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Study of IMC-11F8 in Participants With Colorectal Cancer

Primary Purpose

Metastatic Colorectal Cancer

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

IMC-11F8 (necitumumab)

Oxaliplatin

Folinic acid (FA)

5-FU

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Antibodies, Monoclonal, Colorectal Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

ImClone Investigational Site
ImClone Investigational Site
ImClone Investigational Site
ImClone Investigational Site
ImClone Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IMC-11F8 (necitumumab) /mFOLFOX-6 regimen

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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

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

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.

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.

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.

Cmax at Study Day 1 of Cycles 2 Through 6

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

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

CL at Study Day 1 of Cycles 2 Through 6

Vss at Study Day 1 of Cycles 2 Through 6

Change From Baseline in Tumor Size

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.

Full Information

NCT ID

NCT00835185

First Posted

February 2, 2009

Last Updated

December 21, 2015

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00835185

Brief Title

Study of IMC-11F8 in Participants With Colorectal Cancer

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Completed

Study Start Date

August 2007 (undefined)

Primary Completion Date

January 2010 (Actual)

Study Completion Date

October 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Colorectal Cancer

Keywords

Antibodies, Monoclonal, Colorectal Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

IMC-11F8 (necitumumab) /mFOLFOX-6 regimen

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

IMC-11F8 (necitumumab)

Other Intervention Name(s)

Necitumumab, IMC-11F8, LY3012211, Portrazza®

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Folinic acid (FA)

Intervention Description

FA 400 mg/m² IV infusion bolus injection

Intervention Type

Drug

Intervention Name(s)

5-FU

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Up to 30 Months

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Description

Time Frame

First dose to date of death from any cause up to 30 months

Title

Progression-Free Survival (PFS)

Description

Time Frame

First dose to measured PD or death up to 30 months

Title

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

Description

Time Frame

First dose to end of treatment and 30-day post treatment follow-up up to 31 months

Title

Duration of Response

Description

Time Frame

Time of response to time of measured PD or death up to 30 months

Title

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

Description

Time Frame

Baseline up to last day of treatment plus 45 days after last treatment (127 weeks)

Title

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

Time Frame