A Study of Necitumumab Monotherapy and the QT/QTc Interval in Patient With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT01624467
• Recruitment Status: Completed
• First Posted: June 20, 2012
• Results First Posted: January 29, 2016
• Last Update Posted: July 25, 2016
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: May 24, 2012
• First Posted Date: June 20, 2012
• Results First Submitted Date: December 21, 2015
• Results First Posted Date: January 29, 2016
• Last Update Posted Date: July 25, 2016
• Study Start Date: August 2012
• Actual Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 21, 2015)

Change From Time-Matched Baseline in QT Interval Corrected for Heart Rate (QTc) [ Time Frame: Baseline, Cycle1 Day 1, 8,15, 22, 29, and 36: Pre-infusion, End of Infusion, 1 Hour (hr), 2, 4, 24, 48, 72 hr Post Infusion ]

The corrected QT interval was calculated using Fridericia's correction (QTcF) from electrocardiogram (ECG) data. Each participant had triplicate QT intervals measured at each timepoint and the average was calculated for each participant at each timepoint. For each timepoint, a participant's corresponding baseline (Day -1, pretreatment) QTcF interval was subtracted from the average QTcF intervals to create the change from time-matched baseline in the QTcF interval

• Original Primary Outcome Measures (submitted: June 18, 2012): Change from baseline in QT interval corrected for heart rate (QTc) [ Time Frame: Prior to first dose through Cycle 1 (6 weeks) ]

Current Secondary Outcome Measures (submitted: December 21, 2015)

• Change From Time-Matched Baseline ≥ 25% and Absolute Value of QRS >110 Msec (Electrocardiographic Parameters: QRS Interval) [ Time Frame: Baseline, Cycle1 Day 1, 8, 15, 22, 29, 36: Pre-infusion, End of Infusion, 1 Hour (hr), 2, 4, 24, 48, 72 hr Post Infusion ]
• PR Change From Time-Matched Baseline ≥25% and Absolute Value of PR > 200 Msec (Electrocardiographic Parameters: PR Interval) [ Time Frame: Baseline, Cycle1 Day 1, 8, 15, 22, 29, 36: Pre-infusion, End of Infusion, 1 Hour (hr), 2, 4, 24, 48, 72 hr Post Infusion ]
• Change From Time-Matched Baseline in Heart Rate (HR) (Electrocardiographic Parameters: Heart Rate [HR]) [ Time Frame: Baseline, Cycle1 Day 36: Pre-infusion, End of Infusion, 1 Hour (hr), 2, 4, 24, 48, 72 hr Post Infusion ]
  Change in HR from time-matched measures performed at baseline.
• Pharmacokinetics (PK): Area Under the Concentration-Time Curve of Necitumumab From Zero to Infinity (AUC[0-∞]) [ Time Frame: Cycle1 (Days 1 and 36): Pre-infusion, 50 minutes, 1.5, 2.5, 4.5, 24, 28, 72, and 168 hours ]
• Pharmacokinetics: Maximum Drug Concentration (Cmax) of Necitumumab [ Time Frame: Cycle 1 (Days 1 and 36); Pre-infusion, 50 minutes, 1.5, 2.5, 4.5, 24, 28, 72, and 168 hours ]
• Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) (Tumor Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1 [RECIST 1.1]) [ Time Frame: Baseline to Measured Progressive Disease (up to 21 Months) ]
  ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1,CR was defined as the disappearance of all target and non-target lesions. Percentage of participants was calculated as: (total number of participants with CR or PR from start of the treatment until disease progression or recurrence)/total number of participants treated) * 100. PR defined as a >30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD.
• Number of Participants With an Incidence of Anti-Necitumumab Antibodies [ Time Frame: Baseline to Post Infusion 30 Day Follow-up ]

Original Secondary Outcome Measures (submitted: June 18, 2012)

