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Akt / ERK Inhibitor ONC201 in Treating Patients with Neuroendocrine Tumors That Are Locally Advanced, Metastatic, Recurrent, Refractory, or Cannot Be Removed by Surgery

Trial Status: Closed to Accrual

This phase II trial studies how well akt / ERK inhibitor ONC201 works in treating patients with neuroendocrine tumors that have spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic), have come back (recurrent), do not respond to treatment (refractory), or cannot be removed by surgery (unresctable). Akt / ERK inhibitor ONC201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Inclusion Criteria

  • 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%

Exclusion Criteria

  • 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


Case Comprehensive Cancer Center
Contact: Peter Meade Anderson
Phone: 216-445-4007


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

Lead Organization
Case Comprehensive Cancer Center

Principal Investigator
Peter Meade Anderson

  • Primary ID CASE2716
  • Secondary IDs NCI-2017-01645
  • ID NCT03034200