Maintenance Treatment Versus Observation After Induction in Advanced Colorectal Carcinoma (CAIRO3)

This is an interventional treatment trial for Colorectal Cancer Metastatic focused on measuring CAIRO3, DCCG, colorectal cancer, induction, metronomic chemotherapy, observation, capecitabine, bevacizumab, oxaliplatin Read More

Before the start of induction therapy:

Inclusion Criteria:

• Histological proof of colorectal cancer (in case of a single metastasis, histological or cytological proof of this lesion should be obtained);
• Distant metastases (patients with only local recurrence are not eligible);
• Unidimensionally measurable disease (> 1 cm on spiral CT scan or > 2 cm on chest X-ray; liver ultrasound is not allowed). Serum CEA may not be used as a parameter for disease evaluation;
• In case of previous radiotherapy, at least one measurable lesion should be located outside the irradiated field.
• Ongoing or planned first line treatment with 6 cycles of Xeloda, Eloxatin, and Avastin.

Exclusion criteria

• Prior adjuvant treatment for stage II/III colorectal cancer ending within 6 months before the start of induction treatment
• Any prior adjuvant treatment after resection of distant metastases
• Previous systemic treatment for advanced disease

At randomisation:

Inclusion criteria:

• WHO performance status 0-1 (Karnofsky PS > 70%);
• Disease evaluation with proven SD, PR or CR according to RECIST after 6 cycles of MTD chemotherapy performed in week 3-4 of the 6th cycle induction therapy, and randomisation performed in week 3-5 of the 6th cycle (see time table);
• Laboratory values obtained ≤ 2 weeks prior to randomisation: adequate bone marrow function (Hb > 6.0 mmol/L, absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L), renal function (serum creatinine ≤ 1.5x ULN and creatinine clearance, Cockroft formula, > 30 ml/min), liver function (serum bilirubin ≤ 2 x ULN, serum transaminases ≤ 3 x ULN without presence of liver metastases or ≤ 5x ULN with presence of liver metastases);
• Life expectancy > 12 weeks;
• Age >= 18 yrs;
• Negative pregnancy test in women with childbearing potential;
• Expected adequacy of follow-up;
• Institutional Review Board approval;
• Written informed consent Exclusion criteria
• History or clinical signs/symptoms of CNS metastases;
• History of a second malignancy ≤ 5 years with the exception of adequately treated carcinoma of cervix or basal/squamous cell carcinoma of skin;
• Previous intolerance of XelodaR, EloxatinR, and/or AvastinR for which any of these drugs have been permanently discontinued; patients with previous dose reductions or delays are eligible; patients with grade 2 neurotoxicity after the 6th cycle are eligible, and retreatment with EloxatinR after PFS1 should depend on the grade of neurotoxicity at that moment;
• Known dihydropyrimidine dehydrogenase (DPD) deficiency;
• (Planned) radical resection of all metastatic disease;
• Uncontrolled hypertension, i.e. consistently > 150/100 mmHg;
• Use of more than 3 antihypertensive drugs;
• Significant cardiovascular disease < 1 yr before randomisation (symptomatic congestive heart failure, myocardial ischemia or infarction, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, arterial thrombosis, cerebrovascular event, pulmonary embolism);
• Any of these significant cardiovascular events during previous fluoropyrimidine therapy;
• Chronic active infection;
• Any other concurrent severe or uncontrolled disease preventing the safe administration of study drugs;
• Any impairment of gastrointestinal function or -disease that may significantly impair the absorption of oral drugs (i.e. uncontrolled nausea, vomiting, diarrhoea (defined as >CTC grade 2), malabsorption syndrome, bowel obstruction, or inability to swallow tablets);
• Concomitant treatments: concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation; concurrent treatment with any other anti-cancer therapy; full-dose anticoagulation (is allowed if started during induction therapy);
• Continuous use of immunosuppressive agents (except the use of corticosteroids as anti-emetic prophylaxis/treatment).