Phase 1 Study of PLX7486 as Single Agent in Patients With Advanced Solid Tumors
|Solid Tumor Tumors of Any Histology With Activating Trk (NTRK) Point or NTRK Fusion Mutations Tenosynovial Giant Cell Tumor||Drug: PLX7486 TsOH||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase 1 Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX7486 as a Single Agent in Patients With Advanced Solid Tumors|
- Safety of PLX7486 as single agent as measured by adverse events and serious adverse events. [ Time Frame: 1 year ]
- Area under the plasma concentration-time curve [AUC0-t, AUC0-inf] [ Time Frame: 1 year ]Area under the plasma concentration-time curve [AUC0-t, AUC0-inf] will be used to assess the pharmacokinetic profile of PLX7486.
- Peak concentration (Cmax) [ Time Frame: 1 year ]Peak concentration (Cmax) will be used to assess the pharmacokinetic profile of PLX7486.
- Time to peak concentration (Tmax) [ Time Frame: 1 year ]Time to peak concentration (Tmax) will be used to assess the pharmacokinetic profile of PLX7486.
- Half life (t1/2) [ Time Frame: 1 year ]Half life (t1/2) will be used to assess the pharmacokinetic profile of PLX7486.
- Terminal elimination rate constant (Kel) [ Time Frame: 1 year ]Terminal elimination rate constant (Kel) will be used to assess the pharmacokinetic profile of PLX7486.
- Duration of response (DOR) [ Time Frame: 1 year ]Duration of response is defined as the number of days from the date of initial response (PR or better) to the date of first documented disease progression/relapse or death, whichever occurs first.
- Progression-Free Survival (PFS) [ Time Frame: 6 month ]Progression-free survival (PFS) is defined as the number of days from start of therapy to the date of documented disease progression/relapse, whichever occurs first.
- Overall Response Rate (ORR) [ Time Frame: 1year ]
- Overall Survival (OS) [ Time Frame: 1 year ]
|Study Start Date:||August 2013|
|Estimated Study Completion Date:||August 2021|
|Estimated Primary Completion Date:||February 2021 (Final data collection date for primary outcome measure)|
Experimental: PLX7486-TsOH, Dose escalation and RP2D
Part 1: Open-label, sequential PLX7486-TsOH single-agent dose escalation in approximately 60 patients with solid tumors.
Part 2c (not yet recruiting): Extension cohort of single agent PLX7486-TsOH at the RP2D in patients with advanced non-resectable tumors of any histology with activating Trk (NTRK) point or NTRK fusion mutations or with unresectable, locally advanced or refractory Tenosynovial giant cell tumor (TGCT), including metastatic disease, in approximately 30 patients.
Drug: PLX7486 TsOH
PLX7486 TsOH capsules, 50mg
Part 1. Open-label, sequential PLX7486 TsOH single-agent dose escalation in approximately 60 patients with solid tumors.
Part 2c. Based upon safety and clinical activity observations, an extension cohort is planned at the RP2D of single-agent PLX7486 TsOH in approximately 30 patients with:
- Advanced, non-resectable tumors of any histology with their growth driven by CSF-1R activity or with activating Trk (NTRK) point or NTRK fusion mutations (e.g., mammary analogue secretory carcinoma, secretory breast cancer, papillary thyroid cancer, congenital fibrosarcoma, congenital mesoblastic nephroma, lung cancer, melanoma, and colon cancer) or underlying pathology or pathophysiology that suggests that NTRK signaling may be playing a significant role in disease (e.g., TrkC/NT3 overexpression in adenoid cystic carcinoma, TrkB/BDNF overexpression in non-small cell lung cancer) AND who have received prior treatment, if there is a known therapy that results in increased survival for that particular disease OR
- Unresectable, locally advanced or refractory TGCT (including metastatic disease)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01804530
|Contact: Oscar Alcantar||Oalcantar@plexxikon.com|
|United States, California|
|Ronald Reagan UCLA Medical Center||Recruiting|
|Los Angeles, California, United States, 90095|
|United States, Maryland|
|John Hopkins Sidney Kimmel Comprehensive Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21231|
|United States, Massachusetts|
|Massachusetts General Hospital Cancer Center||Recruiting|
|Boston, Massachusetts, United States, 02114|
|United States, South Carolina|
|Medical University of South Carolina||Recruiting|
|Charleston, South Carolina, United States, 29425|