Table 1.

Ongoing randomized trials about primary tumor resection in metastatic CRC.

Study (ClinicalTrials.gov ID)	Phase	Main Inclusion Criteria	Estimated Enrollment	Study Start Date-Status	Primary Endpoint	Secondary Endpoint	Active Comparator	Experimental Arm
China, Guangdong (NCT02149784)	3	Colon cancer or rectal cancer with at least 12 cm far away from anal verge with unresectable metastases. No evidence of obstruction, bleeding or perforation. Pts must respond to 1st line CT.	480	September 2015   Recruiting	3-years OS	Number of pts with AEs both in surgery group and CT group.	Unresectable mCRC pts responders to CT will continue with CT	Unresectable mCRC pts responders to CT will receive surgical resection of PT
China, Shanghai (NCT02291744)	2	Colon cancer adenocarcinoma. Primary and metastatic tumors exist at the same time, and distant metastases are not resectable. No need of surgery for perforation, bleeding or obstruction. No uncontrollable large pleural or peritoneal effusion. No brain metastases.	130	October 2014   Recruiting	TFS	None.	8 cycles of XELOX	8 cycles of XELOX plus surgery
CAIRO4 (NCT01606098)   Denmark and Netherlands, multicenter	3	Resectable PT in situ (CRC) with unresectable distant metastases. No indication for neo-adjuvant (chemo)radiation. No signs or symptoms PT-related that require immediate intervention (i.e., surgery, stenting, systemic therapy or radiotherapy). No condition preventing the safety or feasibility of resection of the PT (i.e., massive ascites or extensive peritoneal disease).	360	July 2012   Active, no longer recruiting	OS	PFS. RR. G3-4 CT-related toxicity. Surgery-related morbidity and mortality. QoL. Interval between randomization and initiation of CT. Cost-benefit analyses. Pts requiring resection of PT in the non-resection arm.	1st line FP-based CT with bevacizumab	PT resection followed by 1st line FP-based CT with bevacizumab
GRECCAR 8 (NCT02314182)   France, multicenter	3	Rectal adenocarcinoma (<15 cm from the anal verge) with few or no symptoms and unresectable synchronous metastasis not amenable to curative treatment. No known unresectable PT (with clear margin > 1 mm) on imaging. No PD under CT (for at least 4 cycles). Assessment of KRAS status. No peritoneal carcinomatosis.	290	November 2014   Completed (trial end date: 27 February 2018): no longer recruiting	OS	PFS. QoL. Toxicity of CT. RR. Time to PD. Postoperative morbidity.	Continued systemic CT ± target therapy	Immuno-nutrition, PT resection + systemic CT ± target therapy
CLIMAT-PRODIGE 30 (NCT02363049)   France	3	Colon adenocarcinoma (≥15 cm from the anal verge) Uncomplicated PT. No known unresectable PT on imaging. Unresectable synchronous liver metastases. No extra-hepatic metastatic disease.	278	July 2014   Recruiting	OS	QoL Postoperative complications. PFS. TTP. Rate of secondary curative resection (R0).	CT ± targeted therapy alone	Surgery followed by CT ± targeted therapy

AEs: adverse events; CT: chemotherapy; FP: fluoropyrimidine; mCRC: metastatic colorectal cancer; OS: overall survival; PD: progression of disease; PFS: progression-free survival; PT: primary tumor; pts: patients; QoL: quality of life; R0: complete tumoral resection; RR: response rate; TFS: time of failure of strategy (the second progression time after induction therapy, time to the use of second line strategy (if no reapplication of induction therapy) or time to no further treatment); TTP: time to metastatic progression; XELOX: capecitabine/oxaliplatin.