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Phase 2 Study of ONC201 in Neuroendocrine Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03034200
Recruitment Status : Recruiting
First Posted : January 27, 2017
Last Update Posted : August 4, 2020
Sponsor:
Information provided by (Responsible Party):
Peter Anderson, Case Comprehensive Cancer Center

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Recurrent Neuroendocrine Tumor Metastatic Neuroendocrine Tumor Drug: ONC201 Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Study of ONC201 in Neuroendocrine Tumors
Actual Study Start Date : August 2, 2017
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: ONC201 phase 2 d1d2 weekly cohort
625 mg ONC201 by mouth daily for 2 consecutive days weekly
Drug: ONC201
625mg ONC201 will be given on two consecutive days each week




Primary Outcome Measures :
  1. 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



Secondary Outcome Measures :
  1. Average duration of lack of progression: Clinical response [ Time Frame: Up to 1 Year ]
    Average time from beginning of treatment to progression, death, or one year, whichever comes first. An underlying clinical benefit rate of 25% would indicate that ONC201 has a therapeutic effect, whereas an underlying rate <5% would indicate a lack of activity

  2. Overall survival [ Time Frame: Up to 1 Year ]
    time from beginning of treatment until death, or one year, whichever comes first.

  3. Average change in anti-hypertensive medication [ Time Frame: from beginning of treatment to 3 months ]
    to achieve this secondary endpoint of anti-hypertensive medication reduction in PC-PG subjects (N=12) data at 3 months will be required. An underlying clinical benefit rate of 25% would indicate that ONC201 has a therapeutic effect, whereas an underlying rate <5% would indicate a lack of activity



Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  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%


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03034200


Contacts
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Contact: Peter M Anderson, MD, PhD 216-308-2706 andersp@ccf.org
Contact: Stacey Zahler, DO 216-445-3588 zahlers@ccf.org

Locations
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United States, Ohio
Cleveland Clinic Pediatric and Taussig Cancer Institute, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Peter M Anderson, MD, PhD    216-308-2706    andersp@ccf.org   
Principal Investigator: Peter M Anderson, MD, PhD         
Sponsors and Collaborators
Peter Anderson
Investigators
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Principal Investigator: Peter M Anderson, MD, PhD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Additional Information:
Publications of Results:
Other Publications:

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Responsible Party: Peter Anderson, Site Principal Investigator, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03034200    
Other Study ID Numbers: CASE2716
First Posted: January 27, 2017    Key Record Dates
Last Update Posted: August 4, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Peter Anderson, Case Comprehensive Cancer Center:
Pheochromocytoma-paraganglioma
ONC201
Additional relevant MeSH terms:
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Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue