First-in-human Study of Oral TP-0903 (a Novel Inhibitor of AXL Kinase) in Patients With Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT02729298|
Recruitment Status : Recruiting
First Posted : April 6, 2016
Last Update Posted : January 16, 2018
TP-0903 is a novel oral inhibitor that targets AXL kinase. Preclinical studies have shown promising antitumor activity of TP-0903 as a single agent against a variety of tumor types in both in vitro and in vivo studies.
This first-in-human study is conducted to identify the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of TP-0903 administered orally to patients with advanced solid tumors.
The study will investigate the safety, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity profiles.
|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumors||Drug: TP-0903||Phase 1|
This is a phase 1, first-in-human, open-label, dose-escalation, safety, pharmacokinetics, and pharmacodynamic study of TP-0903 administered once daily for the first 21 out of 28 days.
There are 2 stages in this study. In Stage 1, sequential cohorts of three (3) patients will be treated with escalated doses until the MTD is established. In the absence of dose-limiting toxicities (DLTs), the dose will be increased using a modified Fibonacci dose escalation scheme. Once the MTD has been established, 2 additional cohorts of up to 10 patients each (20 additional patients total) may be enrolled at the MTD dose level for confirmation of safety (Stage 2).
Patients who successfully complete a 4-week treatment cycle without evidence of significant treatment-related toxicity or progressive disease will be permitted to continue to receive treatment with the same dose and dosing schedule.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||46 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I, First-in-human, Open-label, Dose-escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP-0903 Administered Daily for 21 Days to Patients With Advanced Solid Tumors|
|Actual Study Start Date :||December 14, 2016|
|Estimated Primary Completion Date :||March 2018|
|Estimated Study Completion Date :||June 2018|
Single daily dose by oral administration on Days 1-21 of a 28 day cycle
Stage 1: Single oral daily doses on Days 1-21 of each 28 day cycle. Starting dose is 1.5 mg/m2 with subsequent dose escalation using a modified Fibonacci dose escalation schema.
Stage 2: Upon confirmation of MTD, 2 additional cohorts of up 10 patients each (20 additional patients total) will receive single oral daily doses of this dose on Days 1-21 of each 28 day cycle.
- Incidence of dose-limiting toxicities (DLTs) and treatment emergent adverse events [ Time Frame: Cycle 1 (Day 1 through Day 28) ]
A DLT is defined as any one of the following events observed within Cycle 1:
Grade 3 or greater febrile neutropenia, Grade 4 nANC for 7 or greater consecutive days, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with clinically significant bleeding or that requires a platelet transfusion, Grade 3 or 4 non-hematologic AEs including nausea, vomiting, diarrhea, and electrolyte imbalances persisting for more than 48 hours despite optimal medical management, dosing delays of 2 weeks or greater due to treatment emergent adverse events or related severe laboratory test values
- Area under the plasma concentration-time curve from zero to infinity [AUC(0-inf)] of oral TP-0903 [ Time Frame: Blood will be taken from subjects at Cycle 1/Day 1 and Cycle1/Day 21at predose and 0.5, 1, 2, 4, 8, 24 hrs post dose and at 48 hrs post dose Day 21. ]Derived PK parameters by non-compartment analysis on Cycle 1, Days 1 and 21.
- Area under the plasma concentration-time curve from zero to last measured time point [AUC(0-last)] of oral TP-0903 [ Time Frame: Blood will be taken from subjects at Cycle 1/Day 1 and Cycle1/Day 21at predose and 0.5, 1, 2, 4, 8, 24 hrs post dose and at 48 hrs post dose Day 21. ]Derived PK parameters by non-compartment analysis on Cycle 1, Days 1 and 21.
- Peak plasma concentration (Cmax) of oral TP-0903 [ Time Frame: Blood will be taken from subjects at Cycle 1/Day 1 and Cycle1/Day 21at predose and 0.5, 1, 2, 4, 8, 24 hrs post dose and at 48 hrs post dose Day 21. ]Derived PK parameters by non-compartment analysis on Cycle 1, Days 1 and 21.
- Activity of TP-0903 on predictive biomarkers [ Time Frame: PBMCs and serum will be obtained prior to first dose on Day 1/Cycle 1 and at 2 and 24 hours after dosing and on Day 8 ]Assess biomarkers in tumor tissue, PBMCs and serum. The pharmacodynamic relationships of TP-0903 exposure with exploratory biomarkers will be quantified using the Spearman rank correlation statistic.
- Objective response rate using RECIST v1.1 [ Time Frame: Patients will be assessed on Day 22 after every two treatment cycles through study completion ]Baseline tumor assessment will be performed at screening and repeated at Cycle 2 and every even cycle thereafter.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02729298
|Contact: Holly Beever, BS, RNemail@example.com|
|Contact: Susan Smith, MSNfirstname.lastname@example.org|
|United States, Arizona|
|HonorHealth Research Institute||Recruiting|
|Scottsdale, Arizona, United States, 85258|
|Contact: Joyce Schaffer, RN 480-323-1339 email@example.com|
|Principal Investigator: Vivek Khemka, MD|
|United States, Texas|
|University of Texas Southwestern Medical Center||Recruiting|
|Dallas, Texas, United States, 75390|
|Contact: Yolanda Pitts firstname.lastname@example.org|
|Principal Investigator: Muhammad Beg, MD|
|University of Texas Science Center at San Antonio (UTHSCSA)||Recruiting|
|San Antonio, Texas, United States, 78229|
|Contact: CTRC 210-450-2872|
|Principal Investigator: John Sarantopoulos, MD|
|Study Director:||Stephen P Anthony, DO||Tolero Pharmaceuticals|