E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
previously untreated, wild-type RAS, potentially resectable colorectal cancer liver metastases |
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E.1.1.1 | Medical condition in easily understood language |
metastatic colorectal cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
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 |
Evaluation of efficacy and safety of perioperative treatment including panitumumab and FOLFIRI as first line therapy for mCRC in subjects with potentially resectable liver metastases expressing wild-type RAS |
|
E.2.2 | Secondary objectives of the trial |
- evaluation of proportion of patients who respond after 4 cycles of therapy without liver tissue damage - liver resection rate - evaluation of perioperative morbidity and mortality - evaluation of pathological response acc. to tumor regression rate - progression-free survival time (PFS) - overall survival (OS) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- histologically confirmed metastatic colorectal cancer with potentially resectable liver metastases - primary tumor in-situ or resected (in case of resected primary tumor, neoadjuvant short-time radiotherapy is allowed if terminated > 14 days prior to registration) - subjects with wild-type RAS tumor status confirmed by assessment of paraffin embedded tumor tissue from the primary tumor or metastases - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - at least one measurable metastatic lesion in the liver as per RECIST 1.1 guidelines using multislice 3 phase CT - man or woman > 18 years - hematologic function, as follows (< 28 days of registration): absolute neutrophil count (ANC) > 1.5 x 109/L; leucocyte count > 3.0 x 109g/L; platelet count > 100 x 109/L; hemoglobin > 9 x g/dL - renal function, as follows (< 28 days of registration): creatinin < 1.5 x upper limit of normal (ULN) - hepatic function, as follows (< 28 days of registration): aspartate aminotransferase (AST) < 5 x ULN in presence of liver metastases; alanine aminotransferase (ALT) < 5 x ULN in presence of liver metastases; total bilirubin < 1.5 x ULN - women of childbearing potential must have a negative pregnancy test done within 1 week before registration - 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 |
- prior chemotherapy for the treatment of current metastatic cancer (including biologics) - current extrahepatic metastatic disease - prior chemotherapy and/or resection of any metastases from mCRC <5 years - prior adjuvant or neoadjuvant (chemo-) therapy for the treatment of colorectal cancer ≤ 26 weeks prior to registration - radiotherapy ≤ 14 days prior to registration (patients must have recovered from all radiotherapy-related toxicities) - previous malignancy other than CRC in the last 5 years except basal cell carcinoma of the skin and/or in situ carcinoma of the cervix - active infection requiring systemic treatment or any uncontrolled infections < 14 days prior to registration - any investigational agent or therapy < 28 days before registration - clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) < 1 year before registration - known allergy or hypersensitivity to irinotecan, 5-FU, leucovorin or panitumumab - history of severe adverse events to iodinated contrast agents - history of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan - 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 - 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 anaesthesia) < 28 days - patients must have recovered from surgery-related toxicities - subject who is pregnant or breast feeding or planning to become pregnant within 6 months after the end of treatment - woman or man of childbearing potential not consenting to use adequate contraceptive precautions (double barrier contraceptive methods e.g. diaphragm plus condom), or abstinence during the course of the study and 6 months after the last study drug administration - subject unwilling or unable to comply with study requirements |
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E.5 End points |
E.5.1 | Primary end point(s) |
objective response rate (ORR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after neoadjuvant therapy (4 cycles) |
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E.5.2 | Secondary end point(s) |
- evaluation of ORR without liver tissue damage - resection rate - evaluation of perioperative morbidity and mortality - proportion of subjects with a complete pathological response - progression-free survival time (PFS) - overall survival (OS) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- ORR: after 4 cycles of therapy - Resection rate: after neoadjuvant chemotherapy - PFS: time from registration date to the date of first observed progression disease (PD) or death (whichever comes first) - OS: time from registration date to the date of death. |
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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 | No |
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 | No |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
E.8.7 | Trial has a data monitoring committee | No |
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
|
follow up period of 2 years after the end of adjuvant chemotherapy (routine 3 monthly follow up) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 14 |