Study of IMC-11F8 in Participants With Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00835185
First received: February 2, 2009
Last updated: December 21, 2015
Last verified: December 2015
  Purpose
The purpose of this study is to determine if IMC-11F8 in combination with chemotherapy is effective in treating colorectal cancer (CRC).

Condition Intervention Phase
Metastatic Colorectal Cancer
Biological: IMC-11F8 (necitumumab)
Drug: Oxaliplatin
Drug: Folinic acid (FA)
Drug: 5-FU
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response ) [ Time Frame: Up to 30 Months ] [ Designated as safety issue: No ]
    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) [ Time Frame: First dose to date of death from any cause up to 30 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: First dose to measured PD or death up to 30 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: First dose to end of treatment and 30-day post treatment follow-up up to 31 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Time of response to time of measured PD or death up to 30 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline up to last day of treatment plus 45 days after last treatment (127 weeks) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose ] [ Designated as safety issue: No ]
  • Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)] of IMC-11F8 at Study Day 1 of Cycle 1 [ Time Frame: Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose ] [ Designated as safety issue: No ]
  • Half-Life (t1/2) of IMC-11F8 at Study Day 1 of Cycle 1 [ Time Frame: Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 Cycles 2 through 6 predose and 1 hour postdose ] [ Designated as safety issue: No ]
  • Area Under the Curve (AUC) at Study Day 1 of Cycles 2 Through 6 [ Time Frame: Day 1 Cycles 2 through 6 predose and 1 hour postdose ] [ Designated as safety issue: No ]
  • t1/2 at Study Day 1 of Cycles 2 Through 6 [ Time Frame: Day 1 Cycles 2 through 6 predose and 1 hour post dose ] [ Designated as safety issue: No ]
  • CL at Study Day 1 of Cycles 2 Through 6 [ Time Frame: Day 1 Cycles 2 through 6 predose and 1 hour postdose ] [ Designated as safety issue: No ]
  • Vss at Study Day 1 of Cycles 2 Through 6 [ Time Frame: Day 1 Cycles 2 through 6 predose and 1 hour postdose ] [ Designated as safety issue: No ]
  • Change From Baseline in Tumor Size [ Time Frame: Baseline, 29 Months ] [ Designated as safety issue: No ]
  • Kirsten Rat Sarcoma (KRAS) Mutation Status [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Tumor tissues collected prior to study drug administration were evaluated for the presence or absence of KRAS mutations by a retrospective analysis.


Enrollment: 44
Study Start Date: August 2007
Study Completion Date: October 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Necitumumab
  • IMC-11F8
  • LY3012211
  • Portrazza®
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00835185

Locations
Belgium
ImClone Investigational Site
Brussels, Belgium, 1000
ImClone Investigational Site
Haine Saint-Paul, Belgium, 7100
Spain
ImClone Investigational Site
Barcelona, Spain, 08035
ImClone Investigational Site
Madrid, Spain, 28040
ImClone Investigational Site
Valencia, Spain, 46010
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00835185     History of Changes
Other Study ID Numbers: 13926  2006-003147-23  CP11-0602  I4X-IE-JFCD 
Study First Received: February 2, 2009
Results First Received: December 21, 2015
Last Updated: December 21, 2015
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Eli Lilly and Company:
Antibodies, Monoclonal
Colorectal Neoplasms

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Antibodies, Monoclonal
Oxaliplatin
Antineoplastic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on May 02, 2016