A Cardiac Safety Study of Tivozanib to Evaluate the Electrocardiogram and Pharmacokinetic-Electrocardiogram Dynamics in Subjects With Advanced Solid Tumors

NCT01210846 | Completed Phase 1

• 1 other identifier: AV-951-10-112
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to obtain QTc data, to assess the effects of tivozanib on ECG morphology, and to determine the pharmacokinetic pharmacodynamic (PK-PD) relationship between any observed changes in cardiac repolarization (defined by QTcF duration) and the serum concentration of tivozanib.

Conditions

Advanced Solid Tumors

Keywords

AV-951; tivozanib; QTc; advanced solid tumors; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Change from baseline in QTcF

  22 days

Secondary Outcomes (7)

• Change from baseline in QTc with Bazett correction method (QTcB)

  22 days

• Change from baseline in heart rate (HR)

  22 days

• Change from baseline in PR interval

  22 days

• Change from baseline in QRS interval

  22 days

• Change from baseline in Uncorrected QT interval

  22 days

Study Arms (1)

tivozanib

EXPERIMENTAL

Drug: tivozanib

Interventions

tivozanib DRUG

1 x 1.5 mg capsule of tivozanib orally once daily for 21 days

tivozanib

Eligibility Criteria

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

You may qualify if:

• Males or females, ≥18 years of age;
• Diagnosis of an advanced solid tumor malignancy with histological or cytological evidence;
• Advanced malignancy, metastatic or unresectable, that has recurred or progressed following standard therapy or failed standard therapy; or for which no standard therapy currently exists; or for which subject is not a candidate, or is unwilling to undergo standard therapy;
• Tumor is not currently amenable to curative surgical intervention;
• Recovery from the effects of any prior surgery, radiotherapy, or systemic antineoplastic therapy;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and life expectancy ≥ 3 months;
• Well controlled thyroid function, in the opinion of the Investigator;
• Able to comprehend and willing to sign an Informed Consent Form (ICF) and able to adhere to dose and visit schedule.

You may not qualify if:

• \- Women who are breast-feeding, pregnant, or intend to become pregnant;
• Primary central nervous system (CNS) malignancies or CNS metastases; subjects with previously treated brain metastasis will be allowed if the brain metastasis have been stable without steroid treatment for at least 3 months following prior treatment (radiotherapy or surgery);
• Clinically significant cardiac disease (New York Heart Association class \> 2) including unstable angina, acute myocardial infarction within 6 months of Day 1, congestive heart failure, or arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities, per Investigator judgment;
• Uncontrolled hypertension: systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg on 2 or more antihypertensive medications, documented on 2 consecutive measurements taken at least 24 hours apart;
• Baseline ECG, QTcF \> 480 ms. If the screening QTcF is \> 480 ms, this may be repeated once and if the QTcF is ≤ 480 ms the subject can be enrolled;
• Any of the following hematologic abnormalities:
• hemoglobin \< 9.0 g/dL;
• Absolute neutrophil count \< 1500 per mm3;
• platelet count \< 100,000 per mm3;
• INR \> 1.5 x upper limit of normal (ULN);
• Any of the following serum chemistry or urine abnormalities:
• total bilirubin \> 1.5 × ULN (or \> 2.5 × ULN for subjects with Gilbert's syndrome);
• AST or ALT \> 2.5 × ULN (or \> 5 × ULN for subjects with liver metastasis);
• alkaline phosphatase \> 2.5 × ULN (or \> 5 × ULN for subjects with liver or bone metastasis);
• creatinine \> 2.0 × ULN;

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (8)

TGEN Clinical Research Service at Scottsdale Healthcare

Scottsdale, Arizona, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, United States

Location

Horizon Oncology Research, Inc.

Lafayette, Indiana, United States

Location

Jayne Gurtler MD, Laura Brinz MD, Angelo Russo MD and Janet Burroff MD APMC

Metairie, Louisiana, United States

Location

Associates in Oncology/Hematology

Rockville, Maryland, United States

Location

Oklahoma University Cancer Institute (OUCI)

Oklahoma City, Oklahoma, United States

Location

Tennessee Onocology

Nashville, Tennessee, United States

Location

Multicare Research Institute/Tacoma General Hospital

Tacoma, Washington, United States

Location

MeSH Terms

Interventions

tivozanib

Study Officials

• Dennis Vargo, MD

  AVEO Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2010
• First Posted: September 29, 2010
• Study Start: October 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: July 1, 2011
• Last Updated: September 26, 2011

Record last verified: 2011-09

Locations

US (8)