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

Inclusion Criteria

• Subjects must have unresectable, recurrent, locally advanced, or metastatic neuroendocrine tumor including * Cohort A; unresectable, recurrent, locally advanced, or metastatic pheochromocytoma-paraganglioma (PC-PG) who have failed or are refractory to available therapies; sample size (N)=12 * Cohort B will include only patients with unresectable, locally advanced or metastatic tumors who have failed or are refractory to available therapy; other neuroendocrine cancer varieties as characterized by expression of neuroendocrine markers on tumor tissue including CD56, synaptophysin, chromogranin and/or presence of a detectable serum or urine biomarker (3-methoxytyramine, normetanepherine, metanepherines, homovanillic acid [HVA], vanillylmandelic acid [VMA], and dopamine), varieties will include neuroblastoma, Ewing sarcoma, neuroectodermal tumor, clear call sarcoma, myoepithelial tumor, primitive neuroectodermal tumor [PNET], desmoplastic small round cell tumor, round cell sarcoma, and unresectable, metastatic or locally advanced , well-differentiated neuroendocrine tumors who have relapsed or are refractory to at least 2 systemic therapies (e.g. lanreotide, sunitinib, or everlimus); patients with small cell carcinomas will not be included in this clinical trial; N=12
• There is no limit on number of prior therapies
• Hemoglobin >= 10.0 g/dl
• Leukocytes >= 1500/mcL
• Absolute neutrophil count >= 1,000/mcL
• Platelet count >= 75000/mcL
• Total bilirubin within 1.5 x normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 5 X institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 X institutional upper limit of normal
• Serum creatinine < 3.0 mg/dL
• >= 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 performance status >= 60%

Exclusion Criteria

• Subjects not able to take oral drugs
• Subjects receiving any other investigational agents
• Subjects receiving cytotoxic chemotherapy
• Patients who occasionally or regularly use medications that impact dopamine receptor signaling and can cause side effects in people with neuroendocrine tumors including PC-PG such as metoclopromide, chloropromazine, prochlorperazine, droperidol, ephedrine, pseudoephedrine, fenfluramine, methylphenidate, phentermine, amitryptaline, imipramine, tranciproamine, moclobemide, phenelzine, paroexetine, and fluoxetine
• 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

PRIMARY OBJECTIVES:

I. To demonstrate objective responses using magnetic resonance imaging (MRI) or computed tomography (CT), positron emission tomography (PET)-CT and/or PET-MRI imaging.

SECONDARY OBJECTIVES:

I. Progression – free survival.

II. Overall survival.

III. To determine efficacy of akt/ERK inhibitor ONC201 (ONC201) by reduction in dose of anti-hypertensive medications (pheochromocytoma-paraganglioma [PC-PG] only).

TERTIARY OBJECTIVES:

I. To determine time course of ONC201 efficacy - by measurement of pharmacodynamics (PD) and relevant blood biomarkers such as prolactin, normetanepherine, metanepherines, chromogranin A, and/or bombesin.

OUTLINE:

Patients receive akt/ERK inhibitor ONC201 orally (PO) weekly. Courses repeat every week for up to 1 year 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 2 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
• Clinicaltrials.gov ID NCT03034200