A Randomized Multicenter Clinical Trial for Patient With Multi-organ, Colorectal Cancer Metastases Comparing the Combination of Chemotherapy and Maximal Tumor Debulking Versus Chemotherapy Alone.
- Histological or cytological documentation of cancer is required.
- Indication for first line palliative systemic treatment for metastatic colorectal
- Patients with CRC metastases in ≥ 2 different organs and
- >3 extrahepatic metastases or
- >5 hepatic metastases not located to one lobe or
- ≥1 hepatic metastases and positive para-aortal or celiac lymph nodes or adrenal
- The primary tumor is excluded as metastatic site.
- Tumor debulking can be achieved with local treatment modalities in at least 80% of
- To meet the inclusion criteria a cytological analysis should be performed in case of
any uncertainty about the presence of a lesion e.g. a false positive or false
negative result on imaging.
- Age ³ 18 years.
- WHO performance status 0 - 1.
- Life expectancy of at least 12 weeks.
- Adequate bone marrow, liver and renal function as assessed by the following
laboratory requirements to be conducted within 7 days prior to screening:
- Hemoglobin ≥ 5.6 mmol/L;
- Absolute neutrophil count (ANC) ≥ 1,500/mm3;
- Platelet count ≥ 100*109/l;
- Total bilirubin ≤ 1.5 times the upper limit of normal;
- ALT and AST ≤ 2.5 x upper limit of normal (≤ 5 x upper limit of normal for
subjects with liver involvement of their cancer);
- Albumine > 30 g/l;
- Serum creatinine ≤ 1.5 x upper limit of normal or a MDRD ≥ 50 ml/min;
- Prothrombin time or INR < 1.5 x ULN, unless coumarin derivates are used. Due to
interactions with capecitabine, all patients using coumarin derivates will be
treated with LMWH instead.
- Activated partial thromboplastin time < 1.25 x ULN (therapeutic anticoagulation
therapy is allowed if this treatment can be interrupted as judged by the
- Written informed consent.
- Prior chemotherapy for metastatic disease.
- Prior (neo-)adjuvant chemotherapy for non-metastatic disease < 6 months after last
treatment and first detection of metastasis.
- Candidates for HIPEC.
- Patients with liver metastases only
- Evidence of brain metastases.
- Other malignant diseases
- History of cardiac disease:
- Congestive heart failure >NYHA class 2;
- Active Coronary Artery Disease (defined as myocardial infarction within 6 months
prior to screening);
- Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin
- Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of
screening on a stable antihypertensive regimen. Blood pressure must be stable on at
least 3 separate measurements on at least 2 separate days.
- Uncontrolled infections (> grade 2 NCI-CTC version 4.0).
- Pregnant or breast-feeding women. Women of childbearing potential must have a
negative pregnancy test performed within 7 days of the start of treatment. Both men
and women enrolled in this trial must agree to use adequate barrier birth control
measures (e.g., cervical cap, condom, and diaphragm) or intrauterine device during
the course of the trial. Oral birth control methods alone will not be considered
adequate on this study, because of the potential pharmacokinetic interaction between
study drug and oral contraceptives. Concomitant use of oral and barrier
contraceptives is advised.
- Concurrent anticancer chemotherapy, immunotherapy or investigational drug therapy
during the study or within 4 weeks of the start of study drug.
- Concomitant use of dexamethasone, anti-convulsants and anti-arrhythmic drugs other
than digoxin or beta blockers.
- Severe allergy for contrast media not controlled with premedication.
- Substance abuse, medical, psychological or social conditions that may interfere with
the subject's participation in the study or evaluation of the study results.
- Any condition that is unstable or could jeopardize the safety of the subject and
their compliance in the study.