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

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

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Biological: IMC-11F8 (necitumumab); Drug: Oxaliplatin; Drug: Folinic acid (FA); Drug: 5-FU

Detailed Description

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 Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • ImClone Investigational Site
  • Haine Saint-Paul, Belgium, 7100
    • ImClone Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • ImClone Investigational Site
  • Madrid, Spain, 28040
    • ImClone Investigational Site
  • Valencia, Spain, 46010
    • ImClone Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically-confirmed, EGFR-detectable or EGFR-undetectable CRC
• Locally-advanced unresectable or metastatic adenocarcinoma of the colon or rectum
• At least 1 unidimensional-measurable target lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI); target lesion(s) must not lie within an irradiated area
• Age ≥18 years
• Life expectancy of ≥6 months
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 at study entry
• Adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥1.5 x 10^9 liter (L), hemoglobin ≥10 grams per deciliter (g/dL), and platelets ≥100 x 10^9/L
• Adequate hepatic function as defined by a total bilirubin ≤1.5 milligrams per deciliter (mg/dL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN) (or 5.0 x ULN in the case of liver metastases), and alkaline phosphatase (AP) ≤2.5 x ULN (or 5.0 x ULN in the case of liver metastases)
• Adequate renal function as defined by a serum creatinine ≤1.5 x ULN, creatinine clearance ≥ 60 milliliters per minute (mL/min), or serum albumin ≥lower limit of normal (LLN)
• Participant's relevant toxicities/effects of prior therapy [surgery/radiation therapy (RT)] must have recovered to a stable or chronic level
• Participant agrees to use adequate contraception during the study period and for 4 weeks after the last dose of study treatment. Participants must notify the principal investigator if they themselves or their partner becomes pregnant.
• Participant has provided signed Informed Consent

Exclusion Criteria:

• Has received prior systemic chemotherapy for locally-advanced unresectable or metastatic CRC.
• Has received prior radiotherapy to >25% of bone marrow
• Has documented and/or symptomatic brain metastases
• Has participated in clinical studies of non-approved experimental agents or procedures within 12 weeks of study entry
• Has received previous therapy with monoclonal antibodies
• Has received previous therapy with any agent that targets the EGFR
• Has serious concomitant medical conditions including active uncontrolled infection or cardiac disease, which in the opinion of the investigator, could compromise the participant or study.
• On chronic non-topical corticosteroid treatment for >6 months at doses >10 milligrams per day (mg/day) of prednisolone or equivalent before study entry, which in the opinion of the investigator could compromise the participant or the study
• Has a known dihydropyrimidine dehydrogenase deficiency
• Has a known allergy to any of the treatment components
• Has an acute or subacute intestinal occlusion
• Has peripheral neuropathy ≥Grade 2
• Has a history of other malignancies, with the exception of curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix
• If female, is pregnant (confirmed by urine or serum beta human chorionic gonadotropin test) or breast-feeding
• Has received a prior autologous or allogeneic organ or tissue transplantation
• Has interstitial pneumonia or interstitial fibrosis of the lung
• Has pleural effusion or ascites that causes ≥Grade 2 dyspnea
• Has psychological, familial, sociological, or geographical conditions which do not permit adequate study follow-up, compliance with the protocol, or signature of Informed Consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

Biological: IMC-11F8 (necitumumab); IMC-11F8 800 milligrams (mg) intravenous (IV) infusion over 50 minutes on Day 1; Other Names: IMC-11F8; LY3012211; Portrazza®; Necitumumab; Drug: Oxaliplatin; Oxaliplatin 85 milligrams per meter square (mg/m²) IV infusion over 2 hours on Day 1; Drug: Folinic acid (FA); FA 400 mg/m² IV infusion bolus injection; Drug: 5-FU; 5-FU 400 mg/m² as a bolus followed by 2400 mg/m² IV continuous infusion over 46 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response )	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.	Up to 30 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	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.	First dose to date of death from any cause up to 30 months
Progression-Free Survival (PFS)	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.	First dose to measured PD or death up to 30 months
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs) or Death	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.	First dose to end of treatment and 30-day post treatment follow-up up to 31 months
Duration of Response	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.	Time of response to time of measured PD or death up to 30 months
Serum Anti-IMC-11F8 Antibody Assessment (Immunogenicity)	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.	Baseline up to last day of treatment plus 45 days after last treatment (127 weeks)
Maximum Concentration (Cmax) of IMC-11F8 at Study Day 1 of Cycle 1		Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose
Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)] of IMC-11F8 at Study Day 1 of Cycle 1		Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose
Half-Life (t1/2) of IMC-11F8 at Study Day 1 of Cycle 1	The t1/2 is the time measured for the plasma concentration of the drug to decrease by one half.	Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose
Clearance (CL) of IMC-11F8 at Study Day 1 of Cycle 1	CL is the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time.	Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose
Volume of Distribution (Vss) of IMC-11F8 at Study Day 1 of Cycle 1	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.	Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose
Cmax at Study Day 1 of Cycles 2 Through 6		Day 1 Cycles 2 through 6 predose and 1 hour postdose
Area Under the Curve (AUC) at Study Day 1 of Cycles 2 Through 6		Day 1 Cycles 2 through 6 predose and 1 hour postdose
t1/2 at Study Day 1 of Cycles 2 Through 6		Day 1 Cycles 2 through 6 predose and 1 hour post dose
CL at Study Day 1 of Cycles 2 Through 6		Day 1 Cycles 2 through 6 predose and 1 hour postdose
Vss at Study Day 1 of Cycles 2 Through 6		Day 1 Cycles 2 through 6 predose and 1 hour postdose
Change From Baseline in Tumor Size		Baseline, 29 Months
Kirsten Rat Sarcoma (KRAS) Mutation Status	Tumor tissues collected prior to study drug administration were evaluated for the presence or absence of KRAS mutations by a retrospective analysis.	Baseline

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (ACTUAL): January 1, 2010
• Study Completion (ACTUAL): October 1, 2010

Study Registration Dates

• First Submitted: February 2, 2009
• First Submitted That Met QC Criteria: February 2, 2009
• First Posted (ESTIMATE): February 3, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): January 29, 2016
• Last Update Submitted That Met QC Criteria: December 21, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Antibodies, Monoclonal; Colorectal Neoplasms
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Hematinics; Oxaliplatin; Leucovorin; Levoleucovorin; Antibodies, Monoclonal; Folic Acid; Necitumumab
• Other Study ID Numbers: 13926; 2006-003147-23 (EUDRACT_NUMBER); CP11-0602 (OTHER: ImClone Systems); I4X-IE-JFCD (OTHER: Eli Lilly and Company)