Patients with Previously Untreated Metastatic Colorectal Cancer
Conditions
Interventions
Product Name: Panitumumab
Product Code: AMG 954
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Panitumumab
Current Sponsor code: AMG 954
Concentration unit: mg/ml milligram(s)/millili
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically or cytologically-confirmed adenocarcinoma of the colon or rectum in subjects who are presenting with metastatic disease • At least 1 uni-dimensionally measurable lesion of at least 20mm per modified RECIST guidelines (all sites of disease must be evaluated = 28 days prior to randomization) • 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 prior to 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 prior to randomization): o Estimated creatinine clearance > 50 ml/min • Hepatic function, as follows (=7 days prior to 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 prior to randomization): o Magnesium = lower limit of normal • Negative pregnancy test = 72 hours prior to 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? no 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
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 before randomization • Prior chemotherapy or systemic therapy for the treatment of metastatic colorectal carcinoma with the following exceptions: o Subject may have received adjuvant fluoropyrimidine-based chemotherapy if disease progression is documented at least 6 months after completion of chemotherapy o Subjects may have received prior fluoropyrimidine therapy if administered solely for the purpose of radiosensitization • Prior oxaliplatin therapy • Prior anti-EGFr antibody therapy (eg, cetuximab) or treatment with small molecule EGFr inhibitors (eg, erlotinib) • Any investigational agent or therapy = 30 days prior to randomization • Radiotherapy = 14 days prior to randomization. Subjects must have recovered from all radiotherapy related toxicities • Known allergy or hypersensitivity to platinum-containing medications, 5-FU or leucovorin • Active infection requiring systemic treatment or any uncontrolled infection = 14 days prior to randomization • Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) = 1 year prior to randomization • 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 tests 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 • Peripheral sensory neuropathy with functional impairment (> CTC grade 3 [CTCAE version 3.0] neuropathy, regardless of causality) • 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 prior to randomization. Subjects must have recovered from surgery related toxicities. • Subject who is pregnant or breast feeding • Woman or man of child-bearing 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether panitumumab in combination with infusional 5- fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy improves progressionfree survival (PFS) compared to FOLFOX alone as first-line therapy for metastatic colorectal cancer (mCRC) among subjects with wild-type KRAS tumors (subjects whose tumors contain non-mutated KRAS) and subjects with mutant KRAS tumors.;Secondary Objective: To evaluate overall survival (OS), objective response rate (ORR), duration of response (DOR), time to progression (TTP), and safety and tolerability among subjects with wild-type KRAS tumors and subjects with mutant KRAS tumors.;Primary end point(s): Progression-free survival (PFS) | — |
Countries
Belgium, Czech Republic, Estonia, Hungary, Italy, Latvia, Spain, United Kingdom
Outcome results
None listed