E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Previously Untreated Metastatic Colorectal Cancer |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess whether panitumumab in combination with infusional 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy improves progression-free survival (PFS) compared to FOLFOX alone as first-line therapy for metastatic colorectal cancer (mCRC). |
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E.2.2 | Secondary objectives of the trial |
To evaluate overall survival (OS), objective response rate (ORR), duration of response (DOR), time to progression (TTP), and safety and tolerability |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Subjects with evidence of disease progression will be discontinued from treatment dosing and will be followed for safety (4 weeks after the last study drug administration) and survival (every 3 months until 30 months after the last subject is randomized). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 44 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 44 |