FOLFOX Plus SIR-SPHERES MICROSPHERES Versus FOLFOX Alone in Patients With Liver Mets From Primary Colorectal Cancer (SIRFLOX)

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ClinicalTrials.gov Identifier: NCT00724503

Recruitment Status : Completed

First Posted : July 29, 2008

Results First Posted : March 26, 2019

Last Update Posted : March 26, 2019

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Sponsor:

Information provided by (Responsible Party):

Sirtex Medical

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Colorectal Cancer Colorectal Carcinoma Liver Metastases
Interventions	Device: SIR-Spheres yttrium-90 microspheres Drug: Systemic chemotherapy (FOLFOX)
Enrollment	530

Participant Flow

Recruitment Details	Between 10 October 2006 and 26 April 2013, 561 patients were screened. 31 screen failures included 2 patients who were randomized twice. 530 patients were randomized in the Intent to treat (ITT) population from 87 centres in Australia, Europe including Belgium, France, Germany, Israel, Italy and Spain, New Zealand and the US.
Pre-assignment Details


Arm/Group Title	mFOLFOX6 Plus SIRT	mFOLFOX6 Alone
Arm/Group Description	A single injection of SIR-Spheres m...	systemic chemotherapy consisting of...
Arm/Group Description	A single injection of SIR-Spheres microspheres into the liver plus systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)	systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)
Period Title: Overall Study
Started	267	263
Completed	57	43
Not Completed	210	220
Reason Not Completed
Lost to Follow-up	4	8
Withdrawal by Subject	11	23
Death	190	182
Adverse Event	1	0
Not otherwise specified	4	7

Baseline Characteristics

Arm/Group Title		mFOLFOX6 Plus SIRT	mFOLFOX6 Alone	Total
Arm/Group Description		A single injection of SIR-Spheres m...	Systemic chemotherapy consisting of...	Total of all reporting groups
Arm/Group Description		A single injection of SIR-Spheres microspheres into the liver plus systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)	Systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)	Total of all reporting groups
Overall Number of Baseline Participants		267	263	530
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous ^[1] Median (Full Range) Unit of measure: Years
	Number Analyzed	267 participants	262 participants	529 participants
		63 (28 to 81)	63 (23 to 89)	63 (23 to 89)
		[1] Measure Analysis Population Description: Age was unknown for 1 patient as patient withdrew consent and records
Sex: Female, Male ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	267 participants	262 participants	529 participants
	Female	85 31.8%	88 33.6%	173 32.7%
	Male	182 68.2%	174 66.4%	356 67.3%
		[1] Measure Analysis Population Description: Sex was unknown for 1 patient as patient withdrew consent and records
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	267 participants	263 participants	530 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	7 2.6%	3 1.1%	10 1.9%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 0.7%	8 3.0%	10 1.9%
	White	248 92.9%	243 92.4%	491 92.6%
	More than one race	4 1.5%	4 1.5%	8 1.5%
	Unknown or Not Reported	6 2.2%	5 1.9%	11 2.1%
WHO performance status ^[1] Measure Type: Number Unit of measure: Participants
0	Number Analyzed	267 participants	263 participants	530 participants
0		176	175	351
1	Number Analyzed	267 participants	263 participants	530 participants
1		90	87	177
Unknown	Number Analyzed	267 participants	263 participants	530 participants
Unknown		1	1	2
		[1] Measure Description: WHO performance status: (0) Able to carry out all normal activity without restriction (1) Restricted in physically strenuous activity but ambulatory and able to carry out light work
Primary tumor in situ Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	267 participants	263 participants	530 participants
	No	148 55.4%	141 53.6%	289 54.5%
	Yes	119 44.6%	121 46.0%	240 45.3%
	Unknown	0 0.0%	1 0.4%	1 0.2%
Extra-hepatic metastases at randomization Measure Type: Number Unit of measure: Participants
No	Number Analyzed	267 participants	263 participants	530 participants
No		160	159	319
Yes	Number Analyzed	267 participants	263 participants	530 participants
Yes		107	104	211
Tumor liver involvement % Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	267 participants	263 participants	530 participants
	<=25%	185 69.3%	192 73.0%	377 71.1%
	>25%	81 30.3%	70 26.6%	151 28.5%
	Unknown	1 0.4%	1 0.4%	2 0.4%
Synchronous metastases Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	267 participants	263 participants	530 participants
		241 90.3%	233 88.6%	474 89.4%

Outcome Measures

1.Primary Outcome


Title	Progression-Free Survival (PFS) at Any Site
Description	PFS defined using Response Evaluation Criteria In Solid Tumors Criteri...
Description	PFS defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as an increase in the sum of the longest diameters of ≥ 20% and an absolute increase in the sum of the longest diameters of ≥ 5 mm, or the appearance of a new lesion.
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Outcome Measure Data

