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 ...
\- 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:
* Individuals will be screened with:
* Medical history
* Physical exam
* Blood and urine tests
* Heart tests
* Scans or other tests of the tumor
* Individuals 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. Individuals will keep a diary of symptoms.
* Individuals with solid tumors will have scans or x-rays.
* Individuals with leukemia will have blood tests. They may have a bone marrow sample taken.
* Some individuals may have a biopsy.
* When finished taking TURALIO(R), individuals will have follow-up visits. They will repeat the screening tests and note side effects.
Eligibility criteria
Qualifiers
Individuals must have recurrent or refractory solid tumors or acute leukemia (limited to AML or ALL) or have been intolerant of prior therapies, confirmed by the Laboratory of Pathology, NCI, e.g., solid tumors including rhabdomyosarcoma, Ewing sarcoma, soft tissue sarcomas. These may include primary neoplasms of the central nervous system, such as high-grade (WHO grade III-IV) glioma. Individuals with diffuse intrinsic pontine glioma (DIPG) or optic pathway glioma are exempt from histologic verification. For DIPG typical MRI findings must be present which include hypo- or isointense on T1-weighted imaging, hyperintense on FLAIR or T2-weighted imaging, epicenter in the pons in the face of a typical clinical presentation. Optic pathway gliomas are located in the optic pathway and are typically hypo- or iso-intense on T1 and hyperintense on T2-weighted images.
In addition, individuals with NF1 and with malignant peripheral nerve sheath tumor (MPNST).
Individuals must have relapsed after or be refractory to effective standard therapies. There are no limits on number of prior therapeutic regimens.
Disease status: Individuals with refractory solid tumors including patients with NF1 and MPNST must have evaluable disease, patients with leukemia must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry.
Disqualifiers
Individuals who are pregnant or breast feeding or who become pregnant while enrolled on this trial will be excluded from participation, due to the unknown effects of TURALIO(R) on a growing fetus or newborn child.
Ongoing treatment with any other cancer therapy or investigational agent, with the exception of IT chemotherapy for leukemia, when indicated.
Individuals who require therapy with warfarin.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.