previously untreated metastatic colorectal carcinoma MedDRA version: 16.1 Level: LLT Classification code 10010036 Term: Colorectal carcinoma System Organ Class: 100000004864
Conditions
Sponsors
Roche Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Age >= 18 years and = 2 cm (conventional technique) and >=1 cm (spiral CT), respectively (according to RECIST criteria), which is primarily not resectable. 3.Laboratory parameters: Hematology: –Neutrophils > 1,500/µl –Platelets > 100,000/µl –Hemoglobin >= 9 g/dl or 5.59 mmol/l –INR >=1.5 x ULN and aPTT ? 1.5 x ULN within 7 days prior to treatment start Blood chemistry: –Creatinine clearance > 30 ml/min, serum creatinine =2+ proteinuria on dipstick urinalysis, who demonstrate 3 months. 6.Willingness to give written informed consent, writ¬ten consent for data protection (legal requirement in Germany: Datenschutzrechtliche Einwilligung) and willingness to participate and to comply with the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: 1.Prior chemotherapy for metastatic CRC 2.Adjuvant / neoadjuvant chemotherapy or radio-chemotherapy of a non-metastatic malignancy completed = II. 6.Current or recent serious polyneuropathy (grade >= 1 according to NCI CTCAE v3.0 classification; exception: absence of tendon reflexes). 7.Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study. 8.Serious non-healing wound, ulcer or bone fracture. 9.Evidence of bleeding diathesis or coagulopathy. 10.Hemapoetic diseases. 11.Known intra-abdominal inflammatory process or serious gastrointestinal ulceration. 12.History of chronic intestinal diseases associated with severe diarrhea. 13.Known dihydropyrimidine dehydrogenase (DPD) deficien¬cy. 14.Thromboembolic events or severe hemorrhage (>= 6 months before treatment start). 15.Known hypersensitivity to the test drug bevacizumab or a compound of the background medication [5- fluorouracil (5-FU), folinic acid (FA; leukovorin), or oxaliplatin, irinotecan]. 16.Allogen transplants requiring immunosuppressive therapy. 17.Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications. 18.As the following medication(s) can have interactive effects and may interfere with the patient's ability to meet the study requirements, they cannot be administered during the clinical study: –Sorivudin or analog compounds. –Current or recent (within 10 days of first dose of study treatment) treatment with full-dose oral or parenteral anticoagulants or thrombolytic agents (e.g., marcumar therapy) for therapeutic purposes. –Current or recent (within 10 days of first dose of study treatment) chronic use of aspirin (> 325 mg/day) or clopidogrel (> 75 mg/day). 19.Patients who participate currently in another clinical trial or patients who participated in another clinical trial during the last 30 days prior to enrolment. 20.Patients who have participated in this study before. 21.Women, lactating, pregnant or of childbearing potential and fertile men not using a highly effective contraceptive method . [Women of childbearing potential must have a negative pregnancy test (serum beta-HCG) within 7 days before the first dose of study drug]. 22.Patients who are committed to an institution by virtue of an order issued either by the judicial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluation of progression-free survival (PFS) under a therapy with bevacizumab based on a FOLFOXIRI regimen in patients with previously untreated metastatic colorectal carcinoma. ;Secondary Objective: -Further evaluation of the efficacy of a therapy with bevacizumab based on a FOLFOXIRI regimen. -Determination of the feasibility and safety of a therapy with bevacizumab based on a FOLFOXIRI regimen.;Primary end point(s): Progression free survival (PFS);Timepoint(s) of evaluation of this end point: An interim analysis of the study is scheduled 18 month after inclusion of first patient. Final analysis at end of study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary variables for efficacy are: • Overall survival • Proportion of patients who achieve R0 resectability • Objective response rate (complete response [CR] and partial response [PR] ) The secondary variable for feasibility is: • Proportion of patients completing 12 cycles of chemotherapy [or up to PD; whichever comes first]. Patients who did achieve resectability until the 12th cycle will be analyzed separately. The secondary parameters for safety are: • All adverse events. • Adverse events with NCI CTCAE v3.0 Grade 3, 4, or 5. • Adverse events of special interest (diarrhea of grade 2 according to NCI CTCAE v3.0 as well as any grade of gastrointestinal perforation, gastrointestinal fistulas or other internal fistulas, wound-healing distur¬bances, hemorrhagic events and arterial thrombo¬embolic events). • Changes in laboratory values and vital signs. • Changes in ECOG performance status ;Timepoint(s) of evaluation of this end point: An interim analysis of the study is scheduled 18 month after inclusion of first patient. Final analysis at end of study. | — |
Countries
Germany
Outcome results
None listed