Determination of the Relative Bioavailability of ARQ 197 Tablet Formulation With Capsule C Formulation as a Reference in Subjects With Advanced Solid Tumors

An Open-Label, Phase 1, Randomized, Two-Treatment, Two-Period, Two-Way Crossover, Relative Bioavailability Study Of A Capsule And A Tablet Formulation Of ARQ 197 In Subjects With Advanced Solid Tumors

This is a Phase 1, randomized, open label, 2 treatment, 2 period, 2-way crossover study, with an extension phase design in which the steady state PK of ARQ 197 will be investigated using the tablet administered in fed state (test treatment) and capsule administered at least 1 hour before or 2 hours after a meal (reference treatment) in subjects with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Tivantinib (ARQ 197) Capsule; Drug: Tivantinib (ARQ 197) Tablet; Drug: Tivantinib (ARQ 197) Capsule D, oral

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90404
      • Premiere Oncology
  • Florida
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute (SCRI)
  • Texas
    • San Antonio, Texas, United States, 78229
      • START - South Texas Accelerated Research Therapeutics, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must have a histologically or cytologically confirmed advanced solid tumor at screening.
• Male or female equal or greater than 18 years of age.
• All female subjects of childbearing potential must each have a negative serum pregnancy test result before initiating study treatment.
• An Eastern Cooperative Oncology Group (ECOG) performance status equal or less than 2

• Adequate bone marrow, liver, and renal function, defined as:

  • Platelet count equal or greater than 75 x 10(9)/L
  • Hemoglobin (Hb) equal or greater than 9.0 g/dL
  • Absolute neutrophil count (ANC) equal or greater than 1.5 x 10(9)/L
  • Total bilirubin equal or less than 1.5 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) equal or less than 3 x ULN (equal or less than 5 x ULN for subjects with liver metastases)
  • Serum creatinine equal or less than 1.5 x ULN

Exclusion Criteria:

• History of cardiac disease: Active coronary artery disease (CAD), defined as myocardial infarction (MI), unstable angina, coronary bypass graft (CABG), or stenting within 6 months prior to study entry (an MI that occurred > 6 months prior to study entry is permitted)
• Evidence of uncontrolled bradycardia or other cardiac arrhythmia defined as equal or greater than Grade 2 according to NCI CTCAE, version 4.0, or uncontrolled hypertension
• Active, clinically serious infection(s) defined as equal or greater than Grade 2 according to NCI CTCAE, version 4.0.
• Known metastatic brain or meningeal tumors, unless the subject is > 3 months from definitive therapy and clinically stable (supportive therapy with steroids or anticonvulsant medications is allowed) with respect to the tumor at the time of first dose of study drug.
• Prior therapy with mesenchymal-epithelial transition factor (c-MET) inhibitors, including ARQ 197.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARQ 197 Capsule, oral; Oral BID 360 mg dose (Capsule C: 6 X 60 mg) of ARQ 197 at least 1 hour before or 2 hours after a meal for 7 days	Drug: Tivantinib (ARQ 197) Capsule; Oral BID 360 mg dose (Capsule C: 6 X 60 mg) of ARQ 197 at least 1 hour before or 2 hours after a meal for 7 days; Other Names: Tivantinib
Experimental: ARQ 197 Tablet, oral; Oral BID 360 mg dose (Tablet: 3 x 120 mg) of ARQ 197 under fed conditions for 7 days	Drug: Tivantinib (ARQ 197) Tablet; Oral BID 360 mg dose (Tablet: 3 x 120 mg) of ARQ 197 under fed conditions for 7 days; Other Names: Tivantinib
Experimental: ARQ 197 Capsule D, oral; Oral BID 360 mg dose (Capsule D: 3 x 120 mg) of ARQ 197 under fed conditions in the extension phase	Drug: Tivantinib (ARQ 197) Capsule D, oral; Oral BID 360 mg dose (Capsule D: 3 x 120 mg) of ARQ 197 under fed conditions in the extension phase; Other Names: Tivantinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of the relative bioavailability of ARQ 197 tablet formulation with capsule C formulation	The primary endpoints are the area under the concentration time curve from time of dosing until 12 hours post-dose (AUC0-12) and maximum observed concentration in plasma (Cmax) of ARQ 197 following the administration of the tablet (fed conditions) and capsule formulation (at least 1 hour before or 2 hours after a meal).	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of additional pharmacokinetic parameters of ARQ 197 tablet formulation and capsule C formulation	Time until Cmax (tmax), apparent oral clearance (CL/F), and apparent volume of distribution (V/F) of ARQ 197, and if possible, minimum observed concentration (Cmin) and average observed concentration (Cavg) following the administration of the tablet (fed conditions) and capsule formulation (at least 1 hour before or 2 hours after a meal)	14 days

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Collaborators: ICON Clinical Research; ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: June 22, 2010
• First Submitted That Met QC Criteria: June 22, 2010
• First Posted (Estimate): June 23, 2010

Study Record Updates

• Last Update Posted (Actual): February 12, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Relative bioavailability; ARQ 197
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ARQ197-A-U157

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)