Clinical trial NCT00835185: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Antibodies, Monoclonal
Colorectal Neoplasms
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-02-03
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response )
timeFrame: Up to 30 Months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: First dose to date of death from any cause up to 30 months
measure: Progression-Free Survival (PFS)
timeFrame: First dose to measured PD or death up to 30 months
measure: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs) or Death
timeFrame: First dose to end of treatment and 30-day post treatment follow-up up to 31 months
measure: Duration of Response
timeFrame: Time of response to time of measured PD or death up to 30 months
measure: Serum Anti-IMC-11F8 Antibody Assessment (Immunogenicity)
timeFrame: Baseline up to last day of treatment plus 45 days after last treatment (127 weeks)
measure: Maximum Concentration (Cmax) of IMC-11F8 at Study Day 1 of Cycle 1
timeFrame: Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose
measure: Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)] of IMC-11F8 at Study Day 1 of Cycle 1
timeFrame: Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose
measure: Half-Life (t1/2) of IMC-11F8 at Study Day 1 of Cycle 1
timeFrame: Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose
measure: Clearance (CL) of IMC-11F8 at Study Day 1 of Cycle 1
timeFrame: Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose
measure: Volume of Distribution (Vss) of IMC-11F8 at Study Day 1 of Cycle 1
timeFrame: Cycle 1 Day 1 predose, immediately after infusion, and 1, 2, 4, 24, 72, 96, 144, 168 and 236 hours postdose
measure: Cmax at Study Day 1 of Cycles 2 Through 6
timeFrame: Day 1 Cycles 2 through 6 predose and 1 hour postdose
measure: Area Under the Curve (AUC) at Study Day 1 of Cycles 2 Through 6
timeFrame: Day 1 Cycles 2 through 6 predose and 1 hour postdose
measure: t1/2 at Study Day 1 of Cycles 2 Through 6
timeFrame: Day 1 Cycles 2 through 6 predose and 1 hour post dose
measure: CL at Study Day 1 of Cycles 2 Through 6
timeFrame: Day 1 Cycles 2 through 6 predose and 1 hour postdose
measure: Vss at Study Day 1 of Cycles 2 Through 6
timeFrame: Day 1 Cycles 2 through 6 predose and 1 hour postdose
measure: Change From Baseline in Tumor Size
timeFrame: Baseline, 29 Months
measure: Kirsten Rat Sarcoma (KRAS) Mutation Status
timeFrame: Baseline
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: ImClone Investigational Site
city: Haine Saint-Paul
country: Belgium
facility: ImClone Investigational Site
city: Barcelona
country: Spain
facility: ImClone Investigational Site
city: Madrid
country: Spain
facility: ImClone Investigational Site
city: Valencia
country: Spain
facility: ImClone Investigational Site
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: