A Randomized, Multicenter Phase 3 Study to Compare the Efficacy of Panitumumab in Combination with Chemotherapy to the Efficacy of Chemotherapy Alone in Patients with Previously Treated Metastatic Colorectal Cancer

• Conditions: Patients with Previously Treated Metastatic Colorectal Cancer

• Registration Number: EUCTR2005-004676-20-FI
• Lead Sponsor: Amgen Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-05-02
• Last Update Posted: 3 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1100

Inclusion Criteria

• Histologically or cytologically-confirmed adenocarcinoma of the colon or rectum in patients who are presenting with metastatic disease
• One and only one prior chemotherapy regimen for mCRC consisting of first-line fluoropyrimidine-based chemotherapy. (Prior adjuvant fluoropyrimidine-based
chemotherapy is allowed)
• Radiographically documented disease progression per modified RECIST criteria either while receiving or = 6 months after the last dose of prior first-line fluoropyrimidine-based chemotherapy for mCRC
• At least 1 uni-dimensionally measurable lesion of at least 20 mm per modified RECIST criteria. (All sites of disease must be evaluated = 28 days prior to enrollment)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Paraffin-embedded tumor tissue from the primary tumor or metastasis available for central analyses of EGFr and biomarker testing
• Man or woman = 18 years of age
• Hematologic function, as follows (= 7 days of randomization):
o Absolute neutrophil count (ANC) = 1.5 x
109/L
o Platelet count = 100 x 109/L
o Hemoglobin = 9 g/dL
• Renal function, as follows (= 7 days of randomization):
o Creatinine = 1.5 x upper limit of normal
(ULN)
• Hepatic function, as follows (= 7 days of randomization):
o Aspartate aminotransferase (AST) = 3 x ULN (if liver metastases = 5 x ULN)
o Alanine aminotransferase (ALT) = 3 x ULN(if liver metastases = 5 x ULN)
o Total bilirubin = 1.5 x ULN
• Metabolic function, as follows (= 7 days of randomization):
o Magnesium = lower limit of normal
• Negative pregnancy test = 72 hours of randomization (females of childbearing
potential only)
• Competent to comprehend, sign, and date an IEC/IRB-approved informed consent form
• Life expectancy = 3 months
Are the trial subjects under 18?
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• History or known presence of central nervous system (CNS) metastases
• History of another primary cancer, except:
o Curatively treated in situ cervical cancer, or
o Curatively resected non-melanoma skin cancer, or
o Other primary solid tumor curatively treated with no known active disease present and no treatment administered for = 5 years prior to randomization
• Prior irinotecan therapy
• Prior anti-EGFr antibody therapy (eg, cetuximab) or treatment with small molecule EGFr inhibitors (eg, erlotinib)
• Systemic chemotherapy, hormonal therapy, immunotherapy or experimental or approved proteins/antibodies (eg, bevacizumab) = 30 days before randomization
• Unresolved toxicities from prior systemic therapy that, in the opinion of the investigator, does not qualify the patient for randomization
• Radiotherapy = 14 days prior to randomization. Patients must have recovered from all radiotherapy-related toxicities
• Active infection requiring systemic treatment or any uncontrolled infection = 14 days prior to randomization
• CYP3A4 enzyme inducing anti-convulsant medication (eg phenytoin, phenobarbital or carbamazepine), rifampin and rifabutin, and St. John’s Wort = 14 days before randomization
• Ketoconazole = 7 days before randomization (Itraconazole should be used with caution)
• Any investigational agent or therapy = 30 days before randomization
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) = 1 year before randomization
• Known allergy or hypersensitivity to irinotecan, 5-FU or leucovorin
• History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan
• Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as > CTC grade 2 [CTCAE version 3.0])
• Known positive test(s) for human immunodeficiency virus (HIV) infection, hepatitis C
virus, acute or chronic active hepatitis B infection
• Any co-morbid disease or condition that could increase the risk of toxicity (eg dihydropyrimidine deficiency, significant ascites or pleural effusion)
• Any uncontrolled concurrent illness or history of any medical condition that may interfere with the interpretation of the study results
• Major surgical procedure (requiring general anesthesia) = 28 days or minor surgical procedure (excluding central venous catheter placement) = 14 days before randomization. Patients must have recovered from surgery related toxicities
• Subject who is pregnant or breast feeding
• Woman or man of childbearing potential not consenting to use adequate contraceptive precautions ie. double barrier contraceptive methods (eg diaphragm plus condom), or abstinence during the course of the study and for 6 months after the last study drug administration for women, and 1 month for men
• Subject unwilling or unable to comply with study requirements
• Previously randomized into this study protocol

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the treatment effect of panitumumab plus FOLFIRI on overall survival(OS) and progression-free survival (PFS) compared to FOLFIRI alone as second line therapy for metastatic colorectal cancer.;Secondary Objective: To evaluate objective response rate (ORR), time to progression (TTP), duration of<br>response (DOR), and safety (incidence of AEs and significant laboratory changes).;Primary end point(s): Efficacy: Overall survival (OS) and progression free survival (PFS)