Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Oxaliplatin

Leucovorin

Fluorouracil

Antibodies

Antibodies, Monoclonal

Levoleucovorin

Folic Acid

Immunoglobulins

Necitumumab

Vitamin B Complex

Antidotes

Protective Agents

Trace Elements

Antineoplastic Agents, Immunological

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

Participants will receive IMC-11F8 (necitumumab) once every 2 weeks in combination with the mFOLFOX-6 regimen (oxaliplatin/5-FU/FA)

IMC-11F8 800 milligrams (mg) intravenous (IV) infusion over 50 minutes on Day 1

IMC-11F8 (necitumumab)

Oxaliplatin 85 milligrams per meter square (mg/m²) IV infusion over 2 hours on Day 1

FA 400 mg/m² IV infusion bolus injection

Folinic acid (FA)

5-FU 400 mg/m² as a bolus followed by 2400 mg/m² IV continuous infusion over 46 hours

5-FU

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)

The purpose of this study is to determine if IMC-11F8 in combination with chemotherapy is effective in treating colorectal cancer (CRC).

The purpose of this study is to evaluate the anti-tumor activity (best overall response) of the anti-epidermal growth factor receptor (EGFR) monoclonal antibody IMC-11F8 administered in combination with mFOLFOX-6 chemotherapy regimen in treatment-naive, locally-advanced or metastatic CRC participants.

Study of IMC-11F8 in Participants With Colorectal Cancer

Open Label, Multicenter, Phase II Study Evaluating the Efficacy and Safety of IMC-11F8 in Combination With 5-FU/FA and Oxaliplatin (mFOLFOX-6) in Patients With Treatment-naïve, Locally-advanced or Metastatic Colorectal Cancer

CR and PR defined using Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.0 criteria. CR was defined as the disappearance of all target and non-target lesions and 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. 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.

OS was defined as the duration from the date of first dose to the date of death from any cause. OS was estimated by the Kaplan-Meier method. Participants who were alive at the time of the data inclusion cutoff or lost to follow-up, OS was censored at the last contact.

PFS was defined as the time from date of first dose to the first observation of disease progression or death due to any cause. Progressive disease (PD) was determined using RECIST v1.0 criteria. PD was defined as ≥20% increase in the sum of LD of target lesions, taking as reference the smallest sum of the LD recorded since treatment started or the appearance of new lesions and/or unequivocal progression of existing nontarget lesions. PFS was estimated by the Kaplan-Meier method. Participants who had no PD or death at the time of the data inclusion cutoff, PFS was censored at their last tumor assessment prior to the earliest of the following events: 2 or more missed visits, additional cancer treatment or the end of the follow-up period.

The number of participants who experienced AEs, SAEs or death during the study and within 30 days of last dose. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

The duration of response was defined as the time from first confirmed CR or PR to the first time of PD or death due to any cause. CR, PR and PD were defined using RECIST v1.0 criteria. CR was defined as the disappearance of all target and non-target lesions; PR was defined as a ≥30% decrease in the sum of the LD of the target lesions, taking as reference the baseline sum of the LD; PD was defined as a ≥20% increase in the sum of LD of target lesions, taking as reference the smallest sum of the LD recorded since treatment started or the appearance of new lesions and/or unequivocal progression of existing nontarget lesions. Participants with CR or PR who had no PD or death at the time of the data inclusion cutoff, the duration of response was censored at their last contact.

A participant was considered to have an anti-IMC-11F8 response if there were 2 consecutive positive samples or if the final sample tested is positive. Participants with a baseline sample positive for anti-IMC-11F8 antibodies were considered unevaluable for immunogenicity. A sample was considered positive for IMC-11F8 antibodies if it exhibited a post-baseline treatment emergent antibody level that exceeded the upper 95% confidence interval of the mean determined from the normal anti-IMC 11F8 level found in healthy treatment-naïve individuals.

The t1/2 is the time measured for the plasma concentration of the drug to decrease by one half.

CL is the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time.

Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug at steady-state.

Tumor tissues collected prior to study drug administration were evaluated for the presence or absence of KRAS mutations by a retrospective analysis.

Eli Lilly and Company

On Day 1 of each 2-week cycle, each participant received IMC-11F8 (necitumumab) in combination with the mFOLFOX-6 regimen (oxaliplatin/5-FU/FA) in the order shown:

* 800 mg IMC-11F8 IV infusion over 50 minutes;
* 85 mg/m² oxaliplatin IV infusion over 2 hours;
* 400 mg/m² folinic acid;
* 400 mg/m² 5-FU as an IV bolus injection; and immediately followed by
* A 46-hour continuous IV infusion of 5-FU at 2400 mg/m². All treatments were administered every 2 weeks until disease progression, the development of unacceptable toxicity, noncompliance, withdrawal of consent, investigator decision, or until other criteria for treatment discontinuation were met.

