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

• Sponsor: Sirtex Medical (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00724503
• Collaborator: (none)
• Enrollment: 530
• Locations: 111
• Arms: 2
• Actual Duration (Months): 105
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study is a randomized multi-center trial that will assess the effect of adding Selective Internal Radiation Therapy (SIRT), using SIR-Spheres microspheres®, to a standard chemotherapy regimen of FOLFOX as first line therapy in patients with non-resectable liver metastases from primary colorectal adenocarcinoma.

Treatment with the biologic agent bevacizumab, if part of the standard of care at participating institutions, is allowed within this study at the discretion of the treating Investigator.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer; Colorectal Carcinoma; Liver Metastases	Device: SIR-Spheres yttrium-90 microspheres; Drug: Systemic chemotherapy (FOLFOX)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 530 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomised Comparative Study Of Folfox6m Plus Sir-Spheres® Microspheres Versus Folfox6m Alone As First Line Treatment In Patients With Nonresectable Liver Metastases From Primary Colorectal Carcinoma
• Actual Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mFOLFOX6 + SIRT A single injection of SIR-Spheres microspheres into the liver plus systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)	Device: SIR-Spheres yttrium-90 microspheres; SIR-Spheres microspheres (yttrium-90 [Y-90] labelled resin microspheres), hepatic artery injection administered on Day 3 or 4 of cycle 1. mFOLFOX6 administered on Day 1 and at the start of each cycle every 14 days: 85 or 60 mg/m2 oxaliplatin by 2-hour intravenous (IV) infusion + 200 mg/m2 leucovorin by 2-hour IV infusion + 400 mg/m2 5-fluorouracil (5-FU) by IV bolus + 2.4 g/m2 5-FU by 46-hour continuous IV infusion. Treatment with the biologic agent bevacizumab, if part of standard practice at the participating institution, was permitted at the discretion of the treating Investigator. In the event that leucovorin was not available, use of levofolinic acid (the active S enantiomer) was acceptable at half the dose of the racemic leucovorin i.e. 100 mg/m2.; Other Names: mFOLFOX6m + SIRT SIR-Spheres Y-90 microspheres
Active Comparator: mFOLFOX6 Systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5- Fluorouracil (FOLFOX).	Drug: Systemic chemotherapy (FOLFOX); mFOLFOX6 administered on Day 1 and at the start of each cycle every 14 days: 85 or 60 mg/m2 oxaliplatin by 2-hour intravenous (IV) infusion + 200 mg/m2 leucovorin by 2-hour IV infusion + 400 mg/m2 5-fluorouracil (5-FU) by IV bolus + 2.4 g/m2 5-FU by 46-hour continuous IV infusion. Treatment with the biologic agent bevacizumab, if part of standard practice at the participating institution, was permitted at the discretion of the treating Investigator. In the event that leucovorin was not available, use of levofolinic acid (the active S enantiomer) was acceptable at half the dose of the racemic leucovorin i.e. 100 mg/m2.; Other Names: mFOLFOX6

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) at Any Site [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]

   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.

Secondary Outcome Measures

1. Percentage of Participants With Overall Response [Through study completion, up to 60 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Unequivocal and measurable CT evidence of liver metastases which are not treatable by surgical resection or local ablation.

• Limited extra-hepatic metastases in the lung and/or lymph nodes are permitted (Lung: 5 lesions total, < 1 cm, or 1 single lesion of up to 1.7 cm; Lymph nodules in one single anatomic area (pelvis, abdomen or chest): any number, < 2 cm).

• Suitable for either treatment regimen.

• Prior chemotherapy for metastatic colorectal cancer is not allowed.

• WHO performance status 0-1.

• Adequate hematological, renal and hepatic function.

• Age 18 years or older.

• Willing and able to provide written informed consent.

• Life expectancy of at least 3 months without any active treatment.

Exclusion Criteria

• Evidence of ascites, cirrhosis, portal hypertension, main portal or venous tumor involvement or thrombosis as determined by clinical or radiologic assessment.

• Previous radiotherapy delivered to the upper abdomen.

• Non-malignant disease that would render the patient unsuitable for treatment according to the protocol.

• Peripheral neuropathy > grade 1 (NCI-CTC).

• Dose limiting toxicity with previous adjuvant 5-FU or oxaliplatin chemotherapy.

• Prior non-adjuvant chemotherapy for any malignancy. Adjuvant chemotherapy for colorectal cancer is not an exclusion criteria provided that it was completed more than 6 months before entry into the study.

• Pregnant or breast-feeding.

