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

• ClinicalTrials.gov Identifier: NCT00698841
• Recruitment Status: Completed
• First Posted: June 17, 2008
• Results First Posted: May 11, 2011
• Last Update Posted: December 24, 2015
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Advanced Cancer	Drug: Cetuximab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 79 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: February 2009
• Actual Primary Completion Date: February 2010
• Actual Study Completion Date: February 2010

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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) ]
   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.
2. 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) ]
   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 :

1. 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) ]
   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.
2. 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 ]
   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.
3. Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade [ Time Frame: Baseline through Cycle 1 (28 days), continuously ]
   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.
4. 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) ]
   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.
5. 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) ]
   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.
6. 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 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Deeken JF, Shimkus B, Liem A, Hill D, Gurtler J, Berghorn E, Townes L, Lu H, Trifan O, Zhang S. Evaluation of the relationship between cetuximab therapy and corrected QT interval changes in patients with advanced malignancies from solid tumors. Cancer Chemother Pharmacol. 2013 Jun;71(6):1473-83. doi: 10.1007/s00280-013-2146-5. Epub 2013 Apr 16.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00698841
• Other Study ID Numbers: CA225-315
• First Posted: June 17, 2008
• Results First Posted: May 11, 2011
• Last Update Posted: December 24, 2015
• Last Verified: November 2015

Additional relevant MeSH terms:

Neoplasms; Cetuximab; Antineoplastic Agents, Immunological; Antineoplastic Agents