A First-in-man Phase I/II Study of Oral ONC201 in Patients With Advanced Cancer
ONC201 is a new potential drug that kills cancer cells but not normal cells in laboratory studies. This clinical trial will be the first evaluation of ONC201 in humans and will enroll patients with advanced cancer. This trial includes a phase I portion that will evaluate the safety of ONC201 and the recommended dose for the phase II portion. The phase II portion will evaluate the initial efficacy profile of ONC201 in select types of cancer.
Advanced Colorectal Cancer
Advanced Triple-negative Breast Cancer
Advanced Non-small Cell Lung Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A First-in-man Phase I/II Single-agent Open-label Dose-escalation Study of Every Three-week Dosing of Oral ONC201 in Patients With Advanced Cancer and Limited Treatment Options|
- In Phase I, to determine the recommended phase II doses of ONC201. [ Time Frame: Participants will be followed for the duration of the study, an expected average of 6 months. ] [ Designated as safety issue: Yes ]
- In phase II, Progression-free survival of patients treated with ONC201. [ Time Frame: from enrollment until first documented progression or date of death from any cause, whichever came first, assessed up to 100 months. ]
|Study Start Date:||June 2014|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Oral ONC201 will be administered once every three weeks at various doses.
ONC201 capsules will be administered orally once every three weeks with flat dosing. Dosage will be given according to a modified Fibonacci sequence with the anticipated starting dose being 125 mg.
Other Name: TIC10
ONC201 (TIC10) is a first-in-class small molecule that inactivates the Ras effector target kinases, Akt and ERK, selectively in tumor, but not normal, cells to safely trigger cancer cell death. The dual inactivation of Akt and ERK by ONC201 results in broad-spectrum cytotoxic activity that includes activation of TRAIL-mediated apoptotic and other downstream antitumor effects to produce a potent antitumor response. The safety margin (ratio of therapeutic dose to lowest dose with a mild adverse event) of ONC201 is at least 10-fold in rats and dogs in GLP toxicology. The efficacy of ONC201 has been consistently demonstrated in multiple in vitro, ex vivo, and in vivo preclinical cancer models. Favorable attributes of ONC201 observed in preclinical models include antitumor efficacy with infrequent administration, broad-spectrum activity independent of mutations or tumor type, orally active, high safety margins, synergistic activity with many approved therapies, highly stable, highly water soluble, and ability to penetrate the blood-brain barrier. In the phase I portion of the trial, the hypothesis is that ONC201 will exhibit an acceptable safety profile in patients with advanced cancer. In the phase II portion of the trial, the hypothesis is that ONC201 will show preliminary signs of efficacy in patients with advanced cancer as defined by endpoints that include progression-free survival, response rate, biomarkers, and overall survival.
|Contact: Jason Faris, MDemail@example.com|
|United States, Massachusetts|
|Massachusetts General Hospital||Not yet recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Keith Flaherty, MD 617-724-4800 firstname.lastname@example.org|
|Principal Investigator: Jason Faris, MD|
|Principal Investigator:||Jason Faris, MD||Massachusetts General Hospital|