Study to Evaluate the Effect of Cetuximab on Corrected QT (QTc) Interval Changes in Patients With Advanced Malignancies From Solid Tumors

Advanced Cancer Clinical Trial

Official title:

A Study to Evaluate the Relationship Between Cetuximab Therapy and Corrected QT (QTc) Interval Changes in Patients With Advanced Malignancies From Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00698841
• Other study ID #: CA225-315
• Status: Completed
• Phase: Phase 2
• First received: June 16, 2008
• Last updated: November 24, 2015
• Start date: February 2009
• Est. completion date: February 2010

Study information

• Verified date: November 2015
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaCanada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether corrected QT (QTc) interval changes occur on an electrocardiogram (ECG) when cetuximab is administered to the study population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Advanced or metastatic malignant disease originating from solid tumors

• Adequate recovery from previous therapy or intervention; at least 21 days since major surgery or prior radiation therapy

• Measurable or evaluable disease

Exclusion criteria:

• Women of childbearing potential (WOCBP) who are breastfeeding, pregnant, or unwilling or unable to use acceptable contraception during the study and for at least 12 weeks after the last on-study dose of cetuximab

• Men unwilling to use acceptable contraception during the study if engaged in sexual relations with a WOCBP

• Symptomatic brain metastasis

• History of myocardial infarction 6 months or less prior to study entry, of severe congestive heart failure, of uncontrolled angina, or of uncontrolled arrhythmias

• Clinically relevant abnormality on screening electrocardiogram (ECG), preventing an accurate measurement of the QT interval

• Congenital long QT syndrome

• History of risk factors for ventricular tachycardia or Torsades de pointes or history of fainting, unexplained loss of consciousness, or convulsions

• Prolonged QTc interval on screening ECG (greater than 470 msec) using Fridericia's correction formula

• Heart rate slower than 50 bpm or faster than 100 bpm at rest during screening ECG measurements

• Implantable pacemaker or automatic implantable cardioverter defibrillator

• Sustained supine systolic blood pressure higher than 150 mmHg or lower than 90 mmHg or a diastolic blood pressure lower than 45 mmHg or higher than 95 mmHg at screening

• Known history of arterial thrombotic events within 6 months prior to study initiation

• Known history of significant peripheral artery disease

• Current participation in a clinical trial with another investigational new drug or device

• Receipt of an investigational new drug or device within 21 days prior to enrollment in this study

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Cancer

Intervention

Drug:
• Cetuximab
Cetuximab administered by intravenous (IV) infusion at an initial dose of 400 mg/m^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m^2 over 60 minutes.

Locations

Country	Name	City	State
Puerto Rico	Local Institution	San Juan
United States	Austin Cancer Centers	Austin	Texas
United States	Donald W. Hill, MD	Casa Grande	Arizona
United States	Compassionate Cancer Care Medical Group, Inc	Corona	California
United States	Pharma Resource	East Providence	Rhode Island
United States	Compassionate Cancer Care Medical Group Inc	Fountain Valley	California
United States	Baptist Cancer Institute	Jacksonville	Florida
United States	Pacific Shores Medical Group	Long Beach	California
United States	Brinz, Burroff, Gurtler, & Russo	Metairie	Louisiana
United States	Northwest Alabama Cancer Center	Muscle Shoals	Alabama
United States	Ocala Oncology Center	Ocala	Florida
United States	Cancer Specialists Of Oklahoma	Oklahoma City	Oklahoma
United States	Desert Hospital Comprehensive Cancer Center	Palm Springs	California
United States	Compassionate Cancer Care Medical Group, Inc	Riverside	California
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	American Institute Research	Whittier	California

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	ImClone LLC

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Clinically Meaningful Prolongation of the QT Interval Corrected for Heart Rate (QTc) From Time-matched Baseline	12-Lead continuous digital electrocardiogram (ECG) data were collected at preselected time points at baseline visit and on Days 1, 8, 15, 22, and 29. The QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. The corrected QTc is the QT interval corrected for heart rate. Prolongation of the QTc was identified as clinically meaningful at the investigator's discretion.	Baseline, Day 1, and then weekly to end of Cycle 1 (28 days)	Yes
Primary	Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point	The QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. The QTc is the QT interval corrected for heart rate. The QTcF=QT/RR^1/3, where RR=RR interval in seconds. Baseline=predose. Mean change in QTc interval from baseline to time t=QTc interval at time t minus QTc interval at baseline.	Predose Day 1 (Baseline) to end of Cycle 1 (28 days)	Yes
Secondary	Number of Participants With Clinically Significant Changes in PR Interval, QRS Interval, and Heart Rate	12-Lead continuous digital ECG data were collected at preselected time points at baseline visit and on Days 1, 8, 15, 22, and 29. The PR interval is the time from the onset of the P wave to the beginning of the QRS complex. The QRS interval=deflections in the ECG, comprising Q, R, and S waves, that represent depolarization of the ventricles. Clinically significant was determined at the investigator's discretion.	Baseline, Day 1, and then weekly to end of Cycle 1 (28 days)	Yes
Secondary	Number of Participants With Death, Treatment-related Death, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs) Leading to Discontinuation, and Treatment-related AEs Leading to Discontinuation	AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, or is an important medical event. Treatment related=possibly, probably, or certainly related to or of unknown relationship to study treatment.	Baseline through Cycle 1 (28 days), continuously	Yes
Secondary	Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade	AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. AEs of special interest have been sponsor-selected based on the known clinical effects of cetuximab. Treatment related=possibly, probably, or certainly related to or of unknown relationship to study treatment. CTC Grade 1: Mild. Grade 2: Moderate. Grade 3: Severe or medically significant but not immediately life-threatening. Grade 4: Life-threatening.	Baseline through Cycle 1 (28 days), continuously	Yes
Secondary	Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study	BL=baseline; OS=on-study; ULN=upper level of normal. Albumin,low (g/dL) Grade 1:	At screening, at the end of Cycle 1 (28 days)	Yes
Secondary	Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued)	BL=baseline; OS=on-study; LLN=lower level of normal; ULN=upper level of normal. Sodium, low(mmol/L) Grades 1&2:	At screening, at the end of Cycle 1 (28 days)	Yes
Secondary	Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study	BL=baseline; OS=on-study; LLN=lower level of normal. Laboratory values assessed using CTC for AEs, Version 3.0. Hemoglobin (g/dL) Grade 1:	At screening, weekly prior to start of cetuximab infusion, at end of Cycle 1 (28 days), and at 30-day follow-up	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form