Dose-escalation, Safety and Pharmacokinetic Study of Briciclib in Advanced Solid Tumors
The main objectives of this study are to determine the safety profile of briciclib, an experimental anti-cancer drug, as it is administered intravenously once weekly as escalating doses in adult patients with advanced cancer and solid tumors, and to determine the highest dose of briciclib that can be safely given. Secondary objectives are to determine how the amount of briciclib in circulation changes over time and how much briciclib gets into the urine for excretion, and to document potential anti-tumor effects of briciclib.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Dose-escalation Study of the Safety, Pharmacokinetics and Efficacy of Weekly Intravenous Briciclib in Patients With Advanced Solid Tumors|
- Number of patients with adverse events [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]Adverse events will be grouped by system organ class (SOC) and preferred term (PT) using the most recent version of the Medical Dictionary for Regulatory Activities (MedDRA), and will be summarized by worst grade according to NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
- Number of patients with Dose Limiting Toxicity (DLT) [ Time Frame: Up to 3 weeks ] [ Designated as safety issue: Yes ]Dose-limiting toxicity is defined as an adverse event that is considered to be drug-related and meets one of the Protocol definitions.
- Maximum Tolerated Dose [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]Maximum Tolerated Dose (MTD) will be defined during the Dose Escalation Stage based on evaluation of the number of patients with Dose-limiting Toxicity (DLT). The MTD will be used to determine the Recommended Phase 2 Dose (RPTD).
- Concentration of briciclib in the plasma [ Time Frame: 24 hours ] [ Designated as safety issue: No ]The amount of briciclib in the plasma of patients in the Recommended Phase 2 Dose (RPTD) Confirmation stage only will be measured by a validated Liquid Chromatography-Mass Spectroscopy (LC-MS) method. Pharmacokinetic parameters will be derived from the concentration versus time values.
- Concentration of briciclib in the urine [ Time Frame: 24 hours ] [ Designated as safety issue: No ]The amount of briciclib in the urine of patients in the Recommended Phase 2 Dose (RPTD) Confirmation stage only will be measured by a validated Liquid Chromatography-Mass Spectroscopy (LC-MS) method. Pharmacokinetic parameters will be derived from the concentration versus time values.
- Change in size of tumors [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Change in the overall tumor will be determined from the tumor burden at Baseline following Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Biomarker Concentration or Activity [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]An exploratory objective of this study is to evaluate the biological effect of briciclib on cell-cycle pathways, cyclin D1, and other potential surrogate biomarker(s) of efficacy and/or toxicity in tumor tissue and peripheral blood mononuclear cells (PBMNC).
|Study Start Date:||June 2014|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
The starting dose of briciclib in the Escalation Stage will be 17 mg/week, with subsequent dose escalation levels of 35 mg, 70 mg, 140 mg, 280 mg, 560 mg, and 1120 mg. The dose of briciclib in the RPTD Confirmation Stage will be the dose as determined during the escalation stage. At each dose level, briciclib will be administered as a 2-hour intravenous infusion, once-a-week per 3-week cycles.
Other Name: ON 013105
This will be a Phase I, 2-stage, open-label, dose-escalating, multicenter study of the 2-hour, once-a-week intravenous (IV) administration of briciclib in 3-week cycles, in up to 54 adult patients with advanced cancer and solid tumors. The study will be conducted in 2 stages: a dose-escalation stage to determine the Maximum Tolerated Dose (MTD) and a Recommended Phase 2 Dose (RPTD) confirmation stage. Patients with stable disease (SD) or response may remain treated on study until progression.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02168725
|Contact: Michael Kurman, MDfirstname.lastname@example.org|
|United States, Colorado|
|University of Colorado Hospital Anschutz Medical Campus||Recruiting|
|Aurora, Colorado, United States, 80045|
|Principal Investigator: Antonio Jimeno, MD, PhD|
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Principal Investigator: Wen W. Ma, MD|
|United States, Tennessee|
|Sarah Cannon Research Institute||Recruiting|
|Nashville, Tennessee, United States, 37203|
|Principal Investigator: Erika P. Hamilton, MD|
|Principal Investigator:||Antonio Jimeno, MD, PhD||University of Colorado, Denver|