Analysis Population Description

ITT population


Arm/Group Title	mFOLFOX6 Plus SIRT	mFOLFOX6 Alone
Arm/Group Description:	A single injection of SIR-Spheres m...	Systemic chemotherapy consisting of...
Arm/Group Description:	A single injection of SIR-Spheres microspheres into the liver plus systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)	Systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)
Overall Number of Participants Analyzed	267	263
Median (95% Confidence Interval) Unit of Measure: Months
	10.7 (9.9 to 11.4)	10.2 (9.4 to 11.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	mFOLFOX6 Plus SIRT, mFOLFOX6 Alone
	Comments	The null hypothesis tested for the primary efficacy endpoint is rate of progression (months) of SIRT/FOLFOX treatment versus FOLFOX is equal for both groups. The two-sided alternative hypothesis tested with 95% confidence is PFS rate for SIRT/FOLFOX treatment lower to that of FOLFOX.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.551
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95% 0.77 to 1.12
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Percentage of Participants With Overall Response
Description	Tumour Response Rate per Response Evaluation Criteria In Solid Tumors ...
Description	Tumour Response Rate per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR) - Disappearance of all target lesions which is confirmed if determined by two observations not less than 4 weeks apart; Partial Response (PR) - >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Through study completion, up to 60 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	B: FOLFOX + SIR-Spheres	A: FOLFOX Alone
Arm/Group Description:	A single injection of SIR-Spheres m...	Systemic chemotherapy consisting of...
Arm/Group Description:	A single injection of SIR-Spheres microspheres into the liver plus systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX) SIR-Spheres yttrium-90 microspheres: SIR-Spheres microspheres implanted once on the 3rd or 4th day of the first week of the first chemotherapy cycle Systemic chemotherapy (FOLFOX): Oxaliplatin 60 mg/m2,IV infusion, q two weeks for first 3 cycles Oxaliplatin 85 mg/m2, IV infusion, q two weeks from cycle 4 onwards Leucovorin 200 mg/m2, IV infusion, q two weeks 5-Fluorouracil 400 mg/m2, IV bolus, q two weeks 5-Fluorouracil 2.4 g/m2, IV infusion, q two weeks	Systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5- Fluorouracil (FOLFOX) Systemic chemotherapy (FOLFOX): Oxaliplatin 85 mg/m2, IV infusion, q two weeks Leucovorin 200 mg/m2, IV infusion, q two weeks 5-Fluorouracil 400 mg/m2, IV bolus, q two weeks 5-Fluorouracil 2.4 g/m2, IV infusion, q two weeks
Overall Number of Participants Analyzed	267	263
Measure Type: Number Unit of Measure: percentage of participants
	76.4	68.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	B: FOLFOX + SIR-Spheres, A: FOLFOX Alone
	Comments	A sample size of at least 450 patients for the SIRFLOX study was estimated to be needed to detect an increase in the median PFS at any site from 9.4 months to 12.5 months with 80% power and 95% confidence. Taking into account the number of patients who might receive the alternative treatment or lack of imaging data, the sample size was increased to 530. The Null hypothesis is no difference between the treatment arms with respect to PFS.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.05
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	From consent until 28 days post last dose of protocol chemotherapy.
Adverse Event Reporting Description	Adverse Events monitored for all participants who were randomized and received at least 1 cycle of study treatment. Of the 267 in 'mFOLFOX6 Plus SIRT' arm, 18 switched study treatment arms and 3 did not get any treatment. Hence safety population in this arm comprises 246 participants. The 'mFOLFOX6 alone' arm includes the initial 263 plus 18 that switched over. 11 did not receive any treatment. Hence safety population in this arm comprises 270 participants.

