The Role of Surgery of the Primary Tumour in Patients With Synchronous Unresectable Metastases of Colorectal Cancer

Rectal Cancer Clinical Trial

— CAIRO4  

Official title:

The Role of Surgery of the Primary Tumour With Few or Absent Symptoms in Patients With Synchronous Unresectable Metastases of Colorectal Cancer, a Randomized Phase III Study. A Study of the Dutch Colorectal Cancer Group (DCCG)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01606098
• Other study ID #: CAIRO4
• Status: Completed
• Phase: Phase 3
• Start date: July 2012
• Est. completion date: December 2022

Study information

• Verified date: September 2023
• Source: Dutch Colorectal Cancer Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The clinical benefit of resection of the primary tumour in patients with synchronous unresectable metastases is not known. In the literature studies usually describe retrospective selected patients with synchronous metastases treated with or without resection of the primary tumour. All these studies are biased in patient selection and there are no prospective randomized studies on this topic. In patients with few or absent symptoms of the primary tumour, arguments both in favour and against initial resection have been presented, and therefore a randomized trial is warranted. Although recent publications suggest that resection of the primary tumour in synchronous metastasized colon cancer patients might not be necessary, this appears to be based on feasibility and not on clinical outcome. Several studies comparing large groups of patients with or without resection of the primary tumour suggest an improved survival when the primary tumour is resected. A potential benefit of resection of the primary tumour is to prevent complications of the primary tumour during chemotherapy treatment or during later stages of the disease. A recent analysis of the CAIRO and CAIRO2 data showed that metastatic colon cancer patients who had a resection of the primary tumour prior to study entry, had an improved survival compared to patients without a resection of the primary tumour. However, these patients were selected after the primary tumour was resected and therefore these results are not corrected for surgical morbidity and mortality. The investigators here propose a randomized trial in order to demonstrate that resection of the primary tumour does improve overall survival.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: December 2022
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological proof of colorectal cancer
• Resectable primary tumour in situ with unresectable distant metastases
• No indication for neo-adjuvant (chemo)radiation
• No severe signs or symptoms related to the primary tumour (i.e. severe bleeding, obstruction, severe abdominal pain) that require immediate surgery or other symptomatic treatment (e.g. stenting)
• No prior systemic treatment for advanced disease
• Age = 18 years
• WHO performance status 0-2
• Laboratory values obtained = 4 weeks prior to randomization: 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)
• Expected adequacy of follow-up
• Written informed consent
• CT scan abdomen and CT thorax/X-thorax performed = 4 weeks prior to randomization

Exclusion Criteria:

• Pregnancy, lactation
• Unresectable primary tumour (i.e. neurovascular encasement, substantial ingrowth in pancreatic head), or any condition preventing the safety or feasibility of resection of the primary tumour, i.e. massive ascites or extensive peritoneal disease
• Requirement of neoadjuvant (chmo)radiation therapy
• 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
• Any medical condition that prevents the safe administration of systemic treatment
• Previous intolerance of fluoropyrimidines, known dihydropyrimidine dehydrogenase (DPD) deficiency
• Planned radical resection of all metastatic disease
• Uncontrolled hypertension, i.e. values consistently > 150/100 mmHg
• Use of = 3 antihypertensive drugs
• Significant cardiovascular disease < 1 yr before randomization (symptomatic congestive heart failure, myocardial infarction, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, cerebro vascular event)
• Chronic active infection
• Concurrent treatment with any other anti-cancer therapy as described per protocol

Related Conditions & MeSH terms

• Colon Cancer
• Colorectal Neoplasms
• Primary Tumour
• Rectal Cancer

Intervention

Procedure:
• Surgery of the primary tumour
Surgical resection of the colon tumour

Drug:
• Systemic treatment
First line fluoropyrimidine-based chemotherapy with bevacizumab. The chemotherapy regimen is to the discretion of the local investigator, who may choose between: 5FU/LV or capecitabine or capecitabine + oxaliplatin(CAPOX)or 5FU + oxaliplatin(FOLFOX 4 or FOLFOX 7)or 5FU + irinotecan (FOLFIRI) or capecitabine + irinotecan(CAPIRI)

