E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Previously Treated 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 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. |
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E.2.2 | Secondary objectives of the trial |
To evaluate objective response rate (ORR), time to progression (TTP), duration of response (DOR), and safety (incidence of AEs and significant laboratory changes). |
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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 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 |
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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 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: Overall survival (OS) and 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 | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 (30 ± 3 days after the last study drug administration) and survival (every 3 months ± 28 days until up to 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 | 50 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 50 |