• Other active malignancy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Oncology Hematology	Scottsdale	Arizona	United States	85258
2	City of Hope Hospital	Duarte	California	United States	91010
3	Florida International University College of Medicine Practice	North Miami Beach	Florida	United States	33169
4	Vanguard Health	Berwyn	Illinois	United States	60402
5	University of Illinois at Chicago	Chicago	Illinois	United States	60612
6	Ingalls Memorial Hospital	Harvey	Illinois	United States	80426
7	Adventist Hinsdale Hospital	Hinsdale	Illinois	United States	60525
8	University of Louisville	Louisville	Kentucky	United States	40202
9	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
10	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
11	Virginia Piper Cancer Institute	Minneapolis	Minnesota	United States	55407
12	Holy Name Hospital	Teaneck	New Jersey	United States	07666
13	Montefiore Medical Center	Bronx	New York	United States	10467
14	Carolinas Hematology-Oncology Associates	Charlotte	North Carolina	United States	28203
15	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
16	Altru Health Systems	Grand Forks	North Dakota	United States	58201
17	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15232
18	St. Mark's Hospital	Salt Lake City	Utah	United States	84124
19	University of Washington	Seattle	Washington	United States	98109
20	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
21	Medical College of Wisconsin/Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin	United States	53226
22	Concord Hospital	Concord	New South Wales	Australia	2139
23	St. Vincent's Hospital	Darlinghurst	New South Wales	Australia	2010
24	Nepean Cancer Care Centre	Kingswood	New South Wales	Australia
25	St. George Hospital	Kogarah	New South Wales	Australia	2217
26	Royal North Shore Hospital	St Leonards	New South Wales	Australia	2065
27	Sydney Adventist Hospital	Wahroonga	New South Wales	Australia	2076
28	Westmead Hospital	Westmead	New South Wales	Australia	2145
29	Wesley Medical Centre	Auchenflower	Queensland	Australia	4066
30	Cairns Private Hospital	Cairns	Queensland	Australia	4870
31	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
32	Gold Coast Health Service District	Southport	Queensland	Australia	4215
33	HOCA Gold Coast Centre	Southport	Queensland	Australia	4215
34	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia
35	Royal Adelaide Hospital	Adelaide	South Australia	Australia
36	Ashford Cancer Centre	Ashford	South Australia	Australia
37	Flinders Medical Centre	Bedford Park	South Australia	Australia
38	Lyell McEwin Hospital	Elizabeth Vale	South Australia	Australia	5012
39	Queen Elizabeth II Hospital	Woodville South	South Australia	Australia
40	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
41	Monash Medical Centre	Bentleigh East	Victoria	Australia
42	John Fawkner Private Hospital	Coburg	Victoria	Australia	3058
43	Western Hospital	Footscray	Victoria	Australia	3011
44	Peninsula Oncology Centre	Frankston	Victoria	Australia	3199
45	South Eastern Private	Noble Park	Victoria	Australia	3174
46	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
47	Maroondah Public	Ringwood East	Victoria	Australia	3135
48	Ringwood/Knox Private	Ringwood	Victoria	Australia	3135
49	Hollywood Private Hospital	Nedlands	Western Australia	Australia	6009
50	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia
51	Mount Medical Centre	Perth	Western Australia	Australia	6005
52	Royal Perth Hospital	Perth	Western Australia	Australia
53	OL Vrouw Ziekenhuis Aalst Gastro-Enterologie	Aalst		Belgium	9300
54	ZNA Middelheim	Antwerpen		Belgium	2020
55	Antwerp University Hospital	Antwerp		Belgium
56	Imelda Ziekenhuis GI Clinical Research Centre	Bonheiden		Belgium	2820
57	Sint-Josef Ziekenhuie (Campus Bornem)	Bornem		Belgium	2880
58	Institut Jules Bordet - Centre de Tumeurs d'ULB	Brussels		Belgium
59	Universiteits Ziekenhuis Gent	Gent		Belgium	9000
60	AZ Maria Middelares	Gent		Belgium
61	Hospital de Jolimont	Haine-Saint-Paul		Belgium	7100
62	UZ Leuven, Campus Gasthuisberg	Leuven		Belgium	3000
63	Centre Hospitalier Universitaire de Liege	Liege		Belgium
64	VZW Emmaus St. Maarten Ziekenhuis Mechelen and St. Marten Ziekenhuis Duffel	Mechelen		Belgium	2800
65	AZ Heilige Familie	Reet		Belgium	2840
66	Sint-Augustinus Ziekenhuis	Wilrijk		Belgium	2610
67	CHU de Bordeau	Bordeaux		France	33000
68	Hospitalier Universitaire de Grenoble C.H.U.	La Tronche		France	38700
69	Centre Hospitalier General de Longjumeau	Longjumeau		France	91161
70	Hopital de l'Archet II, CHU de Nice	Nice		France	06202
71	Hospital European Georges Pompidou	Paris		France	7590
72	Centre Eugene Marquis	Rennes Cedex		France
73	Internistische Gemeinschaftspraxis	Altstadt		Germany	84028
74	Charite Campus Virchow Klinikum	Berlin		Germany	1335
75	Braxiskooperation Bonn, Fachartze fur Innere Medizin	Bonn		Germany	53123
76	Johanniterkrankenhaus Bonn	Bonn		Germany
77	Universitaetsklinikum Bonn	Bonn		Germany
78	Kliniken Essen Mitte	Essen		Germany	45136
79	Gemeinschaftspraxis Hamatologie und internistische Onkologie	Essen		Germany
80	Universitat Frankfurt Institute fur Diagnostic und Interventionelle Radiologie	Frankfurt		Germany	6059
81	Asklepios Klinik Altona, Abt. Radiologie, Neuroradiologie, Nuklearmedizin	Hamburg		Germany	20367
82	Universitastsklinikum Saarland	Hamburg		Germany
83	Praxisgemeinschaft Dr. med. Peter Sandor und Peter Kohl	Holzkirch		Germany	83607
84	Onklogische Praxis Dr. Gerald Gehbauer	Ingolstadt		Germany	85049
85	Klinikum Karlsruhe, Stadtisches Klinikum Karlsruhe, Zentralinstitut fur Bildgebende Diagnostik	Karlsruhe		Germany	76133
86	Schwerpunktpraxis fur Hamatologie und Onkologie	Magdeburg		Germany	39104
87	Klinikum Magdeburg GmbH, Klinik für Hämatologie/Onkologie	Magdeburg		Germany	39130
88	Universitaetsklinikum Magdeburg	Magdeburg		Germany
89	Universitatsklinikum GieBen und Marburg	Marburg		Germany	35043
90	Klinikum Bogenhausen	Muenchen		Germany
91	Klinikum der Universitaet Muenchen	Muenchen		Germany
92	Hamato-Onkologische Schwerpunktspraxis	Munchen		Germany
93	Klinikum rechts der Isar der TU Munchen	Munchen		Germany
94	Schwerpunktspraxis fur Hamatologie und Internistische Onkologie	Munchen		Germany
95	Praxis fur Hamatologie und Internnistische Onkologie	Velbert		Germany	42551
96	Schwerpunktspraxis und Tagesklinik Dr. Perker/Dr. Sandherr	Weilheim		Germany
97	Rambam Medical Center	Haifa		Israel
98	Shaare-Zedek Medical Centre	Jerusalem		Israel	91031
99	Rabin Medical Center, Beilinson Hospital	Petah Tiqva		Israel	49100
100	Sheba Medical Center	Ramat Gan		Israel	52621
101	TA Sourasky Medical Center	Tel Aviv		Israel	64239
102	A.O.U. die Bologna	Bologna		Italy	40138
103	University of Auckland	Auckland		New Zealand
104	Christchurch Hospital	Christchurch		New Zealand
105	Dunedin Hospital	Dunedin		New Zealand
106	Wellington Hospital	Newtown		New Zealand
107	Palmerston North Hospital	Palmerston		New Zealand
108	Wojskowy Instytut Medyczny (WIM)	Warsaw		Poland	04-141
109	Clinica Universitaria de Navarra	Pamplona		Spain	31008
110	Hospital de Navarra, Servicio de Ongoligia, Planta Baja	Pamplona		Spain	31008
111	Universitatsspital Zurich	Zurich		Switzerland	CH-8091

