Clinical trial NCT00862784: A Study of IMC-1121B (Ramucirumab) in Colorectal Cancer
Official title: An Open Label, Multicenter, Phase 2 Study Evaluating the Safety and Efficacy of IMC-1121B in Combination With 5-FU/FA and Oxaliplatin (Modified FOLFOX-6) as First-line Therapy in Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Carcinoma
Keywords: Colorectal carcinoma
CRC
Colon Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-03-17
Enrollment: 48
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 test how long participants with colorectal cancer live without progressive disease when being treated with IMC-1121B (ramucirumab) and the modified FOLFOX-6 chemotherapy.

Detailed description: The purpose of this study is to evaluate the progression-free survival (PFS) in participants with metastatic colorectal cancer when treated with the monoclonal antibody IMC-1121B (ramucirumab) in combination with the modified FOLFOX-6 \[folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6\] chemotherapy regimen as first-line therapy.

Eligibility criteria: Inclusion Criteria:

* The participant must have histologically confirmed adenocarcinoma of the colon or rectum that is locally-advanced or metastatic and unresectable
* The participant has at least one unidimensionally-measurable target lesion \[≥ 2 centimeters (cm) with conventional techniques or ≥ 1 cm with spiral computed tomography (CT) scan or magnetic resonance imaging (MRI), as defined by Response Evaluation Criteria in Solid Tumors (RECIST)\]; target lesion(s) must not lie within an irradiated area. Participants with locally advanced rectal carcinoma who have undergone previous radiation must have documented evidence of disease progression in the pelvis in order to participate
* The participant is age ≥ 18 years
* The participant has a life expectancy of ≥ 6 months
* The participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 at study entry
* The participant has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥ 1500/microliter (μL), hemoglobin ≥ 10 grams/deciliter (g/dL), and platelets ≥ 100,000/μL
* The participant has adequate hepatic function as defined by: total bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN (or 5.0 x ULN in the case of liver metastases), and serum albumin ≥ lower limit of normal (LLN) institutional range or (if \< LLN) within 10% of the LLN
* The participant has adequate renal function as defined by a serum creatinine ≤ 1.5 x ULN, or creatinine clearance (measured via 24-hour urine collection) ≥ 60 milliliters/minute (mL/min)
* The participant's urinary protein ≤ 1+ on dipstick or routine urinalysis \[(UA); if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine for protein must demonstrate \< 1000 milligrams (mg) of protein in 24 hours to allow participation in the study\]
* The participant must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight (LMW) heparin and if on warfarin, must have an INR between 2 and 3 and no active bleeding or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices)
* The participant has resolution to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3 (NCI-CTCAE v 3.0) of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of peripheral neuropathy which must have resolved to Grade 0
* The participant agrees to use adequate contraception during the study period and for 8 weeks after the last dose of study treatment
* The participant has provided signed informed consent

Exclusion Criteria:

* The participant has received prior systemic chemotherapy for locally-advanced unresectable or metastatic colorectal cancer (CRC). Prior adjuvant chemotherapy is allowed if disease progression has been documented \> 6 months after the end of the last cycle of adjuvant chemotherapy or \> 12 months after the end of the last cycle of adjuvant oxaliplatin-containing regimens
* The participant has documented and/or symptomatic brain or leptomeningeal metastases
* The participant has participated in clinical studies of non-approved experimental agents or procedures within 12 weeks of study entry
* The participant has received previous therapy with monoclonal antibodies
* The participant has received previous therapy with any agent that targets vascular endothelial growth factor (VEGF) or VEGF receptor-2 (VEGFR-2) (including multi-targeted tyrosine kinase inhibitors)
* The participant has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator
* The participant is on chronic non-topical corticosteroid treatment for \> 6 months at doses \> 10 mg/day of prednisolone or equivalent before study entry, which in the opinion of the investigator could compromise the participant or the study
* The participant has a known dihydropyrimidine dehydrogenase (DPD) deficiency
* The participant has a known allergy to any of the treatment components
* The participant has an acute or subacute intestinal obstruction
* The participant has uncontrolled or poorly controlled hypertension on a standard regimen of anti-hypertensive therapy
* The participant has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that he/she has been disease free for \> 3 years
* The participant, if female, is pregnant
* Has had prior autologous or allogeneic organ or tissue transplantation
* Has interstitial pneumonia or interstitial fibrosis of the lung, which in the opinion of the investigator could compromise the participant or the study
* Has pleural effusion or ascites that causes \> Grade 1 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
* Has undergone major surgery within 28 days prior to the first dose of study medication, or subcutaneous venous access device placement within 7 days prior to the first dose of study medication

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: First dose to measured progressive disease or death due to any cause up to 28.1 months
Secondary outcomes:
measure: Percentage of Participants With Complete Response or Partial Response [Objective Response Rate (ORR)]
timeFrame: First dose to date of objective progressive disease up to 23.8 months
measure: Overall Survival (OS)
timeFrame: First dose to death due to any cause up to 28.1 months
measure: Duration of Response
timeFrame: Time of response to time of measured progressive disease up to 22.2 months
measure: Number of Participants With IMC-1121B (Ramucirumab)-Related Adverse Events (AEs)
timeFrame: First dose to 25.2 months
measure: Number of Participants With IMC-1121B (Ramucirumab)-Related Severe Adverse Events (SAEs)
timeFrame: First dose to 25.2 months
measure: Maximum Concentration (Cmax) at Day 1 of Cycle 1
timeFrame: Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1)
measure: Area Under the Concentration (AUC) at Day 1 of Cycle 1
timeFrame: Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1)
measure: Half-Life (t1/2) at Day 1 of Cycle 1
timeFrame: Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1)
measure: Clearance (CL) at Day 1 of Cycle 1
timeFrame: Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1)
measure: Steady State Volume of Distribution (Vss) at Day 1 of Cycle 1
timeFrame: Baseline, 1, 168, and 336 hours post infusion Day 1 (Cycle 1)
measure: Maximum Concentration (Cmax) at Day 1 of Cycles 5, 9, 13, 17, and 21
timeFrame: Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)
measure: Area Under the Concentration (AUC) at Day 1 of Cycles 5, 9, 13, 17, and 21
timeFrame: Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)
measure: Half-Life (t1/2) at Day 1 of Cycles 5, 9, 13, 17, and 21
timeFrame: Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)
measure: Clearance (CL) at Day 1 of Cycles 5, 9, 13, 17, and 21
timeFrame: Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)
measure: Steady State Volume of Distribution (Vss) at Day 1 of Cycles 5, 9, 13, 17, and 21
timeFrame: Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)
measure: Serum Anti-IMC-1121B (Immunogenicity) at Day 1
timeFrame: Day 1 (Cycles 1, 5, 9, and 30-day follow-up)
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: ImClone Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: ImClone Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: ImClone Investigational Site
state: Quebec
city: Barcelona
country: Spain
facility: ImClone Investigational Site
city: Santander
country: Spain
facility: ImClone Investigational Site
city: Seville
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: