable patients.
  • Impact of therapy on patient-reported outcomes will be evaluated in patients with PN. This study will assess both general health-related qualify of life (QOL) and pain (pain intensity and pain interference) as patient-reported outcomes (PROs).
  • To complete both Phase I and Phase II portions, a maximum of (24 + 17= 41 plus up to 6 to replace inevaluable patients) 47 patients will be accrued in 2 to 2.5 years.

Clinical Study Identifier: NCT02390752

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Recruitment Status: Open

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