Arm/Group Title	mFOLFOX6 Plus SIRT	mFOLFOX6 Alone
Arm/Group Description	A single injection of SIR-Spheres m...	systemic chemotherapy consisting of...
Arm/Group Description	A single injection of SIR-Spheres microspheres into the liver plus systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)	systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)
All-Cause Mortality
	mFOLFOX6 Plus SIRT	mFOLFOX6 Alone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	190/246 (77.24%)	182/270 (67.41%)
Serious Adverse Events Serious Adverse Events
	mFOLFOX6 Plus SIRT	mFOLFOX6 Alone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	134/246 (54.47%)	112/270 (41.48%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/246 (0.41%)	4/270 (1.48%)
Febrile Neutropenia ^† 1	13/246 (5.28%)	4/270 (1.48%)
Heparin-Induced Thrombocytopenia ^† 1	0/246 (0.00%)	1/270 (0.37%)
Neutropenia ^† 1	3/246 (1.22%)	2/270 (0.74%)
Splenic Infarction ^† 1	0/246 (0.00%)	1/270 (0.37%)
Thrombocytopenia ^† 1	1/246 (0.41%)	1/270 (0.37%)
Cardiac disorders
Acute Coronary Syndrome ^† 1	1/246 (0.41%)	0/270 (0.00%)
Acute Myocardial Infarction ^† 1	2/246 (0.81%)	2/270 (0.74%)
Angina Pectoris ^† 1	1/246 (0.41%)	1/270 (0.37%)
Arrhythmia ^† 1	0/246 (0.00%)	1/270 (0.37%)
Arteriospasm Coronary ^† 1	1/246 (0.41%)	0/270 (0.00%)
Atrial Fibrillation ^† 1	1/246 (0.41%)	0/270 (0.00%)
Atrial Flutter ^† 1	1/246 (0.41%)	0/270 (0.00%)
Atrioventricular Block Complete ^† 1	0/246 (0.00%)	1/270 (0.37%)
Cardiac Arrest ^† 1	0/246 (0.00%)	1/270 (0.37%)
Cardiac Failure ^† 1	1/246 (0.41%)	1/270 (0.37%)
Intracardiac Thrombus ^† 1	1/246 (0.41%)	0/270 (0.00%)
Myocardial Infarction ^† 1	1/246 (0.41%)	0/270 (0.00%)
Stress Cardiomyopathy ^† 1	0/246 (0.00%)	1/270 (0.37%)
Supraventricular Tachycardia ^† 1	0/246 (0.00%)	1/270 (0.37%)
Congenital, familial and genetic disorders
Hydrocele ^† 1	1/246 (0.41%)	0/270 (0.00%)
Ear and labyrinth disorders
Vertigo ^† 1	0/246 (0.00%)	1/270 (0.37%)
Gastrointestinal disorders
Abdominal Pain ^† 1	11/246 (4.47%)	5/270 (1.85%)
Abdominal Pain Upper ^† 1	4/246 (1.63%)	1/270 (0.37%)
Anal Fissure ^† 1	0/246 (0.00%)	2/270 (0.74%)
Anal Inflammation ^† 1	0/246 (0.00%)	1/270 (0.37%)
Ascites ^† 1	4/246 (1.63%)	0/270 (0.00%)
Constipation ^† 1	10/246 (4.07%)	7/270 (2.59%)
Diarrhoea ^† 1	11/246 (4.47%)	8/270 (2.96%)
Duodenal Ulcer ^† 1	3/246 (1.22%)	1/270 (0.37%)
Duodenal Ulcer Haemorrhage ^† 1	0/246 (0.00%)	1/270 (0.37%)
Duodenitis ^† 1	2/246 (0.81%)	0/270 (0.00%)
Erosive Oesophagitis ^† 1	1/246 (0.41%)	0/270 (0.00%)
Gastric Haemorrhage ^† 1	1/246 (0.41%)	0/270 (0.00%)
Gastric Ulcer ^† 1	6/246 (2.44%)	0/270 (0.00%)
Gastritis ^† 1	4/246 (1.63%)	0/270 (0.00%)
Gastritis Atrophic ^† 1	1/246 (0.41%)	0/270 (0.00%)
Gastritis Erosive ^† 1	0/246 (0.00%)	1/270 (0.37%)
Gastroduodenitis ^† 1	1/246 (0.41%)	0/270 (0.00%)
Gastrointestinal Haemorrhage ^† 1	5/246 (2.03%)	1/270 (0.37%)
Haematemesis ^† 1	2/246 (0.81%)	0/270 (0.00%)
Haemorrhoidal Haemorrhage ^† 1	0/246 (0.00%)	1/270 (0.37%)
Haemorrhoids ^† 1	0/246 (0.00%)	1/270 (0.37%)
Ileus ^† 1	0/246 (0.00%)	1/270 (0.37%)
Intestinal Haematoma ^† 1	0/246 (0.00%)	1/270 (0.37%)
Intestinal Obstruction ^† 1	4/246 (1.63%)	6/270 (2.22%)
Intestinal Perforation ^† 1	2/246 (0.81%)	3/270 (1.11%)
Large Intestinal Obstruction ^† 1	2/246 (0.81%)	2/270 (0.74%)
Large Intestinal Stenosis ^† 1	1/246 (0.41%)	0/270 (0.00%)
Large Intestine Perforation ^† 1	1/246 (0.41%)	1/270 (0.37%)
Melaena ^† 1	1/246 (0.41%)	1/270 (0.37%)
Nausea ^† 1	8/246 (3.25%)	4/270 (1.48%)
Oesophageal Ulcer ^† 1	1/246 (0.41%)	0/270 (0.00%)
Oesophageal Varices Haemorrhage ^† 1	1/246 (0.41%)	1/270 (0.37%)
Oesophagitis ^† 1	1/246 (0.41%)	0/270 (0.00%)
Oesophagitis Haemorrhagic ^† 1	0/246 (0.00%)	1/270 (0.37%)
Oral Pain ^† 1	0/246 (0.00%)	1/270 (0.37%)
Pancreatitis ^† 1	3/246 (1.22%)	0/270 (0.00%)
Proctalgia ^† 1	1/246 (0.41%)	1/270 (0.37%)
Rectal Haemorrhage ^† 1	3/246 (1.22%)	2/270 (0.74%)
Rectal Stenosis ^† 1	0/246 (0.00%)	1/270 (0.37%)
Small Intestinal Obstruction ^† 1	1/246 (0.41%)	0/270 (0.00%)
Stomatitis ^† 1	3/246 (1.22%)	0/270 (0.00%)
Volvulus Of Small Bowel ^† 1	0/246 (0.00%)	1/270 (0.37%)
Vomiting ^† 1	16/246 (6.50%)	3/270 (1.11%)
General disorders
Asthenia ^† 1	3/246 (1.22%)	1/270 (0.37%)
Chest Pain ^† 1	3/246 (1.22%)	0/270 (0.00%)
Chills ^† 1	1/246 (0.41%)	0/270 (0.00%)