• Electrocardiographic Parameters: QRS Interval [ Time Frame: Prior to first dose through Cycle 4 (24 weeks) ]
• Electrocardiographic Parameters: PR interval [ Time Frame: Prior to first dose through Cycle 4 (24 weeks) ]
• Electrocardiographic Parameters: Heart Rate (HR) [ Time Frame: Prior to first dose through Cycle 4 (24 weeks) ]
• Pharmacokinetics: area under the concentration-time curve of necitumumab [ Time Frame: Cycle 1: Day 1, 8, 15, 22, 29, and 36 and Cycles 2-4: Day 1 ]
• Pharmacokinetics: maximum drug concentration (Cmax) of necitumumab [ Time Frame: Cycle 1: Day 1, 8, 15, 22, 29, and 36 and Cycles 2-4: Day 1 ]
• Tumor response rate per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Prior to first dose, every 6 weeks after first dose of necitumumab, and at end of therapy ]
• Incidence of anti-necitumumab antibodies [ Time Frame: Prior to first dose, every 6 weeks after first dose, and 30 days after last dose of necitumumab ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Necitumumab Monotherapy and the QT/QTc Interval in Patient With Advanced Solid Tumors
• Official Title: A Study to Determine Whether Necitumumab (IMC-11F8) Monotherapy Affects the Corrected QT (QTc) Interval in Patients With Advanced Solid Tumors
• Brief Summary: The purpose of this study is to determine whether treatment with necitumumab monotherapy affects the QT/QTc interval among participants with advanced solid tumors refractory to standard treatment or for which no standard treatment is available.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumors

Intervention

Biological: Necitumumab

800 mg necitumumab, administered once per week IV

Other Names:

• IMC-11F8
• LY3012211

Study Arms

Experimental: Necitumumab

800 mg necitumumab, administered once per week as an intravenous infusion (IV)

Intervention: Biological: Necitumumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 21, 2015): 75
• Original Estimated Enrollment (submitted: June 18, 2012): 50
• Actual Study Completion Date: June 2015
• Actual Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have documented advanced or metastatic malignant solid tumors (except for colorectal tumors with KRAS mutation) that have not responded to standard therapy or for which no standard therapy is available
• May have measurable or non-measurable disease
• Have resolution to Grade 0 or 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE 4.0) of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy
• Have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
• Have adequate hepatic, renal and hematologic function
• Have potassium, magnesium, and calcium within normal limits
• Subjects, if female, are surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method during and for 6 months after the treatment period. If male, participants are surgically sterile or compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period
• Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization

Exclusion Criteria:

• Are currently enrolled in, or discontinued a clinical trial involving an anticancer investigational product, or concurrently enrolled in any other type of medical research
• Had therapeutic radiotherapy within 14 days prior to the first dose of study therapy
• Have received necitumumab or any other monoclonal antibody (mAb) targeting the EGFR (epidermal growth factor receptor) as the most recent prior treatment
• Have documented and/or symptomatic brain or leptomeningeal metastases
• Have a clinically relevant abnormality on the ECG, preventing an accurate measurement of the QT interval
• Have current clinically-relevant coronary artery disease or uncontrolled congestive heart failure
• Have medically uncontrolled angina pectoris, or has experienced myocardial infarction within 6 months prior to the first dose of study therapy
• Have an implantable pacemaker or automatic implantable cardioverter defibrillator
• Have received sotalol within 10 days prior to the first dose of study therapy
• Have a history of risk factors for ventricular tachycardia or Torsades de pointes, history of fainting, unexplained loss of consciousness, or convulsions
• Have a history of heart failure, congestive heart failure, myocardial infarction, cardiomyopathy, hypokalemia, hypoglycemia, or hypomagnesia
• Have any evidence of conduction abnormality (eg, increased QRS complex)
• Have congenital long QT syndrome
• Have a prolonged QTc interval mean on pretreatment ECG
• Have a heart rate < 50 bpm or > 100 bpm at rest
• Are using a medication that is known to prolong the ECG QT interval, or have received a medication known to prolong the ECG QT interval within 14 days prior to first dose of study therapy
• Have a known allergy / history of hypersensitivity reaction to any of the treatment components, including any ingredient used in the formulation of necitumumab, or a known history of severe (Grade 3-4) hypersensitivity reaction to any monoclonal antibody
• Have an ongoing or active infection (requiring treatment), including active tuberculosis or known infection with the human immunodeficiency virus
• If female, are pregnant or breastfeeding
• Have a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01624467
• Other Study ID Numbers: 14472; CP11-1114 ( Other Identifier: ImClone Systems ); I4X-IE-JFCI ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: Eli Lilly and Company
• Verification Date: June 2016