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

This study has been completed.
Sponsor:
Collaborator:
ImClone LLC
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00698841
First received: June 16, 2008
Last updated: May 10, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Advanced Cancer
Drug: Cetuximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With Clinically Meaningful Prolongation of the QT Interval Corrected for Heart Rate (QTc) From Time-matched Baseline [ Time Frame: Baseline, Day 1, and then weekly to end of Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
    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.

  • Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point [ Time Frame: Predose Day 1 (Baseline) to end of Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Clinically Significant Changes in PR Interval, QRS Interval, and Heart Rate [ Time Frame: Baseline, Day 1, and then weekly to end of Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: Baseline through Cycle 1 (28 days), continuously ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade [ Time Frame: Baseline through Cycle 1 (28 days), continuously ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study [ Time Frame: At screening, at the end of Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
    BL=baseline; OS=on-study; ULN=upper level of normal. Albumin,low (g/dL) Grade 1:<LLN-30, Grade 2:<30-20, Grades 3&4:<20. Aspartate aminotransferase (AST)(U/L) Grade 1:>ULN-2.5*ULN, Grade 2:>2.5-5.0*ULN, Grade 3:>5.0-20.0*ULN, Grade 4:>20.0*ULN. Total bilirubin, high Grade 1:ULN-1.5*ULN, Grade 2:>1.5-3.0*ULN, Grade 3:>3.0-10.0*ULN, Grade 4:>10.0*ULN. Alkaline phosphatase (ALP) (U/L) Grade 1:>ULN-2.5*ULN, Grade 2:>2.5-5.0*ULN, Grade 3:>5.0-20.0*ULN, Grade 4:>20.0*ULN. Creatinine (mg/dL) Grade 1:>ULN-1.5*ULN, Grade 2:>1.5-3.0*ULN, Grade 3:>3.0-6.0*ULN, Grade 4:>6.0*ULN.

  • Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) [ Time Frame: At screening, at the end of Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
    BL=baseline; OS=on-study; LLN=lower level of normal; ULN=upper level of normal. Sodium, low(mmol/L) Grades 1&2:<LLN-130, Grade 3:<130-120, Grade 4:<120. Sodium, high (mmol/L) Grade 1:>ULN-150, Grade 2:>150-155, Grade 3:>155-160, Grade 4:>160. Potassium, high (mmol/L) Grade 1:>ULN-5.5, Grade 2:>5.5-6.0, Grade 3:>6.0-7.0, Grade 4:>7.0. Glucose, low(mg/dL) Grade 1:<LLN-55, Grade 2:<55-40, Grade 3:<40-30, Grade 4:<30. Glucose, high (mg/dL) Grade 1:>ULN-160, Grade 2:>160-250, Grade 3:>250-500, Grade 4:>500. Calcium, high(mg/dL) Grade 1:>ULN-11.5, Grade 2:>11.5-12.5, Grade 3:>12.5-13.5, Grade 4:>13.

  • Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study [ Time Frame: At screening, weekly prior to start of cetuximab infusion, at end of Cycle 1 (28 days), and at 30-day follow-up ] [ Designated as safety issue: Yes ]
    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:<LLN to 10.0, Grade 2:<10.0 to 8.0, Grade 3:<8.0 to 6.5, Grade 4:<6.5. Platelets Grade 1:LLN to 75.0*10^9/L, Grade 2:<75.0 to 50.0*10^9/L, Grade 3:<50.0 to 25.0*10^9/L, Grade 4:<25.0 to 10^9/L. White blood cells Grade 1:<LLN to 3.0*10^9/L, Grade 2:<3.0 to 2.0*10^9/L, Grade 3:<2.0 to 1.0*10^9/L, Grade 4:<1.0*10^9/L. Neutrophils Grade 1:<LLN to 1.5*10^9/L, Grade 2:<1.5 to 1.0*10^9/L, Grade 3:<1.0 to 0.5*10^9/L, Grade 4:<0.5*10^9/L.


Enrollment: 79
Study Start Date: February 2009
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab 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.
Other Name: Erbitux

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00698841

Locations
United States, Alabama
Northwest Alabama Cancer Center
Muscle Shoals, Alabama, United States, 35661
United States, Arizona
Donald W. Hill, MD
Casa Grande, Arizona, United States, 85222
United States, California
Compassionate Cancer Care Medical Group, Inc
Corona, California, United States, 92879
Compassionate Cancer Care Medical Group Inc
Fountain Valley, California, United States, 92708
Pacific Shores Medical Group
Long Beach, California, United States, 90813
Desert Hospital Comprehensive Cancer Center
Palm Springs, California, United States, 92262
Compassionate Cancer Care Medical Group, Inc
Riverside, California, United States, 92501
American Institute Research
Whittier, California, United States, 90603
United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Florida
Baptist Cancer Institute
Jacksonville, Florida, United States, 32207
Ocala Oncology Center
Ocala, Florida, United States, 34471
United States, Louisiana
Brinz, Burroff, Gurtler, & Russo
Metairie, Louisiana, United States, 70006
United States, Oklahoma
Cancer Specialists Of Oklahoma
Oklahoma City, Oklahoma, United States, 73112
United States, Rhode Island
Pharma Resource
East Providence, Rhode Island, United States, 02915
United States, Texas
Austin Cancer Centers
Austin, Texas, United States, 78759
Puerto Rico
Local Institution
San Juan, Puerto Rico, 00910
Sponsors and Collaborators
Bristol-Myers Squibb
ImClone LLC
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00698841     History of Changes
Other Study ID Numbers: CA225-315
Study First Received: June 16, 2008
Results First Received: April 14, 2011
Last Updated: May 10, 2011
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Canada: Ethics Review Committee

Additional relevant MeSH terms:
Neoplasms
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014