Device Dislocation ^† 1	0/246 (0.00%)	1/270 (0.37%)
Device Occlusion ^† 1	0/246 (0.00%)	2/270 (0.74%)
Extravasation ^† 1	0/246 (0.00%)	1/270 (0.37%)
Fatigue ^† 1	4/246 (1.63%)	0/270 (0.00%)
General Physical Health Deterioration ^† 1	1/246 (0.41%)	2/270 (0.74%)
Hernia ^† 1	1/246 (0.41%)	0/270 (0.00%)
Influenza Like Illness ^† 1	1/246 (0.41%)	0/270 (0.00%)
Infusion Site Pain ^† 1	0/246 (0.00%)	1/270 (0.37%)
Malaise ^† 1	1/246 (0.41%)	0/270 (0.00%)
Oedema Peripheral ^† 1	1/246 (0.41%)	0/270 (0.00%)
Pain ^† 1	1/246 (0.41%)	0/270 (0.00%)
Pyrexia ^† 1	17/246 (6.91%)	12/270 (4.44%)
Hepatobiliary disorders
Bile Duct Obstruction ^† 1	0/246 (0.00%)	1/270 (0.37%)
Bile Duct Stone ^† 1	0/246 (0.00%)	1/270 (0.37%)
Cholangitis ^† 1	2/246 (0.81%)	1/270 (0.37%)
Cholecystitis ^† 1	1/246 (0.41%)	2/270 (0.74%)
Cholecystitis Acute ^† 1	1/246 (0.41%)	0/270 (0.00%)
Cholelithiasis ^† 1	0/246 (0.00%)	1/270 (0.37%)
Gallbladder Perforation ^† 1	1/246 (0.41%)	0/270 (0.00%)
Hepatic Failure ^† 1	3/246 (1.22%)	0/270 (0.00%)
Hepatic Fibrosis ^† 1	1/246 (0.41%)	0/270 (0.00%)
Hepatic Infarction ^† 1	1/246 (0.41%)	0/270 (0.00%)
Hepatic Pain ^† 1	0/246 (0.00%)	1/270 (0.37%)
Hyperbilirubinaemia ^† 1	1/246 (0.41%)	1/270 (0.37%)
Jaundice ^† 1	1/246 (0.41%)	1/270 (0.37%)
Jaundice Cholestatic ^† 1	2/246 (0.81%)	1/270 (0.37%)
Immune system disorders
Drug Hypersensitivity ^† 1	1/246 (0.41%)	1/270 (0.37%)
Infections and infestations
Abdominal Wall Infection ^† 1	1/246 (0.41%)	0/270 (0.00%)
Abscess Limb ^† 1	1/246 (0.41%)	1/270 (0.37%)
Acute Sinusitis ^† 1	0/246 (0.00%)	1/270 (0.37%)
Anorectal Infection ^† 1	1/246 (0.41%)	0/270 (0.00%)
Campylobacter Gastroenteritis ^† 1	0/246 (0.00%)	1/270 (0.37%)
Catheter Site Infection ^† 1	0/246 (0.00%)	1/270 (0.37%)
Device Related Infection ^† 1	2/246 (0.81%)	0/270 (0.00%)
Diverticulitis ^† 1	0/246 (0.00%)	1/270 (0.37%)
Escherichia Bacteraemia ^† 1	1/246 (0.41%)	0/270 (0.00%)
Gastroenteritis ^† 1	5/246 (2.03%)	0/270 (0.00%)
Gastroenteritis Salmonella ^† 1	1/246 (0.41%)	0/270 (0.00%)
Infection ^† 1	2/246 (0.81%)	1/270 (0.37%)
Influenza ^† 1	0/246 (0.00%)	1/270 (0.37%)
Infusion Site Infection ^† 1	1/246 (0.41%)	2/270 (0.74%)
Klebsiella Sepsis ^† 1	0/246 (0.00%)	1/270 (0.37%)
Liver Abscess ^† 1	2/246 (0.81%)	0/270 (0.00%)
Lobar Pneumonia ^† 1	1/246 (0.41%)	0/270 (0.00%)
Lower Respiratory Tract Infection ^† 1	1/246 (0.41%)	0/270 (0.00%)
Lung Infection ^† 1	1/246 (0.41%)	0/270 (0.00%)
Neutropenic Infection ^† 1	2/246 (0.81%)	2/270 (0.74%)
Neutropenic Sepsis ^† 1	1/246 (0.41%)	1/270 (0.37%)
Oesophageal Candidiasis ^† 1	1/246 (0.41%)	0/270 (0.00%)
Pelvic Abscess ^† 1	0/246 (0.00%)	1/270 (0.37%)
Perihepatic Abscess ^† 1	2/246 (0.81%)	0/270 (0.00%)
Peritonitis ^† 1	3/246 (1.22%)	0/270 (0.00%)
Pneumonia ^† 1	3/246 (1.22%)	4/270 (1.48%)
Salmonellosis ^† 1	0/246 (0.00%)	1/270 (0.37%)
Sepsis ^† 1	1/246 (0.41%)	3/270 (1.11%)
Subcutaneous Abscess ^† 1	1/246 (0.41%)	0/270 (0.00%)
Upper Respiratory Tract Infection ^† 1	1/246 (0.41%)	2/270 (0.74%)
Urinary Tract Infection ^† 1	0/246 (0.00%)	1/270 (0.37%)
Wound Infection ^† 1	1/246 (0.41%)	0/270 (0.00%)
Injury, poisoning and procedural complications
Anastomotic Complication ^† 1	0/246 (0.00%)	1/270 (0.37%)
Anastomotic Leak ^† 1	0/246 (0.00%)	1/270 (0.37%)
Contrast Media Reaction ^† 1	0/246 (0.00%)	1/270 (0.37%)
Fall ^† 1	1/246 (0.41%)	2/270 (0.74%)
Femoral Neck Fracture ^† 1	1/246 (0.41%)	0/270 (0.00%)
Gastroenteritis Radiation ^† 1	1/246 (0.41%)	1/270 (0.37%)
Hip Fracture ^† 1	1/246 (0.41%)	0/270 (0.00%)
Pelvic Fracture ^† 1	1/246 (0.41%)	0/270 (0.00%)
Post Embolisation Syndrome ^† 1	2/246 (0.81%)	0/270 (0.00%)
Post Procedural Bile Leak ^† 1	2/246 (0.81%)	0/270 (0.00%)
Post Procedural Complication ^† 1	0/246 (0.00%)	1/270 (0.37%)
Post Procedural Diarrhoea ^† 1	0/246 (0.00%)	1/270 (0.37%)
Procedural Complication ^† 1	1/246 (0.41%)	0/270 (0.00%)
Procedural Pain ^† 1	2/246 (0.81%)	0/270 (0.00%)
Radiation Hepatitis ^† 1	2/246 (0.81%)	0/270 (0.00%)
Rib Fracture ^† 1	0/246 (0.00%)	1/270 (0.37%)
Spinal Fracture ^† 1	0/246 (0.00%)	1/270 (0.37%)
Subdural Haematoma ^† 1	0/246 (0.00%)	1/270 (0.37%)
Toxicity To Various Agents ^† 1	0/246 (0.00%)	1/270 (0.37%)
Vascular Procedure Complication ^† 1	1/246 (0.41%)	0/270 (0.00%)
Wound Evisceration ^† 1	0/246 (0.00%)	1/270 (0.37%)
Investigations
