A Drug-Interaction Study of Necitumumab (IMC-11F8) in Com... | NCT01606748

NCT01606748

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
CP11-1115	Other Identifier	ImClone Systems
I4X-IE-JFCJ	Other Identifier	Eli Lilly and Company

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Necitumumab, Gemcitabine and Cisplatin	Experimental	The study will be conducted in two sequential periods: a 3-week PK run-in participants will be treated sequentially with single doses of cisplatin, gemcitabine, and necitumumab. Cycle 1 will begin immediately following the PK run-in period.	Biological: Necitumumab Drug: Gemcitabine Drug: Cisplatin

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Necitumumab	Biological	PK Run-In Period: Necitumumab administered on Day 3 of the 3-week PK run-in period as an intravenous (I.V.) infusion at an absolute dose of 800 mg Treatment Cycles: Necitumumab administered on Days 1 and 8 of every 3-week cycle as an intravenous (I.V.) infusion at an absolute dose of 800 mg Participants in Cohort 1 will receive necitumumab Process C drug product and participants in Cohort 2 will receive necitumumab Process D drug product

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Necitumumab		Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 Hour (h) Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion
PK: Dose-Normalized Cmax of Gemcitabine		Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion
PK: Dose-Normalized Cmax of Cisplatin		Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion
PK: Area Under Concentration-Time Curve From Zero to Time 168 (AUC[-168]) of Necitumumab		Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion
PK: Dose-Normalized AUC(0-24) of Gemcitabine		Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion
PK: Dose-Normalized AUC(0-5) of Cisplatin		Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion
PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity, (AUC[0-∞]) of Necitumumab		Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1 Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Anti-Necitumumab Antibodies	A participant was considered to have an anti-necitumumab antibody response if anti-drug antibodies (ADA) were confirmed positive. Treatment emergent antibodies were defined as any anti-necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer.	Baseline through, 30-Day Follow-Up

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have documented advanced or metastatic malignant solid tumors (except for colorectal tumors with KRAS mutation) that are resistant 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 (other than alopecia) 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, hematologic and renal function
If female, are surgically sterile, postmenopausal, or agree to be compliant with a highly effective contraceptive method during and for 6 months after the treatment period. If male, are surgically sterile or agree to be compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period
Female participants of childbearing potential have a negative serum pregnancy test within 7 days prior to the first dose of study therapy

Exclusion Criteria:

Have received a systemic anticancer agent (including EGFR tyrosine kinase inhibitors) or device within 28 days prior to first dose of study therapy
The most recent anticancer therapy received by the participant included either gemcitabine or cisplatin (or both)
Have received radiotherapy within 14 days prior to first dose of study therapy
Have received cytotoxic chemotherapy within 21 days prior to first dose of study therapy
Are receiving concurrent treatment with another anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiation therapy, chemoembolization, or targeted therapy
Are considered surgical candidates (with resectable disease)
Have brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants
Have narrowing of or blockage in large veins
Have coronary artery disease or uncontrolled congestive heart failure
Have uncontrolled angina pectoris, or experienced myocardial infarction within 6 months prior to first dose of study therapy
Have an ongoing or active infection (requiring treatment), including active tuberculosis or known infection with the human immunodeficiency virus
Have a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder
Have known drug or alcohol abuse
If female, are pregnant or breastfeeding
Have had major surgery within 28 days prior to first dose of study medication or subcutaneous venous access device implantation within 7 days prior to first dose of study therapy
Are currently enrolled in, or discontinued within the 30 days prior to first dose of study therapy from a clinical trial involving an investigational product or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

Name	Affiliation	Role
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	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
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.		Scottsdale	Arizona	85258

IPD Sharing Statement Module

Arm/Group Information

ID	Title	Description
FG000	Necitumumab Cohort 1	Necitumumab administered on Day 3 of the 3-week PK run-in period as an intravenous (IV) infusion at an absolute dose of 800 milligrams (mg). Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/square meter (m2). Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2.
FG001	Necitumumab Cohort 2	Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 2 received necitumumab drug product manufactured using a new and comparable necitumumab drug substance (Process D drug product). Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Necitumumab Cohort 1	Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product and participants in Cohort 2 received necitumumab Process D drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Necitumumab

All participants who received at least one dose of study drug and had evaluable data for PK.

Posted

Geometric Mean

Geometric Coefficient of Variation

microgram/milliliter (ug/mL)

Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 Hour (h) Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion

ID	Title	Description
OG000	Necitumumab Cohort 1 Day 3 Run-in	Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product.
OG001	Necitumumab Cohort 1 Day 1, Cycle 1, Combination

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Necitumumab Cohort 1	Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg. Participants in Cohort 1 received necitumumab Process C drug product and participants in Cohort 2 received necitumumab Process D drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2. Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an IV infusion at a dose of 1250 mg/m2.

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
D001943	Breast Neoplasms

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms

ID	Term
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides