E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic (liver metastases) colorectal cancer, with no prior chemotherapy.
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024700 |
E.1.2 | Term | Liver metastases |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
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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 |
Assessment of the efficacy of the combination of Bevacizumab with irinotecan- based chemotherapy (FOLFIRI) or oral capecitabine (XELIRI) in terms of resectability of the primary non-resectable liver metastases from metastatic colorectal cancer. |
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E.2.2 | Secondary objectives of the trial |
Assessment of disease free and overall survival of the patients who have undergone surgery for the metastases; Assessment of the overall and hepatic toxicity of the treatment; Peri- and postoperative complications and the quality of life of the patients; Assessment of the serum and tumor levels of the fibroblastic and hepatocyte growth factors, response and resectability of the liver metastases and survival.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent form prior to beginning specific protocol procedures showing the patients’ willingness and awareness to participate in the trial and comply with procedures
2. Age > 18 years
3. Patients with hystologically confirmed adenocarcinoma of the colon or the rectum.
4. Patients with colorectal cancer with nonresectable liver metastasis with resected or non resected primary tumor and lack of intestinal obstructions. Nonresectability is defined as: a. Engagement of the hepatic parenchyma more than 6 segments. b. Location of the lesions - near to large intrahepatic vessels – the two hepatic veins, vena cava,, lymphatic structures of the hepato-duodenal ligament and engagement of lymph nodes of truncus celiacus.
5. Six months progression free interval for patients who have been treated in adjuvant setting.
6. Patients with at least one target lesion, measured with CT scan < 4 weeks before the entrance in the study.
7. Patients with nonresectable extrahepatic disease.
8. ECOG ≤ 2
9. Patients with no prior chemotherapy of the advanced disease.
10. End of radiotherapy 2 weeks prior to entry into the study
11. Adequate bone – marrow function – (leucocytes > 3 x 10 9/L, thrombocytes > 100 x 10 9/L, Hg >10g/dl and normal hemostasis).
12. Adequate hepatic (bilirubine <1.5 UNL, ALAT and ASAT < 5 UNL) renal (serum creatinine < 1.5 UNL and creatinine clearance >60/min Cockroft Goult) function.
13. Negative pregnancy test for the women with childbearing potential.
14. Life expectancy more than 3 months. |
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E.4 | Principal exclusion criteria |
1. Patients with widespread metastatic disease as peritoneal metastases, multiple lung, bone or CNS metastases.
2. Patients with primary resectable liver metastases
3. Patients with hepatic insufficiency or severe hepatic disease (Child B and C) and clinically significant renal disease.
4. Patients with clinically significant heart disease (unstable angina pectoris, myocardial infarction, medicinally uncontrolled arterial hypertension, heart failure grade II or higher classified by NYHA, arrhythmia that needs medicinal treatment.
5. Patients with systemic anticoagulant therapy. Prophylactic anticoagulation for venous access devices is allowed provided the activity of the agent does not change INR or PTT measurements.
6. Use of aspirin on a regular basis at dose higher than 325 mg/day within 10 days prior to entry into the study
7. Serious, non-healing wound, ulcer, or bone fracture
8. Patients with serious infections – uncontrolled or that will need treatment.
9. Patients with severe CNS disorders – recent cerebro-vasular incident, epilepsy and psychiatric disorders.
10. Patient with uncontrolled diabetes.
11. Patient with another malignant disease in the last 5 years, excluding basocellular carcinoma of the skin or carcinoma in situ of the cervix.
12. Participation in another clinical study.
13. Men or women with childbearing potential who refuse to use effective contraception |
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of effect of neoadjuvant combination of FOLFIRI or XELIRI chemotherapy regimen and bevacizumab on the resectability of liver metastases initially assessed as unresectable. |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |