Primary Objective To demonstrate objective responses using MRI or CT, positron emission
tomography - computerized tomography (PET-CT) and/or PET-MRI imaging. The same CT or MRI
imaging to assess disease burden at study entry will be compared at week 6 and 3 months.
Patients without progression at 3 months will continue treatment and have imaging at 6, 9
and 12 months after study entry. Metabolic response will be compared with study entry PET-CT
or PET-MRI and scans at 6 weeks, 3 months and 12 months.
Secondary Objectives Progression - free Survival: This will be calculated according to
Response Evaluation Criteria In Solid Tumors (RECIST) or Response Assessment in
Neuro-Oncology (RANO) and /or development of new disease
Overall survival: Overall survival will be determined by email or telephone contact.
PG-PG (only): to determine efficacy of ONC201 by reduction in dose of anti-hypertensive
medications.
Study Design: Phase 2 open-label fixed dose study Metastatic neuroendocrine tumors including
PC-PG are rare diseases. This study design has been chosen to see whether ONC201 is
associated with reduction of anti-hypertension medications, safety and significant efficacy
against neuroendocrine tumors, especially PC-PG.
The recommended phase II dose as flat every 3 week dosing of 625mg orally every 3 weeks will
be used. The same imaging at study entry will be used at subsequent time points (CT or MRI
for week 6 and 3, 6, 9, and 12 months; PET-CT or PET-MRI will be at 6 weeks 3 months and 12
months. Imaging modality choice will be influenced by the quality of prior scans of the
subject and will be ordered so clinical comparison is possible.
Inclusion Criteria:
- Subjects must have recurrent or metastatic neuroendocrine tumor including A) Cohort A
. Pheochromocytoma-paraganglioma (PC-PG). N=12. B) Cohort B. Other neuroendocrine
cancer varieties as characterized by expression of neuroendocrine markers on tumor
tissue including cluster of differentiation 56 (CD56), synaptophysin,
bombesin/gastrin-releasing peptide receptor, chromogranin and/or presence of a
detectable serum or urine biomarker (3-methoxytyramine, normetanephrine,
metanephrines, homovanillic acid (HVA), vanillylmandelic acid (VMA), dopamine, or
bombesin/pro-gastrin releasing peptide). Varieties may include neuroblastoma, Ewing
sarcoma, neuroectodermal tumor, primitive neuroectodermal tumor (PNET), desmoplastic
small round cell tumor, and small cell carcinoma, N=12
- There is no limit on number of prior therapies.
- Subjects must have normal organ and marrow function as defined below. Studies should
be done within 3 weeks prior to enrollment
- 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) (SGOT) ≤ 5 X institutional upper limit of
normal
- Alanine aminotransferase (ALT) (SGPT) ≤ 5 X institutional upper limit of normal
- Serum Creatinine <3.0mg/dL
- ≥ 1 lesion detectable on CT, MRI, 18FDG PET-CT, or PET-MRI
- Subjects must have the ability to understand and the willingness to sign a written
informed consent document
- Performance status: 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 metaclopromide, chlorpromazine, prochlorperazine, droperidol,
ephedrine, pseudoephedrine, fenfluramine, methylphenidate, phentermine,
amitryptiline, imipramine, tranylcypromine, moclobemide, phenelzine, paroxetine, 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>100mmHg) 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
