Clinical trial NCT02015923: Resection vs no Resection of the Primary in Colorectal Cancer With Unresectable Metastases
Official title: Multicenter Randomized Study in Patients With Colorectal Cancer With Unresectable Metastases. Impact of Resection vs no Resection of the Primary Tumour as a Survival Factor
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Colonic Cancer
Unresectable Metastasis Originating in Colonic Cancer
Keywords: Colonic cancer
Metastasis
Lead sponsor: Hospital Universitari de Bellvitge
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
First posted: 2013-12-19
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Main outcome: Assess the impact of cancer-related survival at 2 years in patients with unresectable metastatic colorectal cancer treated with chemotherapy alone versus surgery followed by chemotherapy. To assess overall survival. To evaluate postoperative morbidity and mortality in patients treated with resection of the primary tumor. Assess complications and meed for surgery in patients treated with systemic chemotherapy only during the course of the disease. Identify and describe the complications related to chemotherapy and toxicity in the short and medium term systemic treatment. Assessing the quality of life questionnaire QLQ-C30 and QLQ-CR29. To study prognostic survival factors.

Method: multicenter randomized clinical trail (22 hospitals). Two parallel group in which to evaluate two therapeutic strategies for colorectal cancer metastasis unresectable stage IV: chemotherapy alone versus primary tumor resection plus chemotherapy.

Subjects: patients with unresectable nonmetastatic colorectal cancer. Hypothesis:Surgical resection of the primary tumor in stage IV colorectal patients with unresectable synchronous metastases increases by 14% overall survival compared to patients receiving systemic treatment with chemotherapy without resection of the primary tumor (survival of 34% vs 20%).

Detailed description: Intervention: Arm B (control): chemotherapy alone, regimen according to each center. Arm A (experimental): surgery (complete tumoral resection; R0) followed by chemotherapy, regimen according to each center. Statistical Analysis: A power analysis showed that to assure a significance level of 0,05 and a beta error 0.20. 168 patients are necessary in each arm. It has been estimated a loss rate of up to 10%.

Differences between groups will be analyzed by t, U, X2, exact test and survival will be assessed according to Kaplan and Meier method. Evaluation of safety of the trial will be made in the middle of the study statistically

Eligibility criteria: Inclusion Criteria:

* colorectal cancer above to 12 cm from the anal verge
* unresectable synchronous metastases
* no contraindications for chemotherapy
* absence of peritoneal carcinomatosis, central nervous system o bone metastasis.
* performance status ECOG ≤ 2 (Eastern Cooperative Oncology Group)
* uncontrolled concomitant medical conditions that may compromise to chemotherapy
* significant symptomatic cardiac disease
* not pregnancy or breastfeeding

Exclusion Criteria:

* Cases of rectal tumours below 12cm from anal verge, or locally advanced tumours invading blood vessels, nerves or bone.
* Multiple bone metastasis or central nervous system metastasis
* Other neoplastic disease in the 5 previous years, except squamous or basal cell skin carcinoma or cervical "in situ" carcinoma
* Significant heart disease (chronic congestive heart failure, symptomatic coronary disease) or myocardial infarction in the previous 6 months
* Peripheral neuropathy
* Patients who do not give informed consent

Primary outcomes:
measure: Assess the impact of overall survival in patients with unresectable metastatic colorectal cancer treated with chemotherapy alone vs surgery followed by chemotherapy.
timeFrame: up to 2 years
Secondary outcomes:
measure: Postoperative morbidity and mortality.
timeFrame: 30 days postoperatively
measure: Complications in patients treated with systemic chemotherapy
timeFrame: up to 2 years
measure: Questionnaire Quality of life CR29
timeFrame: up to 2 years
measure: Study of possible survival factors
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Vitoria/Gasteiz
country: Spain
facility: Hospital Universitario Araba
state: Araba
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Sabadell
country: Spain
facility: Corporació Sanitària Parc Taulí
state: Barcelona
city: Sant Joan Despí
country: Spain
facility: Hospital Moisès Broggi
state: Barcelona
city: Alcazar de San Juan
country: Spain
facility: Complejo Hospitalario La Mancha Centro
state: Ciudad Real
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: Vigo
country: Spain
facility: Complejo Hospitalario Universitario de Vigo
state: Pontevedra
city: Almería
country: Spain
facility: Complejo Hospitalario Torrecárdenas
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Univesitari Vall d'Hebron
city: Donostia
country: Spain
facility: Hospital Universitario Donostia
city: Girona
country: Spain
facility: Hospital Universitari de Girona DrJosep Trueta
city: Madrid
country: Spain
facility: Hospital Univerisitario La Paz
city: Murcia
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
city: Ourense
country: Spain
facility: Complejo Hospitalario Universitario de Orense
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital General de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic la Fe
city: Zaragoza
country: Spain
facility: Hospital Clínico Univeristario "Lozano Blesa"
Study officials:
affiliation: Hospital Universitari de Bellvitge
name: Sebastiano Biondo, Sponsor
role: STUDY_CHAIR
affiliation: Hospital Universitario La Fe
name: Javier Vaqué
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital General Universitario de Valencia
name: Juan García Armengol
role: PRINCIPAL_INVESTIGATOR
affiliation: Corporacion Parc Tauli
name: Laura Mora
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitari Gemans Tiras i Pujol
name: Ignasi Camps Ausàs
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Univesitari del Mar
name: Miguel Pera Román
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Eduardo Targarona Soler
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Sant Joan Despí Moisès Broggi
name: Lorenzo Viso Pons
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínico Univeristario "Lozano Blesa"
name: José Manuel Ramírez Rodríguez
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitari de Girona DrJosep Trueta
name: David Julià Bergkvist
role: PRINCIPAL_INVESTIGATOR
affiliation: Complejo Hospitalario Universitario de Vigo
name: Teresa García Martínez
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Univerisitario La Paz
name: Mario Álvarez Gallego
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Donostia
name: José María Enríquez Navascués
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospitales Universitarios Virgen del Rocío
name: Fernando de la Portilla de Juan
role: PRINCIPAL_INVESTIGATOR
affiliation: Complejo Hospitalario de Navarra
name: Miguel Angel Ciga
role: PRINCIPAL_INVESTIGATOR
affiliation: hospital Universitari de la Vall D'Hebron
name: Eloy Espín Basany
role: PRINCIPAL_INVESTIGATOR
affiliation: Complejo Hospitalario Torrecárdenas
name: Manuel Ferrer Márquez
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Virgen de la Arrixaca
name: Jesús Abrisqueta Carrión
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Araba
name: José Errasti Alustiza
role: PRINCIPAL_INVESTIGATOR
affiliation: Complejo Hospitalario Universitario de Orense
name: Alberto Parajó Calvo
role: PRINCIPAL_INVESTIGATOR
affiliation: Complejo Hospitalario La Mancha Centro
name: Carlos Moreno Sanz
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínico Universitario de Valencia
name: Alejando Espí Macías
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitari de Bellvitge
name: Ricard Frago Montanuy
role: PRINCIPAL_INVESTIGATOR
References:
citation: Biondo S, Frago R, Kreisler E, Espin-Basany E; Spanish CR4 Group. Impact of resection versus no resection of the primary tumor on survival in patients with colorectal cancer and synchronous unresectable metastases: protocol for a randomized multicenter study (CR4). Int J Colorectal Dis. 2017 Jul;32(7):1085-1090. doi: 10.1007/s00384-017-2827-3. Epub 2017 May 11.