Sponsors and Collaborators

• Sirtex Medical

Investigators

• Principal Investigator: Peter Gibbs, MD, Melbourne Health
• Principal Investigator: Guy van Hazel, MD, Mount Medical Centre

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sirtex Medical
• ClinicalTrials.gov Identifier: NCT00724503
• Other Study ID Numbers: STX0206
• First Posted: Jul 29, 2008
• Last Update Posted: Mar 26, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Sirtex Medical: colon cancer; Colorectal carcinoma; liver metastases; SIR-Spheres microspheres; yttrium-90; FOLFOX; bevacizumab; metastatic colorectal cancer
• Additional relevant MeSH terms: Carcinoma; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms

Study Results

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.

Arm/Group Title	mFOLFOX6 Plus SIRT	mFOLFOX6 Alone
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

Baseline Characteristics

Arm/Group Title	mFOLFOX6 Plus SIRT	mFOLFOX6 Alone	Total
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 Participants	267	263	530
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63	63	63
Sex: Female, Male (Count of Participants)
Female	85 31.8%	88 33.5%	173 32.6%
Male	182 68.2%	174 66.2%	356 67.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	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%
Black or African American	2 0.7%	8 3%	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 (participants) [Number]
0	176 65.9%	175 66.5%	351 66.2%
1	90 33.7%	87 33.1%	177 33.4%
Unknown	1 0.4%	1 0.4%	2 0.4%
Primary tumor in situ (Count of Participants)
No	148 55.4%	141 53.6%	289 54.5%
Yes	119 44.6%	121 46%	240 45.3%
Unknown	0 0%	1 0.4%	1 0.2%
Extra-hepatic metastases at randomization (participants) [Number]
No	160 59.9%	159 60.5%	319 60.2%
Yes	107 40.1%	104 39.5%	211 39.8%
Tumor liver involvement % (Count of Participants)
<=25%	185 69.3%	192 73%	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 (Count of Participants)
Count of Participants [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 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 microspheres into the liver plus systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)	Systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)
Measure Participants	267	263
Median (95% Confidence Interval) [Months]	10.7	10.2