Alanine Aminotransferase Increased ^† 1	1/246 (0.41%)	0/270 (0.00%)
Aspartate Aminotransferase Increased ^† 1	1/246 (0.41%)	0/270 (0.00%)
Blood Albumin Decreased ^† 1	1/246 (0.41%)	0/270 (0.00%)
Blood Alkaline Phosphatase Increased ^† 1	1/246 (0.41%)	0/270 (0.00%)
Blood Bilirubin Increased ^† 1	3/246 (1.22%)	0/270 (0.00%)
Haemoglobin Decreased ^† 1	1/246 (0.41%)	0/270 (0.00%)
Neutrophil Count Decreased ^† 1	1/246 (0.41%)	1/270 (0.37%)
Troponin I Increased ^† 1	1/246 (0.41%)	0/270 (0.00%)
Metabolism and nutrition disorders
Decreased Appetite ^† 1	2/246 (0.81%)	2/270 (0.74%)
Dehydration ^† 1	4/246 (1.63%)	4/270 (1.48%)
Diabetes Mellitus ^† 1	1/246 (0.41%)	1/270 (0.37%)
Diabetic Ketoacidosis ^† 1	0/246 (0.00%)	1/270 (0.37%)
Hyperglycaemia ^† 1	0/246 (0.00%)	2/270 (0.74%)
Hypoglycaemi ^† 1	1/246 (0.41%)	0/270 (0.00%)
Hypokalaemia ^† 1	1/246 (0.41%)	0/270 (0.00%)
Hyponatraemia ^† 1	2/246 (0.81%)	0/270 (0.00%)
Hypovolaemia ^† 1	1/246 (0.41%)	0/270 (0.00%)
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain ^† 1	0/246 (0.00%)	1/270 (0.37%)
Neck Pain ^† 1	1/246 (0.41%)	0/270 (0.00%)
Pain In Extremity ^† 1	1/246 (0.41%)	0/270 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer ^† 1	0/246 (0.00%)	1/270 (0.37%)
Colon Neoplasm ^† 1	0/246 (0.00%)	1/270 (0.37%)
Malignant Ascites ^† 1	1/246 (0.41%)	0/270 (0.00%)
Metastatic Pain ^† 1	0/246 (0.00%)	1/270 (0.37%)
Thyroid Cancer ^† 1	1/246 (0.41%)	0/270 (0.00%)
Nervous system disorders
Balance Disorder ^† 1	0/246 (0.00%)	1/270 (0.37%)
Cerebral Haemorrhage ^† 1	0/246 (0.00%)	1/270 (0.37%)
Cerebral Infarction ^† 1	1/246 (0.41%)	1/270 (0.37%)
Cerebrovascular Accident ^† 1	3/246 (1.22%)	1/270 (0.37%)
Dizziness ^† 1	1/246 (0.41%)	0/270 (0.00%)
Headache ^† 1	2/246 (0.81%)	0/270 (0.00%)
Hepatic Encephalopathy ^† 1	1/246 (0.41%)	0/270 (0.00%)
Ischaemic Stroke ^† 1	1/246 (0.41%)	0/270 (0.00%)
Loss Of Consciousness ^† 1	0/246 (0.00%)	1/270 (0.37%)
Presyncope ^† 1	1/246 (0.41%)	0/270 (0.00%)
Syncope ^† 1	1/246 (0.41%)	2/270 (0.74%)
Transient Ischaemic Attack ^† 1	0/246 (0.00%)	1/270 (0.37%)
Psychiatric disorders
Confusional State ^† 1	1/246 (0.41%)	4/270 (1.48%)
Hallucination ^† 1	0/246 (0.00%)	1/270 (0.37%)
Mental Status Changes ^† 1	1/246 (0.41%)	0/270 (0.00%)
Renal and urinary disorders
Oliguria ^† 1	1/246 (0.41%)	0/270 (0.00%)
Renal Failure Acute ^† 1	3/246 (1.22%)	1/270 (0.37%)
Renal Impairment ^† 1	1/246 (0.41%)	0/270 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome ^† 1	0/246 (0.00%)	1/270 (0.37%)
Chronic Obstructive Pulmonary Disease ^† 1	1/246 (0.41%)	0/270 (0.00%)
Dyspnea ^† 1	1/246 (0.41%)	0/270 (0.00%)
Dyspnoea ^† 1	2/246 (0.81%)	3/270 (1.11%)
Epistaxis ^† 1	2/246 (0.81%)	2/270 (0.74%)
Hiccups ^† 1	0/246 (0.00%)	1/270 (0.37%)
Laryngeal Dyspnoea ^† 1	0/246 (0.00%)	1/270 (0.37%)
Pneumonitis ^† 1	0/246 (0.00%)	2/270 (0.74%)
Pulmonary embolism ^† 1	11/246 (4.47%)	6/270 (2.22%)
Respiratory Failure ^† 1	2/246 (0.81%)	0/270 (0.00%)
Respiratory Tract Haemorrhage ^† 1	1/246 (0.41%)	0/270 (0.00%)
Skin and subcutaneous tissue disorders
Urticaria ^† 1	0/246 (0.00%)	1/270 (0.37%)
Social circumstances
Physical Assault ^† 1	1/246 (0.41%)	0/270 (0.00%)
Social Stay Hospitalisation ^† 1	1/246 (0.41%)	0/270 (0.00%)
Surgical and medical procedures
Abscess Drainage ^† 1	0/246 (0.00%)	1/270 (0.37%)
Gastrointestinal Surgery ^† 1	1/246 (0.41%)	0/270 (0.00%)
Hernia Repair ^† 1	1/246 (0.41%)	0/270 (0.00%)
Surgery NOS ^† 1 [1]	1/246 (0.41%)	0/270 (0.00%)
Vascular disorders
Artery Dissection ^† 1	1/246 (0.41%)	1/270 (0.37%)
Circulatory Collapse ^† 1	0/246 (0.00%)	1/270 (0.37%)
Deep Vein Thrombosis ^† 1	3/246 (1.22%)	2/270 (0.74%)
Embolism ^† 1	1/246 (0.41%)	0/270 (0.00%)
Femoral Artery Occlusion ^† 1	0/246 (0.00%)	1/270 (0.37%)
Haematoma ^† 1	2/246 (0.81%)	1/270 (0.37%)
Hypertension ^† 1	4/246 (1.63%)	0/270 (0.00%)
Hypotension ^† 1	3/246 (1.22%)	2/270 (0.74%)
Hypovolaemic Shock ^† 1	0/246 (0.00%)	1/270 (0.37%)
Ischaemia ^† 1	0/246 (0.00%)	1/270 (0.37%)
Orthostatic Hypotension ^† 1	0/246 (0.00%)	1/270 (0.37%)
Peripheral Artery Stenosis ^† 1	0/246 (0.00%)	1/270 (0.37%)
Peripheral Artery Thrombosis ^† 1	1/246 (0.41%)	0/270 (0.00%)
Peripheral Embolism ^† 1	0/246 (0.00%)	1/270 (0.37%)
Phlebitis ^† 1	1/246 (0.41%)	0/270 (0.00%)
Thrombosis ^† 1	0/246 (0.00%)	2/270 (0.74%)
Venous Thrombosis Limb ^† 1	1/246 (0.41%)	0/270 (0.00%)
