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

Study Overview
=================
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.

Official Title
-----------------
A Study to Determine Whether Necitumumab (IMC-11F8) Monotherapy Affects the Corrected QT (QTc) Interval in Patients With Advanced Solid Tumors

Conditions
-----------------
Solid Tumors

Intervention / Treatment
-----------------
* Biological: Necitumumab


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Necitumumab<br>800 mg necitumumab, administered once per week as an intravenous infusion (IV) | Biological: Necitumumab<br>* 800 mg necitumumab, administered once per week IV<br>* Other names: LY3012211;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Time-Matched Baseline in QT Interval Corrected for Heart Rate (QTc) | 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 | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Time-Matched Baseline ≥ 25% and Absolute Value of QRS >110 Msec (Electrocardiographic Parameters: QRS Interval) |  | 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) |  | 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]) | Change in HR from time-matched measures performed at baseline. | Baseline, Cycle1 Day 36: Pre-infusion, End of Infusion, 1 Hour (hr), 2, 4, 24, 48, 72 hr Post Infusion | 
| Pharmacokinetics (PK): Area Under the Concentration-Time Curve of Necitumumab From Zero to Infinity (AUC[0-∞]) |  | 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 |  | 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]) | 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. | Baseline to Measured Progressive Disease (up to 21 Months) | 
| Number of Participants With an Incidence of Anti-Necitumumab Antibodies |  | Baseline to Post Infusion 30 Day Follow-up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced Solid Tumors