ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma

Summary

Background: The new drug ONC201 have been shown to kill breast cancer and endometrial cancer cells in the laboratory. The exact mechanism of action is not completely clear yet, but the ONC201 destroys the mitochondria inside the cells. Blocking mitochondrial activity may kill tumor cells, which would shrink tumors. Researchers want to see if ONC201 helps shrink tumors of certain breast or endometrial cancers and if that effect is maintained. Objective: To see if ONC201 shrinks tumors with a lasting effect. Eligibility: Adults ages 18 and older who have metastatic breast cancer (hormone-positive or triple-negative) or metastatic endometrial cancers. Design: Participants will be screened with: * Medical history * Physical exam * Heart, blood, and urine tests * Computed tomography (CT) and bone scans * Review of medical report and tumor sample * Participants will have a tumor biopsy before starting treatment and after 5 weeks taking the study drug. A scan or ultrasound may be used to guide the biopsy. Patients will receive local anesthetic and a needle will remove a small piece of tumor. * The study will be done in 28-day cycles. Every day 1 of each cycle participants will repeat most screening tests, will be seen by the physician and receive a supply of the study drug. * Participants will take the study drug by mouth once every 7 days. They will keep a diary of when they take the drug and any side effects. During cycle 1, participants will get weekly calls to discuss their health and symptoms. Images will be repeated every 2 cycles to evaluate response to the treatment.

Timeline

Start

2018-01-17

Primary completion

2021-03-18

Completion

2021-10-07

Publications

• Background Greer YE, Lipkowitz S. TIC10/ONC201: a bend in the road to clinical development. Oncoscience. 2015 Feb 20;2(2):75-6. doi: 10.18632/oncoscience.133. eCollection 2015. No abstract available.
• Background Endo Greer Y, Lipkowitz S. ONC201: Stressing tumors to death. Sci Signal. 2016 Feb 16;9(415):fs1. doi: 10.1126/scisignal.aad7955.
• Background Stein MN, Bertino JR, Kaufman HL, Mayer T, Moss R, Silk A, Chan N, Malhotra J, Rodriguez L, Aisner J, Aiken RD, Haffty BG, DiPaola RS, Saunders T, Zloza A, Damare S, Beckett Y, Yu B, Najmi S, Gabel C, Dickerson S, Zheng L, El-Deiry WS, Allen JE, Stogniew M, Oster W, Mehnert JM. First-in-Human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors. Clin Cancer Res. 2017 Aug 1;23(15):4163-4169. doi: 10.1158/1078-0432.CCR-16-2658. Epub 2017 Mar 22.
• Atkins SLP, Greer YE, Jenkins S, Gatti-Mays ME, Houston N, Lee S, Lee MJ, Rastogi S, Sato N, Burks C, Annunziata CM, Lee JM, Nagashima K, Trepel JB, Lipkowitz S, Zimmer AS. A Single-Arm, Open-Label Phase II Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma. Oncologist. 2023 Oct 3;28(10):919-e972. doi: 10.1093/oncolo/oyad164.

Drugs

Indications