Phase I Trial of TURALIO(R) (Pexidartinib, PLX3397) in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN) and Tenosynovial Giant Cell Tumor ...

Sarcoma Clinical Trial

Official title: Phase I Trial of TURALIO (Pexidartinib, PLX3397) in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN) and Tenosynovial Giant Cell Tumor (TGCT)

Status Recruiting

Clinical Trial Summary

Background:

• Some people with cancer have solid tumors. Others have refractory leukemia. This may not go away after treatment. Researchers want to see if a drug called TURALIO(R) can shrink tumors or stop them from growing.

Objectives:

• To find the highest safe dose and side effects of TURALIO(R). To see if it helps treat certain types of cancer.

Eligibility:

• People ages 3-35 with a solid tumor or leukemia that has returned or not responded to cancer therapies.

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 TURALIO(R) 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 leukemia will have blood tests. They may have a bone marrow sample taken.

• Some participants may have a biopsy.

• When finished taking TURALIO(R), participants will have follow-up visits. They will repeat the screening tests and note side effects.

Clinical Trial Description

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).

• TURALIO(R) 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

-Evaluate the safety and tolerability of TURALIO(R) and determine a recommended phase II dose of TURALIO(R) 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).

Eligibility

->= 3 and <= 35 years of age

• Recurrent or refractory solid tumors including primary neoplasms of the central nervous system and patients with NF1 and MPNST, or refractory leukemias (AML or ALL).

• 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.

Design

• Using a rolling-six phase I design with 2-6 subjects per dose level and standard definitions of MTD (during cycle 1) and DLT.

• TURALIO(R) will be administered orally (125 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 TURALIO(R) 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. ;

Related Conditions & MeSH terms

• Giant Cell Tumor of Tendon Sheath
• Giant Cell Tumors
• Leukemia
• Leukemia, Promyelocytic, Acute
• Neurofibroma
• Neurofibroma, Plexiform
• Neurofibromatoses
• Neurofibromatosis 1
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Sarcoma

• NCT number: NCT02390752
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Elaine W Thomas
• Phone: (240) 858-7013
• Email: elaine.thomas@nih.gov
• Status: Recruiting
• Phase: Phase 1
• Start date: April 29, 2015
• Completion date: December 1, 2025