Treatment Strategies in Colorectal Cancer Patients With Initially Unresectable Liver-only Metastases (CAIRO5)
Colorectal Cancer, Liver Metastases
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring Colorectal cancer, Chemotherapy, Anti-EGFR, Liver metastases, R0 R1 liver resection, Resectability of liver, Liver expert panel
Eligibility Criteria
Inclusion Criteria:
- Histological proof of colorectal cancer
- Initially unresectable metastases confined to the liver according to CT scan, obtained ≤3 weeks prior to registration. Unresectability should be confirmed by the liver expertpanel. Patients with small (≤ 1 cm) extrahepatic lesions that are not clearly suspicious of metastases are eligible
- Known mutation status of RAS and BRAF
- WHO performance status 0-1 (Karnofsky performance status ≥ 70)
- Age ≥ 18 years
- No contraindications for liver surgery
- In case of primary tumor in situ: tumor should be resectable
- In case of resected primary tumor: adequate recovery from surgery
- Adequate organ functions, as determined by normal 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 ≤ 5x ULN)
- Life expectancy > 12 weeks
- Expected adequacy of follow-up
- Written informed consent
Exclusion Criteria:
- Extrahepatic metastases, with the exception of small (≤ 1 cm) extrahepatic lesions that are not clearly suspicious of metastases
- Unresectable primary tumor
- Serious comorbidity or any other condition preventing the safe administration of study treatment (including both systemic treatment and surgery)
- Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation
- Uncontrolled hypertension, or unsatisfactory blood pressure control with ≥3 antihypertensive drugs
- Previous systemic treatment for metastatic disease; previous adjuvant treatment is allowed if completed ≥ 6 months prior to randomisation
- Previous surgery for metastatic disease
- Previous intolerance of study drugs in the adjuvant setting
- Pregnant or lactating women
- Second primary malignancy within the past 5 years with the exception of adequately treated in situ carcinoma of any organ or basal cell carcinoma of the skin, or second primary colorectal cancer.
- Any concomitant experimental treatment.
Sites / Locations
- Universitair ziekenhuis AntwerpenRecruiting
- Wilhelmina Ziekenhuis
- FlevoziekenhuisRecruiting
- Ziekenhuis Nij Smellinghe
- Medisch Centrum Leeuwarden, loc. ZuidRecruiting
- Antonius ZiekenhuisRecruiting
- Gelre ZiekenhuisRecruiting
- Rijnstate ziekenhuisRecruiting
- Gelderse Vallei
- Sint Jansdal ZiekenhuisRecruiting
- Radboud UMCRecruiting
- Streekziekenhuis Koningin BeatrixRecruiting
- Atrium Medical CenterRecruiting
- Maastricht UMC+Recruiting
- Laurentius ZiekenhuisRecruiting
- Orbis Medical CenterRecruiting
- VieCuri Medisch CentrumRecruiting
- OLVG, locatie OostRecruiting
- Jeroen Bosch ZiekenhuisRecruiting
- Bravis ZiekenhuisRecruiting
- Amphia ZiekenhuisRecruiting
- Catharina Ziekenhuis
- St. Anna Ziekenhuis
- Elkerliek ZiekenhuisRecruiting
- Bravis ZiekenhuisRecruiting
- Sint Elisabeth Ziekenhuis
- TweeSteden ZiekenhuisRecruiting
- BernhovenRecruiting
- Maxima Medisch Centrum, loc. VeldhovenRecruiting
- Medisch Centrum AlkmaarRecruiting
- Amsterdam UMC, location AMCRecruiting
- Amsterdam UMC, location VUMCRecruiting
- Antoni van LeeuwenhoekRecruiting
- BovenIJ ZiekenhuisRecruiting
- OLVG, locatie OostRecruiting
- OLVG, locatie WestRecruiting
- Rode Kruis Ziekenhuis
- Spaarne GasthuisRecruiting
- TergooiRecruiting
- Spaarne ziekenhuisRecruiting
- Westfriesgasthuis
- Waterlandziekenhuis
- Zaans Medical Center
- Deventer ZiekenhuisRecruiting
- Medisch Spectrum TwenteRecruiting
- Ziekenhuisgroep TwenteRecruiting
- Isala KliniekenRecruiting
- Meander Medisch CentrumRecruiting
- Sint Antonius ZiekenhuisRecruiting
- Admiraal de Ruyter ziekenhuisRecruiting
- Bethesda ziekenhuis
- Reinier de GraafRecruiting
- HagaziekenhuisRecruiting
- Medisch Centrum Haaglanden, WesteindeRecruiting
- Albert Schweitzer ZiekenhuisRecruiting
- Groene Hart Ziekenhuis
- LUMCRecruiting
- Erasmus MC
- Ikazia Ziekenhuis
- Maasstad ZiekenhuisRecruiting
- Sint Franciscus GasthuisRecruiting
- Franciscus VlietlandRecruiting
- UMC UtrechtRecruiting
- Treant zorggroep
- Martini ZiekenhuisRecruiting
- UMC GroningenRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Active Comparator
Experimental
Active Comparator
Arm B: FOLFOXIRI & bevacizumab (inclusion completed)
Arm A: FOLFOX/FOLFIRI & bevacizumab (inclusion completed)
Arm D: FOLFOX/FOLFIRI & panitumumab
Arm C: FOLFOX/ FOLFIRI & bevacizumab
Patients with RAS or BRAF mutated and/or right-sided tumors will receive 5FU, irinotecan, oxaliplatin (FOLFOXIRI) and bevacizumab. Intervention: FOLFOXIRI with bevacizumab
Patients with RAS or BRAF mutated and/or right-sided tumors will receive doublet fluoropyrimidine-containing chemotherapy (FOLFOX or FOLFIRI), plus bevacizumab. Intervention: FOLFOX/FOLFIRI with bevacizumab
Patients with RAS and BRAF wildtype and left-sided tumors will receive doublet fluoropyrimidine-containing chemotherapy (FOLFOX or FOLFIRI), plus panitumumab. Intervention: FOLFOX/FOLFIRI with panitumumab
Patients with RAS and BRAF wildtype and left-sided tumors will receive doublet fluoropyrimidine-containing chemotherapy (FOLFOX or FOLFIRI), plus bevacizumab. Intervention: FOLFOX/FOLFIRI with bevacizumab