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
Statistical Test of Hypothesis	p-Value	0.551
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Overall Response
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 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
Measure Participants	267	263
Number [percentage of participants]	76.4 28.6%	68.1 25.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	mFOLFOX6 Plus SIRT, mFOLFOX6 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
Statistical Test of Hypothesis	p-Value	< 0.05
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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 (%)	# Events	Affected / at Risk (%)	# Events
Total	190/246 (77.2%)		182/270 (67.4%)
Serious Adverse Events
	mFOLFOX6 Plus SIRT		mFOLFOX6 Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	134/246 (54.5%)		112/270 (41.5%)
Blood and lymphatic system disorders
Anaemia	1/246 (0.4%)		4/270 (1.5%)
Febrile Neutropenia	13/246 (5.3%)		4/270 (1.5%)
Heparin-Induced Thrombocytopenia	0/246 (0%)		1/270 (0.4%)
Neutropenia	3/246 (1.2%)		2/270 (0.7%)
Splenic Infarction	0/246 (0%)		1/270 (0.4%)
Thrombocytopenia	1/246 (0.4%)		1/270 (0.4%)
Cardiac disorders
Acute Coronary Syndrome	1/246 (0.4%)		0/270 (0%)
Acute Myocardial Infarction	2/246 (0.8%)		2/270 (0.7%)
Angina Pectoris	1/246 (0.4%)		1/270 (0.4%)
Arrhythmia	0/246 (0%)		1/270 (0.4%)
Arteriospasm Coronary	1/246 (0.4%)		0/270 (0%)
Atrial Fibrillation	1/246 (0.4%)		0/270 (0%)
Atrial Flutter	1/246 (0.4%)		0/270 (0%)
Atrioventricular Block Complete	0/246 (0%)		1/270 (0.4%)
Cardiac Arrest	0/246 (0%)		1/270 (0.4%)
Cardiac Failure	1/246 (0.4%)		1/270 (0.4%)
Intracardiac Thrombus	1/246 (0.4%)		0/270 (0%)
Myocardial Infarction	1/246 (0.4%)		0/270 (0%)
Stress Cardiomyopathy	0/246 (0%)		1/270 (0.4%)
Supraventricular Tachycardia	0/246 (0%)		1/270 (0.4%)
Congenital, familial and genetic disorders
Hydrocele	1/246 (0.4%)		0/270 (0%)
Ear and labyrinth disorders
Vertigo	0/246 (0%)		1/270 (0.4%)
Gastrointestinal disorders
Abdominal Pain	11/246 (4.5%)		5/270 (1.9%)
Abdominal Pain Upper	4/246 (1.6%)		1/270 (0.4%)
Anal Fissure	0/246 (0%)		2/270 (0.7%)
Anal Inflammation	0/246 (0%)		1/270 (0.4%)
Ascites	4/246 (1.6%)		0/270 (0%)
Constipation	10/246 (4.1%)		7/270 (2.6%)
Diarrhoea	11/246 (4.5%)		8/270 (3%)
Duodenal Ulcer	3/246 (1.2%)		1/270 (0.4%)
Duodenal Ulcer Haemorrhage	0/246 (0%)		1/270 (0.4%)
Duodenitis	2/246 (0.8%)		0/270 (0%)
Erosive Oesophagitis	1/246 (0.4%)		0/270 (0%)
Gastric Haemorrhage	1/246 (0.4%)		0/270 (0%)
Gastric Ulcer	6/246 (2.4%)		0/270 (0%)
Gastritis	4/246 (1.6%)		0/270 (0%)
Gastritis Atrophic	1/246 (0.4%)		0/270 (0%)
Gastritis Erosive	0/246 (0%)		1/270 (0.4%)
Gastroduodenitis	1/246 (0.4%)		0/270 (0%)
Gastrointestinal Haemorrhage	5/246 (2%)		1/270 (0.4%)
Haematemesis	2/246 (0.8%)		0/270 (0%)
Haemorrhoidal Haemorrhage	0/246 (0%)		1/270 (0.4%)
Haemorrhoids	0/246 (0%)		1/270 (0.4%)
Ileus	0/246 (0%)		1/270 (0.4%)
Intestinal Haematoma	0/246 (0%)		1/270 (0.4%)
