Clinical trial NCT01624467: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Solid Tumors
Keywords: Advanced Solid Tumors
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-06-20
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Time-Matched Baseline in QT Interval Corrected for Heart Rate (QTc)
timeFrame: 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 outcomes:
measure: Change From Time-Matched Baseline ≥ 25% and Absolute Value of QRS >110 Msec (Electrocardiographic Parameters: QRS Interval)
timeFrame: 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
measure: PR Change From Time-Matched Baseline ≥25% and Absolute Value of PR > 200 Msec (Electrocardiographic Parameters: PR Interval)
timeFrame: 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
measure: Change From Time-Matched Baseline in Heart Rate (HR) (Electrocardiographic Parameters: Heart Rate [HR])
timeFrame: Baseline, Cycle1 Day 36: Pre-infusion, End of Infusion, 1 Hour (hr), 2, 4, 24, 48, 72 hr Post Infusion
measure: Pharmacokinetics (PK): Area Under the Concentration-Time Curve of Necitumumab From Zero to Infinity (AUC[0-∞])
timeFrame: Cycle1 (Days 1 and 36): Pre-infusion, 50 minutes, 1.5, 2.5, 4.5, 24, 28, 72, and 168 hours
measure: Pharmacokinetics: Maximum Drug Concentration (Cmax) of Necitumumab
timeFrame: Cycle 1 (Days 1 and 36); Pre-infusion, 50 minutes, 1.5, 2.5, 4.5, 24, 28, 72, and 168 hours
measure: 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])
timeFrame: Baseline to Measured Progressive Disease (up to 21 Months)
measure: Number of Participants With an Incidence of Anti-Necitumumab Antibodies
timeFrame: Baseline to Post Infusion 30 Day Follow-up
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Michigan
city: Detroit
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Michigan
city: Las Vegas
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Nevada
city: New Brunswick
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: New Jersey
city: Huntersville
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: North Carolina
city: Cleveland
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Ohio
city: Pittsburgh
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Pennsylvania
city: Salt Lake City
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Utah
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: