Phase 2 Study of ONC201 in Neuroendocrine Tumors

November 4, 2024 updated by: Peter Anderson

The purpose of this study is to learn if a new drug, ONC201 can make tumors become smaller or go away completely. Investigators also want to learn if ONC201 can prevent new deposits of cancer from appearing in new places in participants (metastases). A phase 2 study of ONC201 in PC-PG (pheochromocytoma-paraganglioma) and other neuroendocrine tumors will determine whether inhibition of DRD2 (a member of the dopamine receptor family) is safe in unresectable, recurrent, locally advanced, refractory, or metastatic neuroendocrine cancers including PC-PG, desmoplastic small round cell tumor (DSRCT), Ewing sarcoma (PNET) or any other neuroendicrine tumor with a catecholamine or dopamine biomarker or autocrine or paracrine dependence on dopamine including cholangiocarcinoma and adrenal cortical carcinoma.

ONC201 is an investigational (experimental) agent and has a favorable safety profile in phase 1 and early phase 2 clinical trials in advanced cancers. 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Primary Objective To demonstrate objective responses using MRI or CT, and/or PET-CT 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 and/or biomarkers will be compared with study entry PET-CT 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 development of new disease

Overall survival: Overall survival will be determined by email or telephone contact.

Study Design: Phase 2 open-label fixed dose study Metastatic neuroendocrine tumors including PC-PG are rare diseases.

The current recommended phase II dose of 625 mg orally on 2 consecutive days every week 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) Imaging modality choice will be influenced by the quality of prior scans of the subject and will be ordered so clinical comparison is possible.

Because of travel and lodging considerations associated with the COVID-19 pandemic, some information by the study team/PI may be obtained using virtual visits and 2nd read of scans sent to Cleveland Clinic

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Pediatric and Taussig Cancer Institute, Case Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

  1. "Subjects must have a unresectable, recurrent, locally advanced, refractory, or metastatic neuroendocrine tumor including pheochromocytoma-paraganglioma (PC-PG), DSRCT, Ewing Sarcoma or 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).
  2. There is no limit on number of prior therapies.
  3. Age ≥14 years.

  4. 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
    • AST (SGOT) ≤ 5 X institutional upper limit of normal
    • ALT (SGPT) ≤ 5 X institutional upper limit of normal

    • Serum Creatinine <3.0mg/dL

      • 5 1 lesion detectable on CT, MRI, 18FDG PET-CT

6 Subjects must have the ability to understand and the willingness to sign a written informed consent document.

7: Karnofsky or if <16 years old Lansky Play Performance status ≥ 60%

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Metastatic PC-PG
625mg ONC201 will be given once weekly
Drug: ONC201
625mg ONC201 will be given on two consecutive days each week
Experimental: Arm B: Other NETs
625mg ONC201 will be given once weekly
Drug: ONC201
625mg ONC201 will be given on two consecutive days each week
Experimental: Arm C: PC-PG + other NETs
625mg ONC201 will be given on day 1 and day 2 of each week
Drug: ONC201
625mg ONC201 will be given on two consecutive days each week

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor Response According to RECIST Criteria
Time Frame: Up to 1 Year

Complete Response (CR) Disappearance or fibrosis of all target lesions. Any pathologic lymph nodes must have reduction in short axis to <10mm and standardized uptake value (SUV) is <4.

Partial Response (PR) At least 30% decrease in sum of longest diameters of target lesions (compared to initial on study baseline) and any decrease in SUV in Fludeoxyglucose 18F (18FDG) imaging Stable disease (SD) 0-29% decrease in sum of longest diameters of target lesions (compared to initial on study baseline) or 0-19% increase in sum of longest diameters of target lesions (compared to initial on study baseline). SUV may increase or decrease Progressive disease 20% or more increase of sum of longest diameters of target lesions (compared to initial on study baseline). The sum must also be at an increase of at least 5mm or one or more new lesions that are considered metastatic disease
Up to 1 Year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Duration of Therapy
Time Frame: Up to 5 years
The median Duration of therapy was measured. Participants with stable disease + PR allowed to continue; participants with progression were taken off therapy.
Up to 5 years
Overall Survival
Time Frame: Up to 1 Year
Time from beginning of treatment until death, or one year, whichever comes first.
Up to 1 Year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peter Anderson

Investigators

  • Principal Investigator: Peter M Anderson, MD, PhD, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 2, 2017

Primary Completion (Actual)

May 19, 2023

Study Completion (Actual)

May 19, 2023

Study Registration Dates

First Submitted

January 25, 2017

First Submitted That Met QC Criteria

January 25, 2017

First Posted (Estimated)

January 27, 2017

Study Record Updates

Last Update Posted (Estimated)

November 26, 2024

Last Update Submitted That Met QC Criteria

November 4, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CASE2716

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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