Oral ONC201 in Treating Patients With Advanced Solid Tumors

NCT02250781 | Completed Phase 1

• 3 other identifiers: 051403NCI-2014-01305P30CA072720
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity rate during cycle 1 of treatment with oral ONC201

  Day 21

Secondary Outcomes (6)

• Recommended phase II dose (RP2D) for oral ONC201

  At the end of 6 weeks therapy

• Frequency of toxicities associated with ONC201

  Up to 4 weeks after end of study treatment

• Pharmacokinetics of oral ONC201 - Half-life

  Up to 4 weeks of therapy

• Pharmacokinetics of oral ONC201 - Maximum concentration

  Up to 4 weeks of therapy

• Pharmacokinetics of oral ONC201 - Area under the curve (AUC) over time

  Up to 4 weeks of therapy

Study Arms (1)

Treatment (Oral ONC201)

EXPERIMENTAL

Patients receive Oral ONC201 PO on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Oral ONC201

Interventions

Oral ONC201 DRUG

Given PO

Also known as: ONC201, TIC10

Treatment (Oral ONC201)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Cancer Institute (NCI): collaborator
• Rutgers Cancer Institute of New Jersey: collaborator

Study Sites (1)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Related Publications (1)

• Stein MN, Malhotra J, Tarapore RS, Malhotra U, Silk AW, Chan N, Rodriguez L, Aisner J, Aiken RD, Mayer T, Haffty BG, Newman JH, Aspromonte SM, Bommareddy PK, Estupinian R, Chesson CB, Sadimin ET, Li S, Medina DJ, Saunders T, Frankel M, Kareddula A, Damare S, Wesolowsky E, Gabel C, El-Deiry WS, Prabhu VV, Allen JE, Stogniew M, Oster W, Bertino JR, Libutti SK, Mehnert JM, Zloza A. Safety and enhanced immunostimulatory activity of the DRD2 antagonist ONC201 in advanced solid tumor patients with weekly oral administration. J Immunother Cancer. 2019 May 22;7(1):136. doi: 10.1186/s40425-019-0599-8.

  PMID: 31118108 DERIVED

MeSH Terms

Interventions

TIC10 compound

Study Officials

• Jyoti Malhotra

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2014
• First Posted: September 26, 2014
• Study Start: January 12, 2015
• Primary Completion: October 18, 2018
• Study Completion: October 25, 2018
• Last Updated: May 22, 2019

Record last verified: 2019-05

Locations

US (1)