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Solid TumorsPhase 1NCT01699061

Effect of Tivantinib on the QTC Interval in Cancer Subjects

A Phase 1 study testing Tivantinib in people with Solid Tumors, run by Daiichi Sankyo at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors
What is being tested?
Tivantinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
38 participants
Where
1 siteUnited States
Study dates
Jul 2012to May 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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
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  • 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
  • Substance abuse or medical, psychological, or social conditions that may, in the opinion of the Investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results
  • Any condition that is unstable or that could jeopardize the safety of the subject and the subject's protocol compliance, including known infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus
  • Inability to swallow oral medications that could interfere with the absorption of tivantinib
  • Administration or possibility of initiating or continuing any treatment with any known CYP 3A4 and CYP2C19 enzyme and P-glycoprotein altering drugs (inducer or inhibitor) or non-drug agents or gastric pH modifiers within the 14 days prior to dosing and/or during the PK evaluation (14 to 15 days) after initiation of the study treatment
  • Subjects with a clinical diagnosis of hepatic impairment and/or hepatocellular carcinoma and/or chronic liver cirrhosis with confirmation either by previous biopsy or with findings on ultrasound, computed tomography (CT) or MRI consistent with chronic liver cirrhosis
  • Subjects who are on treatment receiving drugs that may affect QTc (eg, quinidine or moxifloxacin)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • START - South Texas Accelerated Research Therapeutics, LLC

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: A PHASE 1 SINGLE-BLIND, SINGLE-SEQUENCE STUDY ASSESSING THE EFFECT OF TIVANTINIB ON THE QTC INTERVAL IN CANCER SUBJECTS

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

Read the detailed description

The study is designed to estimate the maximum change in QTcF (change from baseline) between placebo and multiple-dose tivantinib. A tivantinib oral dose of 360 mg BID has been selected for this study because this is the highest dose currently being evaluated in clinical studies.

Conditions
Solid Tumors
Being tested
Tivantinib, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TivantinibDrug

    Also called ARQ 197

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

  • PlaceboDrug

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

Study groups in NCT01699061
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo tablet administered with a meal twice a day on Day 1
Receives: Drug: Placebo
TivantinibExperimental3 tivantinib tablets 120 mg administered twice daily with a meal starting on Day 2
Receives: Drug: Tivantinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

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

Secondary outcomes (3)

  1. 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

    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)

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

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

    Blood samples for PK analysis will be obtained within 15 minutes following each pre-specified ECG measurement

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

  3. Explore the tivantinib plasma concentration-QTc interval relationship

    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). Blood samples for PK analysis will be obtained within 15 minutes following each pre-specified ECG measurement. The relationship between plasma concentrations of tivantinib and the change from baseline in QTc will be quantified using a linear random coefficient regression model approach.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Oct 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionJan 2013
  4. Study completionMay 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
Single blind
Who is masked
Participant
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01699061
Sponsor's protocol ID
ARQ197-A-U159
Status last verified
Feb 2018
First submitted
1 Oct 2012
Last updated
12 Feb 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: 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/

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tivantinib in people with Solid Tumors, run by Daiichi Sankyo at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The time-matched difference in the QTcF interval at each timepoint after both single and multiple doses of tivantinib compared with placebo (time frame: Baseline and 1, 2, 3, 4, 6, 8, and 12 hours post dose on Days 1, 2, and 5 (+3 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01699061.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2019.

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