NCT03099499

Single Agent ONC201 in Recurrent or Metastatic Endometrial Cancer

A Phase 2 Study of Single Agent ONC201 in Recurrent or Metastatic Endometrial Cancer

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: Fox Chase Cancer Center · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

ONC201 is a small molecule which selectively targets the G protein-coupled receptor DRD2. Downstream of target engagement, ONC201 activates the integrated stress response (ISR) in tumor cell leading to inactivation of Akt and extracellular signal-regulated kinase (ERK) signaling as well as induction of the TRAIL pathway. ONC201 also inhibits dopamine receptor 2 (DRD2), resulting in anti-tumor responses in preclinical models. Single agent ONC201 has been examined in open-label Phase I studies in patients with advanced, treatment refractory solid malignancies. Due to its differential anti-proliferative and pro-apoptotic response in tumor cells, treatment was overall well tolerated, and the recommended phase II dose of ONC201 was set at 625mg every three weeks. An additional dose-escalation phase I study (NCT02609230) is further evaluating weekly versus three week dosing in patients with advanced solid tumors and multiple myeloma. Preliminary data from these phase I studies suggests a possible clinical benefit in patients with advanced, chemo-refractory endometrial cancers, with at least one mixed response noted in a patient with clear cell histology. Hypothesis: Single agent ONC201 will demonstrate clinical benefit in women with recurrent or metastatic endometrial cancers, especially in those women with alterations in the Phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of Rapamycin (mTOR) pathway.

Conditions

• Endometrial Cancer

Interventions

Type	Name	Description
DRUG	ONC201	ONC201 will be administered at a dose of 625 mg by mouth weekly until disease progression, unacceptable toxicity, or if the patient discontinues for any other reason. Radiologic tumor assessment would be performed at baseline, Cycle 3 Day 1, Cycle 5 Day 1, and at the end of every 3 cycles beyond cycle 5. All patients including those removed from the study due to unacceptable toxicity, will undergo radiologic tumor assessment at the time of discontinuation (End of treatment).

Timeline

• Start date: 2017-06-08
• Primary completion: 2020-09-09
• Completion: 2020-09-09
• First posted: 2017-04-04
• Last updated: 2024-12-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study