Intestinal Obstruction	4/246 (1.6%)		6/270 (2.2%)
Intestinal Perforation	2/246 (0.8%)		3/270 (1.1%)
Large Intestinal Obstruction	2/246 (0.8%)		2/270 (0.7%)
Large Intestinal Stenosis	1/246 (0.4%)		0/270 (0%)
Large Intestine Perforation	1/246 (0.4%)		1/270 (0.4%)
Melaena	1/246 (0.4%)		1/270 (0.4%)
Nausea	8/246 (3.3%)		4/270 (1.5%)
Oesophageal Ulcer	1/246 (0.4%)		0/270 (0%)
Oesophageal Varices Haemorrhage	1/246 (0.4%)		1/270 (0.4%)
Oesophagitis	1/246 (0.4%)		0/270 (0%)
Oesophagitis Haemorrhagic	0/246 (0%)		1/270 (0.4%)
Oral Pain	0/246 (0%)		1/270 (0.4%)
Pancreatitis	3/246 (1.2%)		0/270 (0%)
Proctalgia	1/246 (0.4%)		1/270 (0.4%)
Rectal Haemorrhage	3/246 (1.2%)		2/270 (0.7%)
Rectal Stenosis	0/246 (0%)		1/270 (0.4%)
Small Intestinal Obstruction	1/246 (0.4%)		0/270 (0%)
Stomatitis	3/246 (1.2%)		0/270 (0%)
Volvulus Of Small Bowel	0/246 (0%)		1/270 (0.4%)
Vomiting	16/246 (6.5%)		3/270 (1.1%)
General disorders
Asthenia	3/246 (1.2%)		1/270 (0.4%)
Chest Pain	3/246 (1.2%)		0/270 (0%)
Chills	1/246 (0.4%)		0/270 (0%)
Device Dislocation	0/246 (0%)		1/270 (0.4%)
Device Occlusion	0/246 (0%)		2/270 (0.7%)
Extravasation	0/246 (0%)		1/270 (0.4%)
Fatigue	4/246 (1.6%)		0/270 (0%)
General Physical Health Deterioration	1/246 (0.4%)		2/270 (0.7%)
Hernia	1/246 (0.4%)		0/270 (0%)
Influenza Like Illness	1/246 (0.4%)		0/270 (0%)
Infusion Site Pain	0/246 (0%)		1/270 (0.4%)
Malaise	1/246 (0.4%)		0/270 (0%)
Oedema Peripheral	1/246 (0.4%)		0/270 (0%)
Pain	1/246 (0.4%)		0/270 (0%)
Pyrexia	17/246 (6.9%)		12/270 (4.4%)
Hepatobiliary disorders
Bile Duct Obstruction	0/246 (0%)		1/270 (0.4%)
Bile Duct Stone	0/246 (0%)		1/270 (0.4%)
Cholangitis	2/246 (0.8%)		1/270 (0.4%)
Cholecystitis	1/246 (0.4%)		2/270 (0.7%)
Cholecystitis Acute	1/246 (0.4%)		0/270 (0%)
Cholelithiasis	0/246 (0%)		1/270 (0.4%)
Gallbladder Perforation	1/246 (0.4%)		0/270 (0%)
Hepatic Failure	3/246 (1.2%)		0/270 (0%)
Hepatic Fibrosis	1/246 (0.4%)		0/270 (0%)
Hepatic Infarction	1/246 (0.4%)		0/270 (0%)
Hepatic Pain	0/246 (0%)		1/270 (0.4%)
Hyperbilirubinaemia	1/246 (0.4%)		1/270 (0.4%)
Jaundice	1/246 (0.4%)		1/270 (0.4%)
Jaundice Cholestatic	2/246 (0.8%)		1/270 (0.4%)
Immune system disorders
Drug Hypersensitivity	1/246 (0.4%)		1/270 (0.4%)
Infections and infestations
Abdominal Wall Infection	1/246 (0.4%)		0/270 (0%)
Abscess Limb	1/246 (0.4%)		1/270 (0.4%)
Acute Sinusitis	0/246 (0%)		1/270 (0.4%)
Anorectal Infection	1/246 (0.4%)		0/270 (0%)
Campylobacter Gastroenteritis	0/246 (0%)		1/270 (0.4%)
Catheter Site Infection	0/246 (0%)		1/270 (0.4%)
Device Related Infection	2/246 (0.8%)		0/270 (0%)
Diverticulitis	0/246 (0%)		1/270 (0.4%)
Escherichia Bacteraemia	1/246 (0.4%)		0/270 (0%)
Gastroenteritis	5/246 (2%)		0/270 (0%)
Gastroenteritis Salmonella	1/246 (0.4%)		0/270 (0%)
Infection	2/246 (0.8%)		1/270 (0.4%)
Influenza	0/246 (0%)		1/270 (0.4%)
Infusion Site Infection	1/246 (0.4%)		2/270 (0.7%)
Klebsiella Sepsis	0/246 (0%)		1/270 (0.4%)
Liver Abscess	2/246 (0.8%)		0/270 (0%)
Lobar Pneumonia	1/246 (0.4%)		0/270 (0%)
