FOXFIREGlobal: FOLFOX6m Plus SIR-Spheres Microspheres vs FOLFOX6m Alone in Patients With Liver Mets From Primary Colorectal Cancer

• Sponsor: Sirtex Medical (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01721954
• Collaborator: (none)
• Enrollment: 209
• Locations: 83
• Arms: 2
• Actual Duration (Months): 46
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is a randomized, multi-center study that will compare the efficacy and safety of selective internal radiation therapy (SIRT) using SIR-Spheres microspheres plus a standard chemotherapy regimen of FOLFOX6m versus FOLFOX6m alone as first-line therapy in patients with non-resectable liver metastases from primary colorectal carcinoma.

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 Investigator.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Metastatic	Drug: FOLFOX6m; Device: SIR-Spheres microspheres	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 209 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessment of Overall Survival of FOLFOX6m Plus SIR-Spheres Microspheres Versus FOLFOX6m Alone as First-line Treatment in Patients With Non-resectable Liver Metastases From Primary Colorectal Carcinoma in a Randomised Clinical Study
• Actual Study Start Date: May 1, 2013
• Actual Primary Completion Date: Dec 23, 2016
• Actual Study Completion Date: Feb 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control Arm Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab repeated every two weeks until evidence of treatment failure.	Drug: FOLFOX6m
Experimental: Experimental Arm Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab plus SIR-Spheres microspheres.	Drug: FOLFOX6m; Device: SIR-Spheres microspheres

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [From date of randomization until the date of death from any cause assessed up 3 yrs 8 months]

   OS defined as the time interval between the date of randomization and the date of death from any cause.

Secondary Outcome Measures

1. Progression-free Survival [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years 8 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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age 18 years or older

• Willing and able to provide written informed consent

• 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)

• All imaging evidence used as part of the screening process must be within 28 days

• Suitable for either treatment regimen

• WHO performance status 0-1

• Adequate hematological, renal and hepatic function

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

Exclusion Criteria:

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

• Previous radiotherapy delivered to the liver

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

• Peripheral neuropathy > grade 2 (NCI-CTC)

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

• Prior non-adjuvant chemotherapy for any malignancy. Adjuvant chemotherapy for colorectal cancer is permitted provided that it was completed more than 6 months before entry into the study

• Pregnant or breast feeding

• Concurrent or prior history of cancer other than adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix

• Allergy to contrast media that would preclude angiography of the hepatic arteries