1 Term from vocabulary, MedDRA (16.1) † Indicates events were collected by systematic assessment [1] NOS: Not Otherwise Specified
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	mFOLFOX6 Plus SIRT	mFOLFOX6 Alone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	112/246 (45.53%)	157/270 (58.15%)
Blood and lymphatic system disorders
Anaemia ^† 1	29/246 (11.79%)	38/270 (14.07%)
Febrile Neutropenia ^† 1	15/246 (6.10%)	5/270 (1.85%)
Leukopenia ^† 1	33/246 (13.41%)	21/270 (7.78%)
Lymphopenia ^† 1	15/246 (6.10%)	5/270 (1.85%)
Neutropenia ^† 1	66/246 (26.83%)	102/270 (37.78%)
Thrombocytopenia ^† 1	97/246 (39.43%)	47/270 (17.41%)
Gastrointestinal disorders
Abdominal Pain ^† 1	103/246 (41.87%)	53/270 (19.63%)
Abdominal Pain Upper ^† 1	77/246 (31.30%)	22/270 (8.15%)
Ascites ^† 1	23/246 (9.35%)	4/270 (1.48%)
Constipation ^† 1	108/246 (43.90%)	91/270 (33.70%)
Diarrhoea ^† 1	103/246 (41.87%)	132/270 (48.89%)
Dyspepsia ^† 1	25/246 (10.16%)	22/270 (8.15%)
Gastrooesophageal Reflux Disease ^† 1	18/246 (7.32%)	25/270 (9.26%)
Nausea ^† 1	15/246 (6.10%)	137/270 (50.74%)
Rectal Haemorrhage ^† 1	23/246 (9.35%)	18/270 (6.67%)
Stomatitis ^† 1	45/246 (18.29%)	47/270 (17.41%)
Vomiting ^† 1	95/246 (38.62%)	74/270 (27.41%)
General disorders
Asthenia ^† 1	39/246 (15.85%)	27/270 (10.00%)
Chest Pain ^† 1	23/246 (9.35%)	10/270 (3.70%)
Fatigue ^† 1	26/246 (10.57%)	134/270 (49.63%)
Mucosal Inflammation ^† 1	40/246 (16.26%)	54/270 (20.00%)
Oedema Peripheral ^† 1	35/246 (14.23%)	17/270 (6.30%)
Pyrexia ^† 1	57/246 (23.17%)	43/270 (15.93%)
Immune system disorders
Drug Hypersensitivity ^† 1	13/246 (5.28%)	7/270 (2.59%)
Infections and infestations
Upper Respiratory Tract Infection ^† 1	15/246 (6.10%)	24/270 (8.89%)
Urinary Tract Infection ^† 1	19/246 (7.72%)	15/270 (5.56%)
Injury, poisoning and procedural complications
Procedural Pain ^† 1	32/246 (13.01%)	4/270 (1.48%)
Blood Alkaline Phosphatase Increased ^† 1	13/246 (5.28%)	8/270 (2.96%)
Investigations
Aspartate Aminotransferase Increased ^† 1	13/246 (5.28%)	7/270 (2.59%)
Neutrophil Count Decreased ^† 1	25/246 (10.16%)	12/270 (4.44%)
Platelet Count Decreased ^† 1	25/246 (10.16%)	10/270 (3.70%)
Weight Decreased ^† 1	55/246 (22.36%)	39/270 (14.44%)
Weight Increased ^† 1	15/246 (6.10%)	21/270 (7.78%)
White Blood Cell Count Decreased ^† 1	15/246 (6.10%)	4/270 (1.48%)
Metabolism and nutrition disorders
Decreased Appetite ^† 1	77/246 (31.30%)	77/270 (28.52%)
Dehydration ^† 1	14/246 (5.69%)	12/270 (4.44%)
Hyperglycaemia ^† 1	10/246 (4.07%)	16/270 (5.93%)
Hypokalaemia ^† 1	23/246 (9.35%)	15/270 (5.56%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	16/246 (6.50%)	12/270 (4.44%)
Back Pain ^† 1	32/246 (13.01%)	22/270 (8.15%)
Musculoskeletal Pain ^† 1	21/246 (8.54%)	16/270 (5.93%)
Pain In Extremity ^† 1	16/246 (6.50%)	14/270 (5.19%)
Nervous system disorders
Dizziness ^† 1	25/246 (10.16%)	29/270 (10.74%)
Dysgeusia ^† 1	56/246 (22.76%)	52/270 (19.26%)
Headache ^† 1	35/246 (14.23%)	28/270 (10.37%)
Lethargy ^† 1	13/246 (5.28%)	13/270 (4.81%)
Neuropathy Peripheral ^† 1	12/246 (4.88%)	15/270 (5.56%)
Paraesthesia ^† 1	32/246 (13.01%)	47/270 (17.41%)
Peripheral Sensory Neuropathy ^† 1	41/246 (16.67%)	43/270 (15.93%)
Polyneuropathy ^† 1	13/246 (5.28%)	17/270 (6.30%)
Psychiatric disorders
Anxiety ^† 1	9/246 (3.66%)	15/270 (5.56%)
Depression ^† 1	15/246 (6.10%)	8/270 (2.96%)
Insomnia ^† 1	35/246 (14.23%)	36/270 (13.33%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	32/246 (13.01%)	34/270 (12.59%)
Dyspnoea ^† 1	23/246 (9.35%)	30/270 (11.11%)
Epistaxis ^† 1	61/246 (24.80%)	68/270 (25.19%)
Hiccups ^† 1	13/246 (5.28%)	15/270 (5.56%)
Oropharyngeal Pain ^† 1	14/246 (5.69%)	13/270 (4.81%)
Pulmonary Embolism ^† 1	18/246 (7.32%)	15/270 (5.56%)
Skin and subcutaneous tissue disorders
Alopecia ^† 1	29/246 (11.79%)	31/270 (11.48%)
Dry Skin ^† 1	20/246 (8.13%)	19/270 (7.04%)
Palmar-Plantar Erythrodysaesthesia ^† 1	21/246 (8.54%)	27/270 (10.00%)
Rash ^† 1	32/246 (13.01%)	35/270 (12.96%)
Vascular disorders
Hypertension ^† 1	42/246 (17.07%)	48/270 (17.78%)
Hypotension ^† 1	13/246 (5.28%)	14/270 (5.19%)
1 Term from vocabulary, MedDRA (16.1) † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Janet Bell, M.B.A.
Organization:	Sirtex Medical
Phone:	+ 888-474-7839 ext 710
EMail:	jbell@sirtex.com