Lower Respiratory Tract Infection	1/246 (0.4%)		0/270 (0%)
Lung Infection	1/246 (0.4%)		0/270 (0%)
Neutropenic Infection	2/246 (0.8%)		2/270 (0.7%)
Neutropenic Sepsis	1/246 (0.4%)		1/270 (0.4%)
Oesophageal Candidiasis	1/246 (0.4%)		0/270 (0%)
Pelvic Abscess	0/246 (0%)		1/270 (0.4%)
Perihepatic Abscess	2/246 (0.8%)		0/270 (0%)
Peritonitis	3/246 (1.2%)		0/270 (0%)
Pneumonia	3/246 (1.2%)		4/270 (1.5%)
Salmonellosis	0/246 (0%)		1/270 (0.4%)
Sepsis	1/246 (0.4%)		3/270 (1.1%)
Subcutaneous Abscess	1/246 (0.4%)		0/270 (0%)
Upper Respiratory Tract Infection	1/246 (0.4%)		2/270 (0.7%)
Urinary Tract Infection	0/246 (0%)		1/270 (0.4%)
Wound Infection	1/246 (0.4%)		0/270 (0%)
Injury, poisoning and procedural complications
Anastomotic Complication	0/246 (0%)		1/270 (0.4%)
Anastomotic Leak	0/246 (0%)		1/270 (0.4%)
Contrast Media Reaction	0/246 (0%)		1/270 (0.4%)
Fall	1/246 (0.4%)		2/270 (0.7%)
Femoral Neck Fracture	1/246 (0.4%)		0/270 (0%)
Gastroenteritis Radiation	1/246 (0.4%)		1/270 (0.4%)
Hip Fracture	1/246 (0.4%)		0/270 (0%)
Pelvic Fracture	1/246 (0.4%)		0/270 (0%)
Post Embolisation Syndrome	2/246 (0.8%)		0/270 (0%)
Post Procedural Bile Leak	2/246 (0.8%)		0/270 (0%)
Post Procedural Complication	0/246 (0%)		1/270 (0.4%)
Post Procedural Diarrhoea	0/246 (0%)		1/270 (0.4%)
Procedural Complication	1/246 (0.4%)		0/270 (0%)
Procedural Pain	2/246 (0.8%)		0/270 (0%)
Radiation Hepatitis	2/246 (0.8%)		0/270 (0%)
Rib Fracture	0/246 (0%)		1/270 (0.4%)
Spinal Fracture	0/246 (0%)		1/270 (0.4%)
Subdural Haematoma	0/246 (0%)		1/270 (0.4%)
Toxicity To Various Agents	0/246 (0%)		1/270 (0.4%)
Vascular Procedure Complication	1/246 (0.4%)		0/270 (0%)
Wound Evisceration	0/246 (0%)		1/270 (0.4%)
Investigations
Alanine Aminotransferase Increased	1/246 (0.4%)		0/270 (0%)
Aspartate Aminotransferase Increased	1/246 (0.4%)		0/270 (0%)
Blood Albumin Decreased	1/246 (0.4%)		0/270 (0%)
Blood Alkaline Phosphatase Increased	1/246 (0.4%)		0/270 (0%)
Blood Bilirubin Increased	3/246 (1.2%)		0/270 (0%)
Haemoglobin Decreased	1/246 (0.4%)		0/270 (0%)
Neutrophil Count Decreased	1/246 (0.4%)		1/270 (0.4%)
Troponin I Increased	1/246 (0.4%)		0/270 (0%)
Metabolism and nutrition disorders
Decreased Appetite	2/246 (0.8%)		2/270 (0.7%)
Dehydration	4/246 (1.6%)		4/270 (1.5%)
Diabetes Mellitus	1/246 (0.4%)		1/270 (0.4%)
Diabetic Ketoacidosis	0/246 (0%)		1/270 (0.4%)
Hyperglycaemia	0/246 (0%)		2/270 (0.7%)
Hypoglycaemi	1/246 (0.4%)		0/270 (0%)
Hypokalaemia	1/246 (0.4%)		0/270 (0%)
Hyponatraemia	2/246 (0.8%)		0/270 (0%)
Hypovolaemia	1/246 (0.4%)		0/270 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain	0/246 (0%)		1/270 (0.4%)
Neck Pain	1/246 (0.4%)		0/270 (0%)
Pain In Extremity	1/246 (0.4%)		0/270 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	0/246 (0%)		1/270 (0.4%)
Colon Neoplasm	0/246 (0%)		1/270 (0.4%)
Malignant Ascites	1/246 (0.4%)		0/270 (0%)
Metastatic Pain	0/246 (0%)		1/270 (0.4%)
Thyroid Cancer	1/246 (0.4%)		0/270 (0%)
Nervous system disorders
Balance Disorder	0/246 (0%)		1/270 (0.4%)
Cerebral Haemorrhage	0/246 (0%)		1/270 (0.4%)