Locations

Country	Name	City	State
Denmark	University Hospital Aalborg	Aalborg
Denmark	Rigshospitalet	Copenhagen
Denmark	Herlev Hospital	Herlev
Denmark	Regionshospital Herning	Herning
Denmark	Roskilde hospital	Roskilde
Netherlands	Medisch Centrum Alkmaar	Alkmaar
Netherlands	Ziekenhuisgroep Twente	Almelo
Netherlands	Flevoziekenhuis	Almere
Netherlands	Ziekenhuis Amstelland	Amstelveen
Netherlands	Academic Medical Centre	Amsterdam
Netherlands	OLVG	Amsterdam
Netherlands	VUMC	Amsterdam
Netherlands	Gelre Ziekenhuis	Apeldoorn
Netherlands	Wilhelmina Ziekenhuis	Assen
Netherlands	Rode Kruis Ziekenhuis	Beverwijk
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Jeroen Bosch	Den Bosch
Netherlands	MC Haaglanden en Bronovo Nebo	Den Haag
Netherlands	Slingeland Ziekenhuis	Doetinchem
Netherlands	Albert Schweitzer Ziekenhuis	Dordrecht
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Maxima Medisch Centrum	Eindhoven
Netherlands	St Annaziekenhuis	Geldrop
Netherlands	Groene Hart Ziekenhuis	Gouda
Netherlands	Martini Ziekenhuis	Groningen
Netherlands	UMCG	Groningen
Netherlands	Spaarne Gasthuis	Haarlem
Netherlands	St Jansdal	Harderwijk
Netherlands	Elkerliek Ziekenhuis	Helmond
Netherlands	Spaarne Gasthuis	Hoofddorp
Netherlands	St Antonius Ziekenhuis	Nieuwegein
Netherlands	Radboudumc	Nijmegen
Netherlands	Waterland Ziekenhuis	Purmerend
Netherlands	Laurentius Ziekenhuis	Roermond
Netherlands	Erasmus MC	Rotterdam
Netherlands	Fransicus Gastuis & Vlietland	Rotterdam
Netherlands	Maasstad Ziekenhuis	Rotterdam
Netherlands	Antonius Ziekenhuis	Sneek
Netherlands	Ziekenhuis Rivierenland	Tiel
Netherlands	Elisabeth-Tweesteden	Tilburg
Netherlands	Bernhoven Ziekenhuis	Uden
Netherlands	University Medical Centre Utrecht	Utrecht
Netherlands	Bernhoven Ziekenhuis	Veghel
Netherlands	VieCuri Medisch Centrum	Venlo
Netherlands	Zaans Medisch Centrum	Zaandam
Netherlands	Isala Klinieken	Zwolle

Sponsors (2)

Lead Sponsor	Collaborator
Dutch Colorectal Cancer Group	Hoffmann-La Roche

Countries where clinical trial is conducted

Denmark,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Overall survival of the intent-to-treat population	Time from randomisation until death, assessed up to 5 years
Secondary	Progression-free survival		Time from randomisation until first progression or death whichever comes first, asessed up to 5 years
Secondary	Response to chemotherapy	Response rate according to RECIST 1.1	Fist-line chemotherapy, assessed until progression
Secondary	Systemic therapy related toxicity	Adverse events grade 3-4 according to NCI-CTC 4.0	Every 3 weeks during first-line treatment
Secondary	Surgery related morbidity and mortality		30 days
Secondary	Quality of life	EORTC QLQ-C30 and CR38	Every 6 months from randomisation until first progression
Secondary	Interval between randomization and initiation of systemic treatment		Number of days between randomization and initiation of systemic treatment
Secondary	Cost-benefit analyses		Until end of first-line systemic treatment
Secondary	Patients requiring resection of the primary tumour in the non-resection arm	Number of patients requiring resection of the primary tumour in the non-resection arm	Time from randomisation until death, assessed up to 5 years
Secondary	Overall survival in patients in whom treatment according to protocol was initiated	Having received at least one cycle of systemic treatment in arm A and surgery in arm B	Time form randomisation until death, assessed up to 5 years

External Links

•   Dutch Colorectal Cancer Group