Effect of Tivantinib on the QTC Interval in Cancer Subjects

NCT01699061 | Completed Phase 1

• 1 other identifier: ARQ197-A-U159
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the effects of tivantinib on the QTc interval in patients with solid tumors

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• The time-matched difference in the QTcF interval at each timepoint after both single and multiple doses of tivantinib compared with placebo

  Triplicate ECG measurements of the QTc interval will be taken at Screening (4 sets each 1 hour apart) and pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post dose on Days 1, 2, and 5 (+3 days)

  Baseline and 1, 2, 3, 4, 6, 8, and 12 hours post dose on Days 1, 2, and 5 (+3 days)

Secondary Outcomes (3)

• Estimated change in baseline adjusted QT, corrected QT interval (QTcB), individually corrected QT interval (QTcI) (if possible), heart rate, PR, QRS, & RR intervals at timepoints after both single and multiple doses of tivantinib compared with placebo

  Baseline and 1, 2, 3, 4, 6, 8, and 12 hours post dose on Days 1, 2, and 5 (+3 days)

• Plasma pharmacokinetic (PK) profiles of tivantinib and major metabolites of tivantinib after both single and multiple doses of tivantinib.

  Baseline and 1, 2, 3, 4, 6, 8, and 12 hours post dose on Days 1, 2, and 5 (+3 days)

• Explore the tivantinib plasma concentration-QTc interval relationship

  Baseline and 1, 2, 3, 4, 6, 8, and 12 hours post dose on Days 1, 2, and 5 (+3 days)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo tablet administered with a meal twice a day on Day 1

Drug: Placebo

Tivantinib

EXPERIMENTAL

3 tivantinib tablets 120 mg administered twice daily with a meal starting on Day 2

Drug: Tivantinib

Interventions

Tivantinib DRUG

3 tivantinib tablets 120 mg administered twice daily with a meal starting on Day 2

Also known as: ARQ 197

Tivantinib

Placebo DRUG

Placebo tablet administered with a meal twice a day on Day 1

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a histologically or cytologically confirmed advanced solid tumor at Screening
• Male or female greater than or equal to 18 years of age
• Women of childbearing potential must have a negative pregnancy test performed prior to the start of study drug
• Subjects (male and female) of childbearing potential must agree to use double barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug. In addition, all female subjects of childbearing potential must have a negative pregnancy test result before initiating study treatment
• An Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2
• Adequate bone marrow and liver function, defined as:
• Platelet count greater than or equal to 100 × 109/L
• Hemoglobin greater than or equal to 9.0 g/dL
• Absolute neutrophil count greater than or equal to 1.5 × 109/L
• Total bilirubin less than or equal to 1.5 × upper limit of normal (ULN)
• Alanine aminotransferase and aspartate aminotransferase less than or equal to 3 × ULN (less than or equal to 5 × ULN for subjects with liver metastases)
• Serum creatinine less than or equal to 1.5 × ULN
• Electrolytes within normal limits, particularly potassium, magnesium, \& calcium. Supplementation is permitted as needed
• Subjects should be able to provide written informed consent, comply with protocol visits and procedures, be able to take oral medication, and not have any active infection or chronic co-morbidity that would interfere with therapy
• Subjects must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an IRB-approved ICF (including HIPAA authorization, if applicable) before performance of any study-specific procedures or tests

You may not qualify if:

• History of cardiac disease:
• Active coronary artery disease, defined as myocardial infarction, unstable angina, coronary bypass graft, or stenting within 6 months prior to study entry
• Evidence of uncontrolled bradycardia or other cardiac arrhythmia defined as greater than or equal to Grade 2 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4, or uncontrolled hypertension
• Any of the following ECG findings: PR interval greater than 240 msec or less than or equal to 110 msec or bradycardia defined as sinus rate \<50 beats per minute
• Mean QTcF interval greater than 450 msec on triplicate centrally read Screening ECGs
• Cardiac conduction abnormalities denoted by any of the following: evidence of second-degree (type II) or third-degree atrioventricular block, evidence of ventricular pre-excitation, ECG evidence of complete left bundle branch block, intraventricular conduction delay with QRS duration greater than 120 msec, atrial fibrillation, or presence of cardiac pacemaker
• Personal or family history of long-QT syndrome
• Active, clinically serious infections defined as greater than or equal to Grade 2 according to NCI CTCAE, version 4
• Known metastatic brain or meningeal tumors, unless that subject is greater than 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
• Pregnant or breastfeeding
• Any major surgical procedure within 3 weeks prior to the first dose of study drug
• Significant gastrointestinal disorders, in the opinion of the Principal Investigator (eg, Crohn's disease, ulcerative colitis, extensive gastric resection, comorbid disease which causes malabsorption of the drug)
• Received tivantinib as prior therapy
• Received anticancer therapy, including antibody, retinoid, or hormonal treatment (except megestrol acetate as supportive care), and radiation, within 3 weeks before dosing. Prior and concurrent use of hormone replacement therapy, the use of gonadotropin-releasing hormone modulators for prostate cancer, and the use of somatostatin and analogs for neuroendocrine tumors are permitted
• Any other investigational drug within 3 weeks prior to dosing

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Medpace, Inc.: collaborator

Study Sites (1)

START - South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Interventions

ARQ 197

Study Officials

• Hamim Zahir, BPharm, PhD

  Daiichi Sankyo UK Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2012
• First Posted: October 3, 2012
• Study Start: July 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: May 1, 2013
• Last Updated: February 12, 2019

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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.

Locations

US (1)