Cerebral Infarction	1/246 (0.4%)		1/270 (0.4%)
Cerebrovascular Accident	3/246 (1.2%)		1/270 (0.4%)
Dizziness	1/246 (0.4%)		0/270 (0%)
Headache	2/246 (0.8%)		0/270 (0%)
Hepatic Encephalopathy	1/246 (0.4%)		0/270 (0%)
Ischaemic Stroke	1/246 (0.4%)		0/270 (0%)
Loss Of Consciousness	0/246 (0%)		1/270 (0.4%)
Presyncope	1/246 (0.4%)		0/270 (0%)
Syncope	1/246 (0.4%)		2/270 (0.7%)
Transient Ischaemic Attack	0/246 (0%)		1/270 (0.4%)
Psychiatric disorders
Confusional State	1/246 (0.4%)		4/270 (1.5%)
Hallucination	0/246 (0%)		1/270 (0.4%)
Mental Status Changes	1/246 (0.4%)		0/270 (0%)
Renal and urinary disorders
Oliguria	1/246 (0.4%)		0/270 (0%)
Renal Failure Acute	3/246 (1.2%)		1/270 (0.4%)
Renal Impairment	1/246 (0.4%)		0/270 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	0/246 (0%)		1/270 (0.4%)
Chronic Obstructive Pulmonary Disease	1/246 (0.4%)		0/270 (0%)
Dyspnea	1/246 (0.4%)		0/270 (0%)
Dyspnoea	2/246 (0.8%)		3/270 (1.1%)
Epistaxis	2/246 (0.8%)		2/270 (0.7%)
Hiccups	0/246 (0%)		1/270 (0.4%)
Laryngeal Dyspnoea	0/246 (0%)		1/270 (0.4%)
Pneumonitis	0/246 (0%)		2/270 (0.7%)
Pulmonary embolism	11/246 (4.5%)		6/270 (2.2%)
Respiratory Failure	2/246 (0.8%)		0/270 (0%)
Respiratory Tract Haemorrhage	1/246 (0.4%)		0/270 (0%)
Skin and subcutaneous tissue disorders
Urticaria	0/246 (0%)		1/270 (0.4%)
Social circumstances
Physical Assault	1/246 (0.4%)		0/270 (0%)
Social Stay Hospitalisation	1/246 (0.4%)		0/270 (0%)
Surgical and medical procedures
Abscess Drainage	0/246 (0%)		1/270 (0.4%)
Gastrointestinal Surgery	1/246 (0.4%)		0/270 (0%)
Hernia Repair	1/246 (0.4%)		0/270 (0%)
Surgery NOS	1/246 (0.4%)		0/270 (0%)
Vascular disorders
Artery Dissection	1/246 (0.4%)		1/270 (0.4%)
Circulatory Collapse	0/246 (0%)		1/270 (0.4%)
Deep Vein Thrombosis	3/246 (1.2%)		2/270 (0.7%)
Embolism	1/246 (0.4%)		0/270 (0%)
Femoral Artery Occlusion	0/246 (0%)		1/270 (0.4%)
Haematoma	2/246 (0.8%)		1/270 (0.4%)
Hypertension	4/246 (1.6%)		0/270 (0%)
Hypotension	3/246 (1.2%)		2/270 (0.7%)
Hypovolaemic Shock	0/246 (0%)		1/270 (0.4%)
Ischaemia	0/246 (0%)		1/270 (0.4%)
Orthostatic Hypotension	0/246 (0%)		1/270 (0.4%)
Peripheral Artery Stenosis	0/246 (0%)		1/270 (0.4%)
Peripheral Artery Thrombosis	1/246 (0.4%)		0/270 (0%)
Peripheral Embolism	0/246 (0%)		1/270 (0.4%)
Phlebitis	1/246 (0.4%)		0/270 (0%)
Thrombosis	0/246 (0%)		2/270 (0.7%)
Venous Thrombosis Limb	1/246 (0.4%)		0/270 (0%)
Other (Not Including Serious) Adverse Events
	mFOLFOX6 Plus SIRT		mFOLFOX6 Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	112/246 (45.5%)		157/270 (58.1%)
Blood and lymphatic system disorders
Anaemia	29/246 (11.8%)		38/270 (14.1%)
Febrile Neutropenia	15/246 (6.1%)		5/270 (1.9%)
Leukopenia	33/246 (13.4%)		21/270 (7.8%)
Lymphopenia	15/246 (6.1%)		5/270 (1.9%)
Neutropenia	66/246 (26.8%)		102/270 (37.8%)
Thrombocytopenia	97/246 (39.4%)		47/270 (17.4%)
Gastrointestinal disorders
Abdominal Pain	103/246 (41.9%)		53/270 (19.6%)
Abdominal Pain Upper	77/246 (31.3%)		22/270 (8.1%)
