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Phase 2 Study of ONC201 in Neuroendocrine Tumors

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ClinicalTrials.gov Identifier: NCT03034200
Recruitment Status : Recruiting
First Posted : January 27, 2017
Last Update Posted : July 31, 2019
Sponsor:
Information provided by (Responsible Party):
Peter Anderson, Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE January 25, 2017
First Posted Date  ICMJE January 27, 2017
Last Update Posted Date July 31, 2019
Actual Study Start Date  ICMJE August 2, 2017
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2017)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03034200 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2017)
  • 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
  • Overall survival [ Time Frame: Up to 1 Year ]
    time from beginning of treatment until death, or one year, whichever comes first.
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 2 Study of ONC201 in Neuroendocrine Tumors
Official Title  ICMJE Phase 2 Study of ONC201 in Neuroendocrine Tumors
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 neuroendocrine cancers including PC-PG.

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.

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Neuroendocrine Tumor
  • Metastatic Neuroendocrine Tumor
Intervention  ICMJE Drug: ONC201
625mg ONC201 will be given weekly for up to one year or until progression.
Study Arms  ICMJE Experimental: ONC201
625mg by mouth weekly for up to 1 year
Intervention: Drug: ONC201
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 25, 2017)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2020
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects must have unresectable, recurrent, locally advanced, or metastatic neuroendocrine tumor including A) Cohort A. Unresectable, recurrent, locally advanced, or metastatic Pheochromocytoma-paraganglioma (PC-PG) who have failed or are refractory to available therapies . N=12. B) Cohort B will include only patients with unresectable, locally advanced or metastatic tumors who have failed or are refractory to available therapyOther neuroendocrine cancer varieties as characterized by expression of neuroendocrine markers on tumor tissue including CD56, synaptophysin, , chromogranin and/or presence of a detectable serum or urine biomarker (3-methoxytyramine, normetanephrine, metanephrines, homovanillic acid (HVA), vanillylmandelic acid (VMA), and dopamine, Varieties will include neuroblastoma, Ewing sarcoma, neuroectodermal tumor, clear call sarcoma, myoepithelial tumor, primitive neuroectodermal tumor (PNET), desmoplastic small round cell tumor, round cell sarcoma, and unresectable, metastatic or locally advanced , well-differentiated neuroendocrine tumors who have relapsed or are refractory to at least 2 systemic therapies (e.g. lanreotide, sunitinib, or everolimus). Patients with small cell carcinomas will not be included in this clinical trial.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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Peter M Anderson, MD, PhD 216-445-4007 andersp@ccf.org
Contact: Stacey Zahler, DO 216-445-3588 zahlers@ccf.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03034200
Other Study ID Numbers  ICMJE CASE2716
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Peter Anderson, Case Comprehensive Cancer Center
Study Sponsor  ICMJE Peter Anderson
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Peter M Anderson, MD, PhD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
PRS Account Case Comprehensive Cancer Center
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP