ONC206 (JZP3507) for advanced pheochromocytoma and paraganglioma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a two-stage Phase 2, open-label study of ONC206 given as oral monotherapy in adults with advanced, unresectable pheochromocytoma or paraganglioma and measurable disease. In Stage 1 participants receive 150 mg twice daily on three consecutive days per week in each 28-day cycle, with an initial cohort followed by an expansion cohort if predefined responses are seen. If Stage 1 meets response criteria, Stage 2 randomizes participants 1:1 to one of two ONC206 dose levels to further compare activity and safety. Safety, tolerability, and anti-tumor activity will be monitored using standard labs, adverse event reporting, and RECIST v1.1 tumor measurements.

Why it matters

Who can join: the full rules

Inclusion criteria:

1. Has histologically confirmed pheochromocytoma or paraganglioma that is unresectable as determined by the Investigator.
2. Has failed, is not a candidate for, or has declined standard of care treatment for PCPG. There is no limit on the number of prior systemic therapies.
3. Must have measurable disease per RECIST v1.1, as assessed by the Investigator.
4. Has adequately controlled blood pressure defined as blood pressure ≤150/90 mmHg and with no change in antihypertensive medications (for participants with concomitant hypertension) for at least 14 days before the first dose of study treatment.
5. Is ≥18 years of age.
6. Is able to swallow oral tablets.
7. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2, assessed within 7 days before the first dose of study treatment.
8. Has laboratory test results meeting the following parameters within 14 days before the first dose of study treatment
9. Has an expected survival of at least 12 weeks, as predicted by the physician.
10. Has pharmacologic control of catecholamine-associated symptoms if participant has functional disease.

Exclusion criteria:

1. Has known hypersensitivity to ONC206 or any excipient used in the ONC206 study treatment formulation.
2. Has active cardiac disease/condition including any of the following:

   1. Corrected QT interval (QTc) \>480 msec (based on the mean from triplicate electrocardiogram \[ECGs\] performed during Screening).
   2. History of documented congestive heart failure (New York Heart Association function classification III-IV).
   3. Unstable angina, acute myocardial infarction, or arterial bypass or percutaneous transluminal coronary angioplasty within 6 months before the first dose of study treatment.
3. Has previous exposure to ONC206 or dordaviprone (ONC201) from any source.
4. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Exceptions include participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, or Von Hippel-Lindau disease-associated tumors that do not require immediate surgery or intervention.
5. Has received any of the following interventions within the specified time periods before the first dose of study treatment or plans to receive any of the following interventions during study participation:

   * a. Any prior anticancer therapy or investigational agents within 4 weeks or 5 half-lives, whichever is shorter. Note: Denosumab and zoledronic acid are permissible.

     \*\*i. Any treatment with somatostatin analog or lanreotide within 21 days before the baseline Positron Emission Tomography (PET) scan.
   * b. Strong cytochrome P450 (CYP) inhibitors within 14 days. c. Strong CYP inducers within 14 days. d. Any radiotherapy within 14 days. e. Any major surgery, open biopsy or significant traumatic injury within 1 month (30 days).
6. Is pregnant, breastfeeding, or planning to become pregnant while receiving study treatment or within 3 months after the last dose.
7. Has uncontrolled intercurrent illness or any other medical, psychiatric, or social condition that, in the opinion of the Investigator, may interfere with participant safety or the ability to comply with study requirements.
8. Has unresolved toxicities from previous locoregional, systemic, or any other therapies, defined as toxicities (other than Grade ≤2 neuropathy or alopecia) not yet resolved to the National Cancer Institute Common Terminology Criteria for Adverse Events Grade ≤1, or baseline and considered clinically significant; consult with Medical Monitor.
9. Has an active infection that requires systemic therapy.

Where it's running

• UCLA
  Los Angeles, California, United States Recruiting
• Stanford
  Palo Alto, California, United States Recruiting
• U of Colorado
  Aurora, Colorado, United States Recruiting
• U of Michigan
  Ann Arbor, Michigan, United States Recruiting
• Mayo-Rochester
  Rochester, Minnesota, United States Recruiting
• Washington University
  St Louis, Missouri, United States Recruiting

Study contacts

• Study coordinator: Clinical Trial Disclosure & Transparency
• Email: ClinicalTrialDisclosure@jazzpharma.com
• Phone: 215-832-3750

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.