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Orlando Health	Orlando	Florida	United States	32806
3	Memorial Healthcare	Pembroke Pines	Florida	United States	33028
4	University of Illinois Chicago	Chicago	Illinois	United States	60607
5	Adventist Midwest Health	Hinsdale	Illinois	United States	60521
6	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
7	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
8	Montefiore Medical Center	Bronx	New York	United States	10467
9	Roswell Park Cancer Center	Buffalo	New York	United States	14263
10	Lenox Hill Hospital	New York	New York	United States	10075
11	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
12	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
13	Spartanburg Regional Healthcare / Gibbs Cancer Center	Spartanburg	South Carolina	United States	29303
14	Methodist Hospital Dallas	Dallas	Texas	United States	75203
15	St. Mark's Hospital	Salt Lake City	Utah	United States	84124
16	Fletcher Allen Health Care	Burlington	Vermont	United States	05405
17	West Virginia University Healthcare	Morgantown	West Virginia	United States	26506
18	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
19	Border Medical Oncology Research Unit	Albury	New South Wales	Australia	2640
20	Gosford Hospital	Gosford	New South Wales	Australia	2250
21	Southern Medical Day Care Centre	Wollongong	New South Wales	Australia	2500
22	Royal Brisbane Hospital	Herston	Queensland	Australia	4029
23	Gold Coast Health Services District	Southport	Queensland	Australia	4215
24	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
25	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
26	Hobart Hospital	Hobart	Tasmania	Australia	7000
27	Monash Medical Centre	Bentleigh East	Victoria	Australia	3165
28	Box Hill Hospital	Box Hill	Victoria	Australia	3128
29	Western Hospital	Footscray	Victoria	Australia	3011
30	Peninsula Oncology Centre	Frankston	Victoria	Australia	3199
31	South Eastern Hospital	Noble Park	Victoria	Australia	3174
32	Maroondah Hospital	Ringwood East	Victoria	Australia	3135
33	St. John of God Murdoch Hospital	Murdoch	Western Australia	Australia	6150
34	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
35	Royal Perth Hospital	Perth	Western Australia	Australia	6000
36	OL Vrouw Ziekenhuis	Aalst		Belgium	9300
37	Institut Jules Bordet	Brussels		Belgium	1000
38	University of Antwerp	Edegem		Belgium	2650
39	Universiteits Ziekenhuis Gent - Dienst Digestieve Oncologie	Gent		Belgium	1K12IE
40	AZ Maria Middelaress	Gent		Belgium	9000
41	CHU Sart Tilman	Liege		Belgium	4000
42	CHU Amiens	Amiens Cedex 1		France	80054
43	Centre Hospitalier General de Longjumeau	Clichy Cedex		France	92118
44	Hopital Beaujon	Clichy Cedex		France	92118
45	Hopital Albert Michallon - Grenoble	Grenoble Cedex 9		France	38043
46	Hopital Europeen Georges Pompidou	Paris		France	75015
47	CHU de Bordeaux - Hopital Saint Andre	Pessac		France	33604
48	CHU de Poitiers, Pole regional de cancerologie	Poitiers cedex		France	86021
49	Centre Eugene Marquis	Rennes Cedex		France	35042
50	Vivantes Klinikum Neukolln Klinik fur Innere Medizin - Hamatologie und Onkologie	Berlin		Germany	12351
51	SLK-Kliniken Heilbronn GmbH, Klinik fur Radiologie	Heilbronn		Germany	74078
52	Stadtisches Klinikum Karlsruheg GMBH Klinik fur Nuklearmedizin	Karlsruhe		Germany	76133
53	Schwerpunktpraxix fur Hamatologie und Onkologie	Magdeburg		Germany	39104
54	Universitaetsklinikum Magdeburg, Klinik fur Radiologie und Nuklearmedizin	Magdeburg		Germany	39120
55	Klinikum Magdeburg GmbH, Klinik fur Allgemein und Viszeralchirurgie	Magdeburg		Germany	39130
56	Universitatsklinikum Marburg Klinik fur Hamatologie, Onkologie und Immunologie	Marburg		Germany	35043
57	St. Franziskus Hospital Muenster	Muenster		Germany	48145
58	Klinikum rechts der Isar der TU Munchen Medizinische Klinik II	Munchen		Germany	81675
59	Klinikum der Universitat Munchen	Munich		Germany	81377
60	Rambam Medical Center	Haifa		Israel	31096
61	Shaare-Zedek Medical Center	Jerusalem		Israel	91031
62	Hadassah Medical Center	Jerusalem		Israel	91120
63	TA Sourasky Medical Center, Oncology Department 6	Tel Aviv		Israel	64239
64	Sheba Medical Center - Governmental Hospital - Oncology Division	Tel Hashomer		Israel	56261
65	Ospedale Regionale U. Parini	Aosta		Italy	11100
66	Dipartimento di Oncologia, Ospendali Riuniti di Bergamo	Bergamo		Italy	24127
67	A.O.U. die Bologna	Bologna		Italy	40138
68	Ufficio Sperimentale Cliniche, Oncologia Medica di Carle, Ospendale Santa Croce e Carle di Cuneo	Cuneo		Italy	12100
69	U.O. Oncologia Medica II, Nuovo Ospendale Santa Chiara, Azienda Ospendaliero Universitaria Pisana, Presidio Ospendaliero di Cisanello	Pisa		Italy	56124
70	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
71	Korea University Anam Hospital	Seoul		Korea, Republic of	136-705
72	Seoul St. Mary's Hospital	Seoul		Korea, Republic of	137-701
73	Wellington Hospital	Newtown	Wellington	New Zealand	6021
74	Dunedin Hospital	Dunedin		New Zealand	9016
75	Auckland University	Grafton		New Zealand	1023
76	Regional Cancer Treatment Service	Palmerston North		New Zealand	4414
77	Instituto Portugues de Oncologia do Porto Francisco Gentil, E.P.E.	Porto		Portugal	4200-072
78	National Cancer Centre Singapore	Singapore		Singapore	169610
79	Hospital Universitario Puerta de Hierro Majadahonda	Madrid		Spain	28222
80	Clinica Universidad de Navarra	Pamplona		Spain	31008
81	Complejo Hospitalario de Navarra	Pamplona		Spain	31008
82	National Taiwan University Hospital	Taipei		Taiwan	10048
83	Taipei Veterans General Hospital	Taipei		Taiwan	11217

Sponsors and Collaborators

• Sirtex Medical

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sirtex Medical
• ClinicalTrials.gov Identifier: NCT01721954
• Other Study ID Numbers: STX0112
• First Posted: Nov 6, 2012
• Last Update Posted: Nov 5, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sirtex Medical: colon; rectum; metastatic colorectal cancer; liver metastases
• Additional relevant MeSH terms: Colorectal Neoplasms

Study Results

Participant Flow

Recruitment Details	Between 01May2013&24Dec2014,209 patients were screened&randomised from 87centres in Australia, Belgium,France, Germany, Israel, Italy, Korea, New Zealand, Portugal, Singapore, Spain,Taiwan &the US. 209 patients randomized in the Intent to treat (ITT) population. 5 patients who did not receive study medication were not included in safety population.

