Phase II study on curative resectability of not optimally resectable liver and/or lung metastases from colorectal carcinoma (CRC) under intensified chemotherapy (FLOFOXIRI/Bevacizumab). - APRIORI

• Conditions: Advanced colorectal carcinoma of UICC stage IV, liver and/or lung metastases only, not optimally resectable; MedDRA version: 9.1Level: LLTClassification code 10010036Term: Colorectal carcinoma

• Registration Number: EUCTR2007-004535-33-DE
• Lead Sponsor: niversitätsklinikum Heidelberg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-03-09
• Last Update Posted: 4 February 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Age =18 years
2. Indication:
- Histologically confirmed advanced colorectal carcinoma of UICC Stages IV with liver and/or lung only metastases, which are not optimally resectable.
- Measurable disease according to RECIST criteria.
- In case of liver metastases: 70% liver replacement and/or > 6 segments tumor involved, and/or involvement of all three hepatic veins, and/or involvement of the right and left portal pedical, and/ or involvement of the vena cava.
- In case of lung metastases: No tumor with direct infiltration of myocardium, esophageous, spine or intrapericardial large vessels. Preoperative data indicate a significant loss of pulmonary function after pulmonary metastasectomy with severe impairment of quality of life.
3. ECOG performance status of < 2.
4. Life expectancy of > 3 months
5. Laboratory parameters:
Proteinuria at baseline:
- Patients with proteinuria <2+ on dip¬stick urinalysis.
- Patients with 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 h urine collection and must have proteinuria >= 1 g of protein/24 h.
The required laboratory values at baseline are as follows:
Hematology:
º Absolute neutrophil count (ANC) > 1.5 x 109/L
º Platelet count > 100 x 109/L
º Haemoglobin > 9 g/dL (may be transfused to maintain or exceed this level)
º International Normalized Ratio (INR) < 1.5; APTT <1.5 x ULN
Biochemistry:
º Total bilirubin < 1.5 x upper limit of normal (UNRL)
º AST, ALT < 2.5 x UNRL in patients without liver metastases; < 5 x UNRL in patients with liver metastases
º Serum creatinine <2.0 mg/dL or 177 1.µmol/L
6. Willingness to give written informed consent, written 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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Past or current history of malignancies other than colorectal carcinoma. Patients with curatively treated basal and squamous cell carcinoma of the skin and/or in-situ carcinoma of the cervix are eligible.
2. Previous chemotherapy.
3. Extrahepatic and/or extrapulmonary metastases except of the initially removed lymph node metastases.
4. History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke).
5.Major surgical procedures, open biopsy, or significant traumatic injury within 28 days prior to study treatment start (wound healing has to be completed), or anticipation of the need for major surgical procedure during the course of the study.
6. Evidence of bleeding diathesis or coagulopathy
7. Serious, non-healing wound, ulcer, or bone fracture
8. Treatment with investigational agents or participation in clinical trials within 30 days before study entry.
9. Clinically significant (i.e. active) cardiovascular disease, e.g., uncontrolled hypertension, cerebrovascular accidents (= 6 months prior to treatment start), myocardial infarction (= 6 months prior to treatment start), unstable angina, New York Heart Association (NYHA) grade >= II, congestive heart failure, serious cardiac arrhythmia requiring medication.
10. Current or recent serious polyneuropathy (grade >= 1 according to NCI CTCAE v3.0 criteria; exception: absence of tendon reflexes).
11. Hemapoetic diseases.
12. Known intra-abdominal inflammatory process or serious gastrointestinal ulceration.
13. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
14. Thromboembolic events or severe hemorrhage (>= 6 months before treatment start).
15. Known hypersensitivity to oxaliplatin, the background medication (bevacizumab, FA or 5-FU) or to their compounds, incl. Chinese hamster ovary (CHO) cell proteins or other recombinant human or humanized antibodies.
16. Known Gilbert-Syndrome
17. Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational regimen or patient at high risk from treatment 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. 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 ßHCG) within 7 days before the first dose of study drug].
20. Patients who are confined by order of either judicial or administrative authorities (according to § 40 Abs. 1 S. 3 AMG).
21. Patients who are incapable to understand the aim, importance and consequences of the study and to give legal informed consent (according to § 40 Abs. 4 and § 41 Abs. 2 and Abs. 3 AMG).
22. Patients with a history of a psychological illness or condition such as to interfere with the p

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified