E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic colorectal cancer |
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E.1.1.1 | Medical condition in easily understood language |
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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 |
To evaluate the objective response rates (CR and PR) of FOLFIRI plus aflibercept as 1st line treatment in patients with mCRC. |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the progression-free survival (PFS) in patients with mCRC who achieved complete or partial response or stable disease after 1st-line treatment with FOLFIRI plus aflibercept. •To assess the median overall survival in the study population •To evaluate the safety of FOLFIRI plus aflibercept in patients with mCRC.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with histologically documented adenocarcinomas of colon or rectum with unresectable metastatic disease. • No prior treatment for metastatic disease • Metastatic liver disease assessable with diffusion-weighted MR Imaging. • No previous treatment with bevacizumab or Cetuximab or Panitumumab. • Patients may have receive fluoropyrimidines with or without oxaliplatin as adjuvant treatment, if they have progressed > 12 months after the end of the last cycle of the adjuvant treatment • Performance Status (ECOG) 0-2 • Life expectancy ≥ 3 months. • Effective contraception for both male and female subjects if the risk of conception exists. • Adequate laboratory parameters: Absolute neutrophils count ≥ 1.5 x 109 /L, Platelets ≥ 100 x 109 /L, Leucocytes > 3,000/mm; Hemoglobin> 10.5g/dl, creatinine clearance ≥ 60 ml/min, Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour, Magnesium ≥ lower limit of normal, Calcium ≥ lower limit of normal, total Bilirubin ≤ 1.5 times the upper limit of normal; aspartate and alanine aminotransferase ≤ 3 times of the upper normal limit in absence of liver metastases, or ≤5xUNL in presence of liver metastases, alkaline phosphatases < 5xULN • All patients will have to sign written informed consent in order to participate in the study. • Female patients must commit to using reliable and appropriate methods of contraception until at least three months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial |
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E.4 | Principal exclusion criteria |
• Known hypersensitivity reaction to the component of the treatment. • Inability to underwent a diffusion-weighted MR Imaging at baseline and in predefined time points • Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment. • History or evidence upon physical examination of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy), • Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy), • Treatment with any other investigational medicinal product within 28 days prior to study entry. • Other serious and uncontrolled non-malignant disease • Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy. • Gilbert's syndrome • Intolerance to atropine sulfate or loperamide • Known dihydropyrimidine dehydrogenase deficiency • Treatment with CYP3A4 inducers unless discontinued > 7 days prior to randomization • Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis • Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days • INR in absence of anticoagulation therapy > 1.25 or poorly controlled anti-coagulation therapy on coumadin or heparin compounds (INR >3.0) • History of myocardial infarction and/or stroke within 6 months prior to randomization, NYHA class III and IV congestive heart failure • History of life threatening (grade 4) venous thromboembolic events (including pulmonary embolism) within 6 months prior to registration, • Bowel obstruction • Legal incapacity or limited legal capacity. • Medical or psychological condition which in the opinion of the investigator would not permit the subject to complete the study or sign meaningful informed consent. • A second primary tumour other than non-melanoma skin cancer or in situ cervical cancer. • History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on chest CT scan. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the objective response rates (CR and PR) of FOLFIRI plus aflibercept as 1st line treatment in patients with mCRC. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
To be evaluated at the end of the study. It will also be an interim analysis of the first 30 evaluable patients will be included in the study. |
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E.5.2 | Secondary end point(s) |
•To evaluate the progression-free survival (PFS) in patients with mCRC who achieved complete or partial response or stable disease after 1st-line treatment with FOLFIRI plus aflibercept. •To assess the median overall survival in the study population •To evaluate the safety of FOLFIRI plus aflibercept in patients with mCRC. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
To be evaluated at the end of the study. It will also be an interim analysis of the first 30 evaluable patients will be included in the study. |
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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 | 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.8.3 |
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 | 9 |
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
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Patients in this study will be treated and followed up for a maximum 6 months (12 cycles). Patients start study treatment at Visit 1 and continue to be treated as per protocol for 6 months (alfibercept plus FOLFIRI) or until documented disease progression as per local radiology according to RECIST 1.1, until appearance of unacceptable toxicities or patient refusal to continue treatment. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |