| Eligibility |
Inclusion Criteria:
- Histological or cytological documentation of cancer is required.
- Indication for first line palliative systemic treatment for metastatic colorectal
cancer (mCRC).
- Patients with CRC metastases in (the primary tumor is excluded as metastatic site)
- = 2 different organs if at least >1 extra-hepatic metastases or
- = 2 different organs including >5 hepatic metastases not located to one lobe or
- = 2 different organs including either a positive para-aortal lymph nodes or
celiac lymph nodes or adrenal metastases or pleural carcinomatosis or peritoneal
carcinomatosis
- Feasible radical tumor debulking. Incomplete tumor debulking is allowed only if at
least 80% of metastases can be treated.
- 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 = 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);
- Albumin > 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 treating
physician).
- Written informed consent.
Exclusion Criteria:
- Prior (neo-)adjuvant chemotherapy for < 6 months after last treatment and first
detection of extra-hepatic metastases, except for neoadjuvant capecitabine in the
context of chemoradiation for rectal carcinoma.
- Candidates for HIPEC.
- Patients with liver metastases only
- Evidence of brain metastases.
- History of other prior malignancy except for adequately treated basal cell or squamous
cell skin cancer or in situ cervical cancer. Patients with other malignancies are
eligible if they have remained disease free for at least 5 years.- 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
are permitted).
- Uncontrolled hypertension. Blood pressure must be =160/95 mm Hg 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, anticonvulsants 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.
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