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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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by Taiho Oncology, Inc.
Sponsor:
Information provided by (Responsible Party):
Taiho Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT02052778
First received: January 23, 2014
Last updated: November 3, 2015
Last verified: November 2015
  Purpose

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.


Condition Intervention Phase
Solid Tumors
Multiple Myeloma
Drug: TAS-120
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Taiho Oncology, Inc.:

Primary Outcome Measures:
  • 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).


Estimated Enrollment: 835
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)
Arms Assigned Interventions
Experimental: TAS-120
TAS-120 capsules, oral, dose-escalating, 21-day cycle
Drug: TAS-120

Detailed Description:

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:

Primary

• 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.

Secondary

  • 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.

Secondary

•To investigate the safety of TAS-120.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Provide written informed consent.

Is ≥18 years of age.

Patients with confirmed advanced metastatic solid tumor(s) with or without abnormalities of FGF/FGFR who have failed all standard therapies or for whom standard therapy does not exist.

Patients with confirmed multiple myeloma with amplification, mutation or translocation or other associated abnormalities of FGF/FGFR who have failed all standard therapies or for whom standard therapy does not exist.

Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

Women of child-bearing potential must have a negative pregnancy test

Exclusion Criteria:

History of endocrine alteration of calcium-phosphorus homeostasis.

History of ectopic mineralization/calcification

Current evidence of corneal disorder/keratopathy

History or current evidence of cardiac arrhythmia and/or conduction abnormality.

QTc > 470 msec on ECG conducted during Screening period

Treatment with any of the following within the specified time frame prior to the first dose of TAS-120:

  1. Major surgery within the previous 4 weeks
  2. Radiotherapy for extended field within 4 weeks
  3. Any noninvestigational anticancer therapy within 3 weeks
  4. Any medication administered within 7 days prior to first dose of TAS-120 that is known to affect QT interval
  5. Any investigational agent received either concurrently or within the previous 30 days.

A serious illness or medical condition(s)

Known hypersensitivity to TAS-120 or any drugs similar to it in structure or class.

Pregnant or lactating female.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02052778

Contacts
Contact: Robert Winkler, MD 855-598-8259 rwinkler@taihooncology.com

Locations
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         
Australia
Royal Melbourne Hospital Recruiting
Victoria, Australia
Contact: Ben Tran, MBBS, FRACP         
Principal Investigator: Ben Tran, MBBS, FRACP         
France
Institute Goustave-Roussy Recruiting
Paris, France
Contact: Jean-Charles Soria, MD, PhD         
Principal Investigator: Jean-Charles Soria, MD, PhD         
Spain
Vall D'Hebron University Hospital Recruiting
Barcelona, Spain
Principal Investigator: Joseph Tabernero, MD, PhD         
United Kingdom
Sarah Cannon Research Institute Recruiting
London, United Kingdom
Contact: Tobias Arkenau, MD, PhD         
Principal Investigator: Tobias Arkenau, MD, PhD         
Sponsors and Collaborators
Taiho Oncology, Inc.
Investigators
Study Director: Robert Winkler, MD Taiho Oncology, Inc.
  More Information

Responsible Party: Taiho Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02052778     History of Changes
Other Study ID Numbers: TPU-TAS-120-101
Study First Received: January 23, 2014
Last Updated: November 3, 2015

Keywords provided by Taiho Oncology, Inc.:
Breast Cancer
Non Small Cell Lung Cancer
Gastric Cancer
Multiple Myeloma
FGF
FGFR
FGFR abnormality
TAS-120
Dose Escalation

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Congenital Abnormalities
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on March 24, 2017