Overview

Oral ONC201 in Treating Patients With Advanced Solid Tumors

Status:
Completed
Trial end date:
2018-10-25
Target enrollment:
0
Participant gender:
All
Summary
This phase I trial studies the side effects and best dose of Oral ONC201 in treating patients with advanced solid tumors. Oral ONC201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Rutgers, The State University of New Jersey
Collaborators:
National Cancer Institute (NCI)
Rutgers Cancer Institute of New Jersey
Treatments:
TIC10 compound
Criteria
Inclusion Criteria:

- Patients with an advanced solid tumor that is refractory to standard treatment, or for
which no standard therapy is available, or the subject refuses standard therapy

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1

- All patients must have measurable or evaluable disease defined by Response Evaluation
Criteria In Solid Tumors (RECIST) 1.1 criteria; if the patient has received prior
radiation therapy one measurable lesion must be outside the irradiated field; lesions
within an irradiated field will be followed as non-target lesions and considered
evaluable; if the only site of measurable disease is within a previously irradiated
field then 6 months must have elapsed between the completion of radiation therapy and
entry on study to be considered measurable

- Patients are eligible for enrollment if they have not had prior investigational or
approved cytotoxic chemotherapy within 28 days prior to the first dose (week 1, day
1); 42 days in the case of alkylating agents; 28 days or 5 half-lives (whichever is
less; but not less than 14 days) in case of investigational or approved molecularly
targeted agent; 14 days in the case of radiotherapy; any number of prior therapies is
allowable

- All adverse events grade =< 2 related to prior therapies (chemotherapy, radiotherapy,
and/or surgery) must be resolved, except for alopecia or neuropathy; patients are
eligible for enrollment if they have had no surgery in the prior 6 weeks (minor
surgical procedures such as skin biopsies and port placement done on an outpatient
basis do not require a waiting period)

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Hemoglobin >= 9.0 mg/dL without transfusion in 2 prior weeks

- Total bilirubin within normal range; for patients with liver metastases, serum
bilirubin =< 1.5 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate transaminase [SGPT]) =< 2.5 x
upper limit of normal

- Measured OR estimated creatinine clearance >= 40 mL/min/1.73 m^2 for patients with
creatinine levels above normal

- Men or women treated or enrolled on this protocol must agree to use double barrier
contraceptives; oral, implantable, or injectable contraceptives are not considered
effective for this study; women of child-bearing potential must have a negative serum
pregnancy test =< 72 hours prior to initiating treatment; subjects must agree to use
double barrier contraceptive therapy for the duration of study participation, and 4
months after completion of ONC201 administration; should a woman become pregnant or
suspect she is pregnant while she or her partner is participating in this study, she
should inform her treating physician immediately

- Tumor specimen (paraffin-embedded block or frozen tissue) from prior resection or
biopsy available that is sufficient to perform pharmacodynamic assays (>= 3 slides for
immunohistochemistry [IHC]) - mandatory for patients in the dose expansion cohort only

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients with symptomatic brain metastases are excluded; however, patients with
asymptomatic central nervous system (CNS) metastases may participate in this trial;
the patient must have completed any prior local treatment for CNS metastases > 28 days
prior to study entry including radiotherapy or surgery; patients receiving steroids
for CNS metastases may not participate on this study

- Prior bevacizumab for treatment of glioblastoma or high grade glioma

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ONC201 or its excipients

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
study requirements

- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator

- Patients with a known human immunodeficiency virus (HIV)-positive test on combination
antiretroviral therapy are ineligible for the initial first-in-man trial

- Patient has active cardiac disease including any of the following:

- Corrected QT (QTc) > 500 msec on screening electrocardiogram (ECG) (using the QTc
Fridericia [F] formula)

- Angina pectoris that requires the use of anti-anginal medication

- Ventricular arrhythmias except for benign premature ventricular contractions

- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication

- Conduction abnormality requiring a pacemaker

- Valvular disease with document compromise in cardiac function

- Symptomatic pericarditis

- Patient has a history of cardiac dysfunction including any of the following:

- Myocardial infraction within the last 6 months, documented by persistent elevated
cardiac enzymes or persistent regional wall abnormalities on assessment of left
ventricular ejection fraction (LVEF) function

- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)

- Documented cardiomyopathy

- Patient with stroke in the last 3 months

- Patients with a history of seizures with in the past 3 months

- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of ONC201 (uncontrolled nausea, vomiting, diarrhea, malabsorption
syndrome, or small bowel resection)

- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (e.g., filgrastim [G-CSF], granulocyte-macrophage colony-stimulating factor
[GM-CSF]) =< 2 weeks prior to starting study drug; erythropoietin or darbepoetin
therapy, if initiated at least 2 weeks prior to enrollment, may be continued

- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control; double barrier contraceptives must be
used through the trial by both sexes; oral, implantable, or injectable contraceptives
are not considered effective for this study

- Women of child-bearing potential must have a negative serum pregnancy test =< 72 hours
prior to initiating treatment

- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, must use highly effective contraception during treatment and for 16
additional weeks after stopping treatment; the highly effective contraception is
defined as either:

- True abstinence: when this is in line with the preferred and usual lifestyle of
the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception

- Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy
alone, only when the reproductive status of the woman has been confirmed by
follow up hormone level assessment

- Male partner sterilization (with the appropriate post-vasectomy documentation of
the absence of sperm in the ejaculate); for female subjects on the study, the
vasectomized male partner should be the sole partner for that patient

- Use of a combination of any two of the following (a+b):

1. Placement of an intrauterine device (IUD) or intrauterine system (IUS)

2. Barrier methods of contraception: condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
suppository

- Oral contraception, injected or implanted hormonal methods are not allowed

- Fertile males, defined as all males physiologically capable of conceiving
offspring must use condom during treatment and for an additional 16 weeks after
stopping treatment

- Female partner of male study subject should use highly effective contraception
during dosing of any study agent and for 16 weeks after final dose of study
therapy