A Two Part, Multicenter, Open-label Study of TEN-010 Given Subcutaneously
TEN-010 is a small molecule, bromodomain and extra-terminal domain (BET) bromodomain inhibitor. This study is designed to characterize the safety, tolerability, pharmacokinetics and anti-tumor activity of TEN-010 in patients who are refractory or intolerant to standard/approved therapies. This first-in-human study of TEN-010 will be conducted in two parts: dose escalation and dose expansion. For dose escalation (Part A), a standard "3+3" design will be used in which successive cohorts of three or more patients with advanced solid tumor malignancies will be treated at escalating doses until a maximum tolerated dose (MTD) is identified. For the dose expansion part of the study (Part B), a subset of patients with advanced solid malignancies will be treated with TEN-010 at the MTD (or the highest dose tested if the MTD is not defined) to further characterize safety and biological effect. In addition, up to 10 patients with nuclear protein in testis (NUT) midline carcinoma (NMC) will be permitted to enroll in a substudy of the protocol.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Two Part, Phase 1, Multicenter, Open-label Study of TEN-010 Given Subcutaneously. Part A: A Dose-Escalation Study in Patients With Advanced Solid Tumors. Part B: An Expansion Cohort in Patients With Selected Malignancies.|
- Maximum tolerated dose and dose-limiting toxicities as determined in Part A. [ Time Frame: End of Cycle 1 (Day 28) ] [ Designated as safety issue: Yes ]Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.03).
- Safety parameters [ Time Frame: Parts A and B: at a minimum Days 1, 8, 15, 22 of each treatment cycle. ] [ Designated as safety issue: Yes ]Physical examination, clinical safety laboratory tests, assessment of adverse events, Eastern Cooperative Oncology Group Performance Status (ECOG PS), chest X-ray, Electrocardiogram (ECG), vital signs, and concomitant medication review.
- Pharmacokinetics [ Time Frame: Cycle 1 Day 1, Day 8, Day 15, Cycle 2 Day 1, Day 15, Day 22. ] [ Designated as safety issue: No ]Plasma levels of TEN-010 will be measured during the treatment and follow-up periods. Pharmacokinetic variables to be calculated are AUC, Cmax, and Tmax.
- Efficacy [ Time Frame: At baseline, at the end of Cycle 2 (2 months), and every 2 cycles (2 months) thereafter until disease progression or death. ] [ Designated as safety issue: No ]Response to treatment evaluated using the Response Evaluation Criteria in Solid Tumors guidelines (RECIST 1.1).
|Study Start Date:||October 2013|
|Estimated Study Completion Date:||February 2015|
|Estimated Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
Safety, tolerability and pharmacokinetics of TEN-010 in Patients with Advanced Solid Malignancies.
This is a Phase 1 non-randomized, dose-escalating, open label, multi-center study to be conducted in two parts (Part A and Part B). A maximum of 56 patients aged 18 years or older with histologically confirmed advanced solid tumors with progressive disease requiring therapy will be enrolled in the study. It is expected that approximately 36 patients will be enrolled in 6 cohorts of up to 6 patients per cohort in Part A of the study and 20 additional patients will be enrolled in Part B of the study. Up to 10 patients with NMC may be enrolled as part of a substudy within the protocol.
|United States, Massachusetts|
|Dana Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Andrew Wolanski 617-632-6623 email@example.com|
|Principal Investigator: Geoff Shapiro, MD|
|United States, Michigan|
|Karmanos Center Institute||Recruiting|
|Detroit, Michigan, United States, 48201|
|Contact: Karen Forman, BAA, CCRP 313-576-8096 firstname.lastname@example.org|
|Principal Investigator: Muaiad Kittaneh, MD|
|Study Director:||Steve Landau, MD||Tensha Therapeutics|