Publications of Results:

van Hazel GA, Heinemann V, Sharma NK, Findlay MP, Ricke J, Peeters M, Perez D, Robinson BA, Strickland AH, Ferguson T, Rodriguez J, Kroning H, Wolf I, Ganju V, Walpole E, Boucher E, Tichler T, Shacham-Shmueli E, Powell A, Eliadis P, Isaacs R, Price D, Moeslein F, Taieb J, Bower G, Gebski V, Van Buskirk M, Cade DN, Thurston K, Gibbs P. SIRFLOX: Randomized Phase III Trial Comparing First-Line mFOLFOX6 (Plus or Minus Bevacizumab) Versus mFOLFOX6 (Plus or Minus Bevacizumab) Plus Selective Internal Radiation Therapy in Patients With Metastatic Colorectal Cancer. J Clin Oncol. 2016 May 20;34(15):1723-31. doi: 10.1200/JCO.2015.66.1181. Epub 2016 Feb 22. Erratum In: J Clin Oncol. 2016 Nov 20;34(33):4059.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wolstenholme J, Fusco F, Gray AM, Moschandreas J, Virdee PS, Love S, Van Hazel G, Gibbs P, Wasan HS, Sharma RA. Quality of life in the FOXFIRE, SIRFLOX and FOXFIRE-global randomised trials of selective internal radiotherapy for metastatic colorectal cancer. Int J Cancer. 2020 Aug 15;147(4):1078-1085. doi: 10.1002/ijc.32828. Epub 2020 Jan 9.