Ascites	23/246 (9.3%)		4/270 (1.5%)
Constipation	108/246 (43.9%)		91/270 (33.7%)
Diarrhoea	103/246 (41.9%)		132/270 (48.9%)
Dyspepsia	25/246 (10.2%)		22/270 (8.1%)
Gastrooesophageal Reflux Disease	18/246 (7.3%)		25/270 (9.3%)
Nausea	15/246 (6.1%)		137/270 (50.7%)
Rectal Haemorrhage	23/246 (9.3%)		18/270 (6.7%)
Stomatitis	45/246 (18.3%)		47/270 (17.4%)
Vomiting	95/246 (38.6%)		74/270 (27.4%)
General disorders
Asthenia	39/246 (15.9%)		27/270 (10%)
Chest Pain	23/246 (9.3%)		10/270 (3.7%)
Fatigue	26/246 (10.6%)		134/270 (49.6%)
Mucosal Inflammation	40/246 (16.3%)		54/270 (20%)
Oedema Peripheral	35/246 (14.2%)		17/270 (6.3%)
Pyrexia	57/246 (23.2%)		43/270 (15.9%)
Immune system disorders
Drug Hypersensitivity	13/246 (5.3%)		7/270 (2.6%)
Infections and infestations
Upper Respiratory Tract Infection	15/246 (6.1%)		24/270 (8.9%)
Urinary Tract Infection	19/246 (7.7%)		15/270 (5.6%)
Injury, poisoning and procedural complications
Procedural Pain	32/246 (13%)		4/270 (1.5%)
Blood Alkaline Phosphatase Increased	13/246 (5.3%)		8/270 (3%)
Investigations
Aspartate Aminotransferase Increased	13/246 (5.3%)		7/270 (2.6%)
Neutrophil Count Decreased	25/246 (10.2%)		12/270 (4.4%)
Platelet Count Decreased	25/246 (10.2%)		10/270 (3.7%)
Weight Decreased	55/246 (22.4%)		39/270 (14.4%)
Weight Increased	15/246 (6.1%)		21/270 (7.8%)
White Blood Cell Count Decreased	15/246 (6.1%)		4/270 (1.5%)
Metabolism and nutrition disorders
Decreased Appetite	77/246 (31.3%)		77/270 (28.5%)
Dehydration	14/246 (5.7%)		12/270 (4.4%)
Hyperglycaemia	10/246 (4.1%)		16/270 (5.9%)
Hypokalaemia	23/246 (9.3%)		15/270 (5.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	16/246 (6.5%)		12/270 (4.4%)
Back Pain	32/246 (13%)		22/270 (8.1%)
Musculoskeletal Pain	21/246 (8.5%)		16/270 (5.9%)
Pain In Extremity	16/246 (6.5%)		14/270 (5.2%)
Nervous system disorders
Dizziness	25/246 (10.2%)		29/270 (10.7%)
Dysgeusia	56/246 (22.8%)		52/270 (19.3%)
Headache	35/246 (14.2%)		28/270 (10.4%)
Lethargy	13/246 (5.3%)		13/270 (4.8%)
Neuropathy Peripheral	12/246 (4.9%)		15/270 (5.6%)
Paraesthesia	32/246 (13%)		47/270 (17.4%)
Peripheral Sensory Neuropathy	41/246 (16.7%)		43/270 (15.9%)
Polyneuropathy	13/246 (5.3%)		17/270 (6.3%)
Psychiatric disorders
Anxiety	9/246 (3.7%)		15/270 (5.6%)
Depression	15/246 (6.1%)		8/270 (3%)
Insomnia	35/246 (14.2%)		36/270 (13.3%)
Respiratory, thoracic and mediastinal disorders
Cough	32/246 (13%)		34/270 (12.6%)
Dyspnoea	23/246 (9.3%)		30/270 (11.1%)
Epistaxis	61/246 (24.8%)		68/270 (25.2%)
Hiccups	13/246 (5.3%)		15/270 (5.6%)
Oropharyngeal Pain	14/246 (5.7%)		13/270 (4.8%)
Pulmonary Embolism	18/246 (7.3%)		15/270 (5.6%)
Skin and subcutaneous tissue disorders
Alopecia	29/246 (11.8%)		31/270 (11.5%)
Dry Skin	20/246 (8.1%)		19/270 (7%)
Palmar-Plantar Erythrodysaesthesia	21/246 (8.5%)		27/270 (10%)
Rash	32/246 (13%)		35/270 (13%)
Vascular disorders
Hypertension	42/246 (17.1%)		48/270 (17.8%)
Hypotension	13/246 (5.3%)		14/270 (5.2%)

Limitations/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.