OPA

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

1.Age >= 18 years and <= 70 years
2.Indication:
–Histologically confirmed diagnosis of metastatic CRC scheduled to start 1st line chemotherapeutic treat¬ment.
–At least 1 measurable lesion of >= 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 < 1.5 x ULN
–Serum bilirubin < 1.5 x ULN
–Alkaline phosphatase and transaminases < 2.5 x ULN (in case of liver metastases < 5 x ULN)
Proteinuria:
–Patients with < 2+ proteinuria on dipstick urinalysis.
–Patients with >=2+ proteinuria on dipstick urinalysis, who demonstrate < 1.0 g of protein/24 h on 24-h urine
collection.
4.ECOG performance score 0 – 1.
5.Life expectancy > 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

1.Prior chemotherapy for metastatic CRC
2.Adjuvant / neoadjuvant chemotherapy or radio-chemotherapy of a non-metastatic malignancy completed < 6
months prior to treatment start.
3.Concomitant malignancies other than CRC (Patients with curatively treated basal and squamous cell carcinoma
of the skin and / or in-situ carcinoma of the cervix are eligible).
4.Evidence of current central nervous system (CNS) metastases or spinal cord compression. If clinically
indicated, patient must undergo a MRI or CT scan of the brain (with contrast, if possible) within 28 days prior to
inclusion.
5.Clinically significant cardiovascular diseases, e.g., uncontrolled hypertension, arrhythmia requiring medication,
hemoptoe, cardiovascular accident within the last 6 months before treatment start, unstable angina, congestive
heart failure (CHF) NYHA grade III/IV, symptomatic coronary heart disease, myocardial infarction within the
last year before treatment start, peripheral arterial disease stage >= 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluation of progression-free survival (PFS) under a therapy with bevacizumab based on a FOLFOXIRI<br>regimen in patients with previously untreated metastatic colorectal carcinoma.<br>;Secondary Objective: -Further evaluation of the efficacy of a therapy with bevacizumab based on a FOLFOXIRI regimen.<br>-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 Outcome Measures