Wasan HS, Gibbs P, Sharma NK, Taieb J, Heinemann V, Ricke J, Peeters M, Findlay M, Weaver A, Mills J, Wilson C, Adams R, Francis A, Moschandreas J, Virdee PS, Dutton P, Love S, Gebski V, Gray A; FOXFIRE trial investigators; SIRFLOX trial investigators; FOXFIRE-Global trial investigators; van Hazel G, Sharma RA. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials. Lancet Oncol. 2017 Sep;18(9):1159-1171. doi: 10.1016/S1470-2045(17)30457-6. Epub 2017 Aug 3.

Virdee PS, Moschandreas J, Gebski V, Love SB, Francis EA, Wasan HS, van Hazel G, Gibbs P, Sharma RA. Protocol for Combined Analysis of FOXFIRE, SIRFLOX, and FOXFIRE-Global Randomized Phase III Trials of Chemotherapy +/- Selective Internal Radiation Therapy as First-Line Treatment for Patients With Metastatic Colorectal Cancer. JMIR Res Protoc. 2017 Mar 28;6(3):e43. doi: 10.2196/resprot.7201.

Gibbs P, Gebski V, Van Buskirk M, Thurston K, Cade DN, Van Hazel GA; SIRFLOX Study Group. Selective Internal Radiation Therapy (SIRT) with yttrium-90 resin microspheres plus standard systemic chemotherapy regimen of FOLFOX versus FOLFOX alone as first-line treatment of non-resectable liver metastases from colorectal cancer: the SIRFLOX study. BMC Cancer. 2014 Dec 1;14:897. doi: 10.1186/1471-2407-14-897.

Layout table for additonal information

Responsible Party:	Sirtex Medical
ClinicalTrials.gov Identifier:	NCT00724503
Other Study ID Numbers:	STX0206
First Submitted:	July 25, 2008
First Posted:	July 29, 2008
Results First Submitted:	November 7, 2018
Results First Posted:	March 26, 2019
Last Update Posted:	March 26, 2019

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