Akt / ERK Inhibitor ONC201 in Treating Patients with Neuroendocrine Tumors That Are Locally Advanced, Metastatic, Recurrent, Refractory, or Cannot Be Removed by Surgery
- Subjects must have a unresectable, recurrent, locally advanced, refractory, or metastatic neuroendocrine tumor including pheochromocytoma-paraganglioma (PC-PG), desmoplastic small round cell tumor (DSRCT), Ewing sarcoma or primitive neuroectodermal tumor (PNET), or any neuroendocrine tumor with a catecholamine or dopamine biomarker or autocrine or paracrine dependence on dopamine including cholangiocarcinoma and adrenal cortical carcinoma (ACC). N=12
- There is no limit on number of prior therapies
- Hemoglobin >= 10.0 g/dl (within 3 weeks prior to enrollment)
- Leukocytes >= 1500/mcL (within 3 weeks prior to enrollment)
- Absolute neutrophil count >= 1,000/mcL (within 3 weeks prior to enrollment)
- Platelet count >= 75000/mcL (within 3 weeks prior to enrollment)
- Total bilirubin within 1.5 x normal institutional limits (within 3 weeks prior to enrollment)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 5 x institutional upper limit of normal (within 3 weeks prior to enrollment)
- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x institutional upper limit of normal (within 3 weeks prior to enrollment)
- Serum creatinine < 3.0 mg/dL (within 3 weeks prior to enrollment)
- >= 1 lesion detectable on CT, MRI, fludeoxyglucose F-18 (18FDG) PET-CT, or PET-MRI
- Subjects must have the ability to understand and the willingness to sign a written informed consent document
- Karnofsky or if < 16 years old Lansky Play performance status >= 60%
- Subjects not able to take oral drugs
- Subjects receiving any other investigational agents
- Subjects receiving cytotoxic chemotherapy
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, severe, uncontrolled hypertension (systolic > 150/diastolic > 100 mmHg) or other symptoms of catecholamine excess after efforts to achieve adequate alpha blockade then beta blockade
- Psychiatric illness/social situations that would limit compliance with study requirements including returning for scans, taking oral medication, home monitoring of blood pressure and heart rate, recording side effects in a self-report diary, or becoming pregnant while on study drug
- Pregnant and breast-feeding subjects
- Patients with prolactinomas
I. To demonstrate objective responses using magnetic resonance imaging (MRI) or computed tomography (CT), positron emission tomography (PET)-CT and/or PET-MRI imaging.
I. Progression – free survival.
II. Overall survival.
I. To determine time course of ONC201 efficacy by measurement clinically indicated blood biomarkers such as normetanepherine, metanepherines, and/or chromogranin A.
I. Plasma will be collected in BCT tubes, then frozen and stored for future studies of an exploratory nature.
Patients receive akt/ERK inhibitor ONC201 orally (PO) on days 1-2. Cycles repeat every week in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, and then yearly for up to 4 years.
Trial Phase Phase II
Trial Type Treatment
Case Comprehensive Cancer Center
Peter Meade Anderson
- Primary ID CASE2716
- Secondary IDs NCI-2017-01645
- Clinicaltrials.gov ID NCT03034200