IMC-11F8 (Necitumumab) + mFOLFOX-6

On Day 1 of each 2-week cycle, each participant received IMC-11F8 (necitumumab) in combination with the mFOLFOX-6 regimen (oxaliplatin/5-FU/FA) in the order shown:

* 800 mg IMC-11F8 IV infusion over 50 minutes
* 85 mg/m² oxaliplatin IV infusion over 2 hours
* 400 mg/m² folinic acid
* 400 mg/m² 5-FU as an IV bolus injection; and immediately followed by
* A 46-hour continuous IV infusion of 5-FU at 2400 mg/m² All treatments were administered every 2 weeks until disease progression, the development of unacceptable toxicity, noncompliance, withdrawal of consent, investigator decision, or until other criteria for treatment discontinuation were met.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Belgium

Spain

Region of Enrollment

All enrolled participants who received any quantity of study drug.

Chief Medical Officer

Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response )

All enrolled participants who received any quantity of study drug. Participants censored =14.

Overall Survival (OS)

All enrolled participants who received any quantity of study drug. Participants censored =13.

Progression-Free Survival (PFS)

SAEs

Deaths

Number of Participants With Adverse Events (AEs), Serious AEs (SAEs) or Death

All enrolled participants who received any quantity of study drug and had confirmed CR or PR. Participants censored =2.

Duration of Response

All participants who received any amount of study drug and were IMC-11F8 antibody negative at baseline.

Serum Anti-IMC-11F8 Antibody Assessment (Immunogenicity)

On Day 1 of Cycle 1, each participant received IMC-11F8 (necitumumab) in combination with the mFOLFOX-6 regimen (oxaliplatin/5-FU/FA) in the order shown:

* 800 mg IMC-11F8 IV infusion over 50 minutes;
* 85 mg/m² oxaliplatin IV infusion over 2 hours;
* 400 mg/m² folinic acid;
* 400 mg/m² 5-FU as an IV bolus injection; and immediately followed by
* A 46-hour continuous IV infusion of 5-FU at 2400 mg/m². All treatments were administered every 2 weeks until disease progression, the development of unacceptable toxicity, noncompliance, withdrawal of consent, investigator decision or until other criteria for treatment discontinuation were met.

All enrolled participants who received any quantity of study drug and had pharmacokinetic (PK) data available to calculate Cmax.

Maximum Concentration (Cmax) of IMC-11F8 at Study Day 1 of Cycle 1

All enrolled participants who received any quantity of study drug and had PK data available to calculate AUC(0-∞).

Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)] of IMC-11F8 at Study Day 1 of Cycle 1

All enrolled participants who received any quantity of study drug and had PK data available to calculate t1/2.

Half-Life (t1/2) of IMC-11F8 at Study Day 1 of Cycle 1

All enrolled participants who received any quantity of study drug and had PK data available to calculate CL.

Clearance (CL) of IMC-11F8 at Study Day 1 of Cycle 1

All enrolled participants who received any quantity of study drug and had PK data available to calculate Vss.

Volume of Distribution (Vss) of IMC-11F8 at Study Day 1 of Cycle 1

Zero participants were analyzed, Cmax results were not collected.

Cmax at Study Day 1 of Cycles 2 Through 6

Zero participants were analyzed, AUC results were not collected.

Area Under the Curve (AUC) at Study Day 1 of Cycles 2 Through 6

Zero participants were analyzed, t1/2 results were not collected.

t1/2 at Study Day 1 of Cycles 2 Through 6

Zero participants were analyzed, CL results were not collected.

CL at Study Day 1 of Cycles 2 Through 6

Zero participants were analyzed, Vss results were not collected.

Vss at Study Day 1 of Cycles 2 Through 6

Zero participants were analyzed, the outcome measure was registered in error.

Change From Baseline in Tumor Size

KRAS Mutation Positive

KRAS Mutation Negative

All enrolled participants who had assessment of tumor tissue samples at baseline.

Kirsten Rat Sarcoma (KRAS) Mutation Status

On Day 1 of each 2-week cycle, each participant received IMC-11F8 (necitumumab) in combination with the mFOLFOX-6 regimen (oxaliplatin/5-FU/FA) in the order shown:

* 800 milligrams (mg) IMC-11F8 intravenous (IV) infusion over 50 minutes
* 85 milligrams per meter square (mg/m²) oxaliplatin IV infusion over 2 hours
* 400 mg/m² folinic acid
* 400 mg/m² 5-FU as an IV bolus injection; and immediately followed by
* A 46-hour continuous IV infusion of 5-FU at 2400 mg/m² All treatments were administered every 2 weeks until disease progression, the development of unacceptable toxicity, noncompliance, withdrawal of consent or until other criteria for treatment discontinuation were met.

Spots Global Cancer Trial Database for Study of IMC-11F8 in Participants With Colorectal Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial