Clinical Trials /

Phase 2 Study of ONC201 in Neuroendocrine Tumors

NCT03034200

Description:

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.

Related Conditions:
  • Central Nervous System Primitive Neuroectodermal Neoplasm
  • Cerebral Primitive Neuroectodermal Tumor
  • Clear Cell Sarcoma of Soft Tissue
  • Desmoplastic Small Round Cell Tumor
  • Ewing Sarcoma
  • Extraskeletal Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Neuroblastoma
  • Neuroendocrine Tumor
  • Paraganglioma
  • Primitive Neuroectodermal Tumor
  • Round Cell Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Study of ONC201 in Neuroendocrine Tumors
  • Official Title: Phase 2 Study of ONC201 in Neuroendocrine Tumors

Clinical Trial IDs

  • ORG STUDY ID: CASE2716
  • NCT ID: NCT03034200

Conditions

  • Recurrent Neuroendocrine Tumor
  • Metastatic Neuroendocrine Tumor

Interventions

DrugSynonymsArms
ONC201ONC201

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
ONC201Experimental625mg by mouth every 3 weeks for up to 1 year
  • ONC201

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must have recurrent or metastatic neuroendocrine tumor including A) Cohort A
             . Pheochromocytoma-paraganglioma (PC-PG). N=12. B) Cohort B. Other neuroendocrine
             cancer varieties as characterized by expression of neuroendocrine markers on tumor
             tissue including cluster of differentiation 56 (CD56), synaptophysin,
             bombesin/gastrin-releasing peptide receptor, chromogranin and/or presence of a
             detectable serum or urine biomarker (3-methoxytyramine, normetanephrine,
             metanephrines, homovanillic acid (HVA), vanillylmandelic acid (VMA), dopamine, or
             bombesin/pro-gastrin releasing peptide). Varieties may include neuroblastoma, Ewing
             sarcoma, neuroectodermal tumor, primitive neuroectodermal tumor (PNET), desmoplastic
             small round cell tumor, and small cell carcinoma, 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Tumor response according to RECIST Criteria
Time Frame:Up to 1 Year
Safety Issue:
Description: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

Measure:Average duration of lack of progression: Clinical response
Time Frame:Up to 1 Year
Safety Issue:
Description: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
Measure:Overall survival
Time Frame:Up to 1 Year
Safety Issue:
Description:time from beginning of treatment until death, or one year, whichever comes first.
Measure:Average change in anti-hypertensive medication
Time Frame:from beginning of treatment to 3 months
Safety Issue:
Description: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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Peter Anderson

Trial Keywords

  • Pheochromocytoma-paraganglioma
  • ONC201

Last Updated

January 25, 2017