A Dose Finding Study Followed by a Safety and Efficacy Study in Patients With Advanced Solid Tumors or Multiple Myeloma With FGF/FGFR-Related Abnormalities
The purpose of this study is to determine the safety of TAS-120 and determine the most appropriate dose for the subsequent phase 2 safety and efficacy study in patients with advanced solid tumors and multiple myeloma with genetic abnormalities.
The progression of cancers is caused by a complex series of multiple genetic and molecular events leading to changes in the patients DNA. The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway is important for normal organ, vascular and skeletal development. However, FGFR gene abnormalities have been linked to various cancers.
TAS-120 is a highly potent, selective small molecule inhibitor of FGFR and is therefore is being studied as a therapy for cancer.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Dose-Finding Phase 1 Study of TAS-120 in Patients With Advanced Solid Tumors With or Without Fibroblast Growth Factor/Receptor (FGF/FGFR)-Related Abnormalities Followed By A Phase 2 Study in Patients With Advanced Solid Tumors or Multiple Myeloma With FGF/FGFR-Related Abnormalities|
- Safety and tolerability of TAS-120 [ Time Frame: Safety monitoring will begin at the time of the first dose of TAS-120, and will continue for 30 days after the last dose of TAS-120, until the initiation of another anticancer therapy, or up to 4 years, whichever occurs first. ]
Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.03) will be used.
Assessed by number and severity of adverse events, physical exam, vital signs, weight, ECOG Performance Status, urinalysis, ophthalmological examination, neurological examination: electrocardiogram evaluation, hematology and coagulation, serum chemistry.
- Tumor assessments according to RECIST guidelines (version 1.1, 2009) [ Time Frame: Computed tomography scans will be performed at week 6, 12 and every 9 weeks thereafter until until treatment discontinuation, or up to 4 years, whichever occurs first. ]The determination of antitumor efficacy will be based on objective tumor assessments made by the investigator according to the revised RECIST guidelines (version 1.1, 2009) of unidimensional evaluation.
- Multiple Myeloma Assessments [ Time Frame: Multiple myeloma assessments for response will be conducted at the beginning of each cycle, i.e. every 3 weeks, until treatment discontinuation, or up to 4 years, whichever occurs first. ]Serum, urine protein electrophoresis and serum free light chain(SPEP/UPEP/SFLC) will be obtain to assess Multiple myeloma using The International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma (Durie et al, 2006).
|Study Start Date:||July 2014|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||September 2018 (Final data collection date for primary outcome measure)|
TAS-120 capsules, oral, dose-escalating, 21-day cycle
Background and rationale for study:
- Activating fibroblast growth factor receptor (FGFR) gene abnormalities are reported in various cancers including non-small cell lung cancer (NSCLC) (FGFR1 amplification), breast (FGFR1 and 2 amplification), gastric (FGFR2 amplification), bladder (FGFR3 activating mutation or gene translocation), endometrial (FGFR2 activating mutation), multiple myeloma (FGFR3 gene translocation), and rhabdomyosarcoma (FGFR4-activating mutation).
- TAS-120 is a novel, highly potent and selective small molecule FGFR inhibitor.
Phase 1 Dose Escalation:
• To investigate the safety and to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of TAS-120 in patients with advanced solid tumors with or without FGF/FGFR abnormalities for whom no available therapy is likely to convey clinical benefit.
- To investigate the clinical pharmacokinetics (PK) of TAS-120.
- To investigate the clinical pharmacodynamics of TAS-120.
- To determine any preliminary antitumor activity observed with TAS-120.
Phase 1 Expansion and Phase 2:
Primary •To investigate the efficacy of the TAS-120 RP2D in patients with advanced solid tumors or multiple myeloma, with FGF/FGFR abnormalities for whom no available therapy is likely to convey clinical benefit.
•To investigate the safety of TAS-120.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02052778
|Contact: Robert Winkler, MDfirstname.lastname@example.org|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator: Lecia Sequist, MD, MPH|
|United States, Texas|
|MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Funda Meric-Bernstam, MD|
|Principal Investigator: Funda Meric-Bernstam, MD|
|Royal Melbourne Hospital||Recruiting|
|Contact: Ben Tran, MBBS, FRACP|
|Principal Investigator: Ben Tran, MBBS, FRACP|
|Contact: Jean-Charles Soria, MD, PhD|
|Principal Investigator: Jean-Charles Soria, MD, PhD|
|Vall D'Hebron University Hospital||Recruiting|
|Principal Investigator: Joseph Tabernero, MD, PhD|
|Sarah Cannon Research Institute||Recruiting|
|London, United Kingdom|
|Contact: Tobias Arkenau, MD, PhD|
|Principal Investigator: Tobias Arkenau, MD, PhD|
|Study Director:||Robert Winkler, MD||Taiho Oncology, Inc.|