Arm/Group Title	mFOLFOX6 Plus SIRT	mFOLFOX6 Alone
Arm/Group Description	Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab plus SIR-Spheres microspheres. FOLFOX6m SIR-Spheres microspheres	Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab repeated every two weeks until evidence of treatment failure. FOLFOX6m
Period Title: Overall Study
STARTED	105	104
COMPLETED	35	35
NOT COMPLETED	70	69

Baseline Characteristics

Arm/Group Title	mFOLFOX6 Plus SIRT	mFOLFOX6 Alone	Total
Arm/Group Description	Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab plus SIR-Spheres microspheres. FOLFOX6m SIR-Spheres microspheres	Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab repeated every two weeks until evidence of treatment failure. FOLFOX6m	Total of all reporting groups
Overall Participants	105	104	209
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.6 (11.28)	62.4 (10.06)	62.5 (10.66)
Age, Customized (Count of Participants)
Below 65 years	60 57.1%	57 54.8%	117 56%
Greater than or equal to 65 years	45 42.9%	47 45.2%	92 44%
Sex: Female, Male (Count of Participants)
Female	41 39%	44 42.3%	85 40.7%
Male	64 61%	60 57.7%	124 59.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	8 7.6%	6 5.8%	14 6.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 3.8%	2 1.9%	6 2.9%
White	88 83.8%	93 89.4%	181 86.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	5 4.8%	3 2.9%	8 3.8%
WHO performance status (Count of Participants)
0	61 58.1%	53 51%	114 54.5%
1	44 41.9%	50 48.1%	94 45%
Unknown	0 0%	1 1%	1 0.5%
Extra-hepatic Disease (participants) [Number]
Yes	32 30.5%	27 26%	59 28.2%
No	73 69.5%	77 74%	150 71.8%
Liver Involvement % (participants) [Number]
<=25%	74 70.5%	74 71.2%	148 70.8%
>25%	31 29.5%	30 28.8%	61 29.2%
Tumor volume (percentage of liver) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of liver]	18.5 (17.77)	17.9 (16.18)	18.2 (16.96)
ITT bevacizumab (Count of Participants)
Yes	87 82.9%	87 83.7%	174 83.3%
No	18 17.1%	17 16.3%	35 16.7%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	OS defined as the time interval between the date of randomization and the date of death from any cause.
Time Frame	From date of randomization until the date of death from any cause assessed up 3 yrs 8 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	mFOLFOX6 Plus SIRT	mFOLFOX6 Alone
Arm/Group Description	Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab plus SIR-Spheres microspheres. FOLFOX6m SIR-Spheres microspheres	Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab repeated every two weeks until evidence of treatment failure. FOLFOX6m
Measure Participants	105	104
Median (95% Confidence Interval) [months]	25.9	25.0

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 overall survival (months) of SIRT/FOLFOX treatment versus FOLFOX is equal for both groups. The two-sided alternative hypothesis tested with 95% confidence is OS time for SIRT/FOLFOX treatment lower to that of FOLFOX.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression-free Survival
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 3 years 8 months.

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	mFOLFOX6 Plus SIRT	mFOLFOX6 Alone
Arm/Group Description	Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab plus SIR-Spheres microspheres. FOLFOX6m SIR-Spheres microspheres	Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab repeated every two weeks until evidence of treatment failure. FOLFOX6m
Measure Participants	105	104
Median (95% Confidence Interval) [months]	11.8	11.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	mFOLFOX6 Plus SIRT, mFOLFOX6 Alone
	Comments	A sample size of at least 209 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 14.5 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 209. 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) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From consent until 28 days post last dose of protocol chemotherapy, an average of 3 years 8 months.
Adverse Event Reporting Description	Adverse Events monitored for all participants who were randomized and received at least 1 cycle of study treatment. Of the 105 in 'mFOLFOX6 Plus SIRT' arm, 3 did not get any treatment,10 received mFOLFOX6 without SIRT. Hence safety population in this arm comprises 92 participants. The 'mFOLFOX6 alone' arm comprised 104 participants, 2 did not receive any treatment and safety population in this arm comprises 112 participants including the 10 participants that received mFOLFOX6 without SIRT.
Arm/Group Title	mFOLFOX6 Plus SIRT		mFOLFOX6 Alone
Arm/Group Description	Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab plus SIR-Spheres microspheres. FOLFOX6m SIR-Spheres microspheres		Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab repeated every two weeks until evidence of treatment failure. FOLFOX6m
All Cause Mortality
	mFOLFOX6 Plus SIRT		mFOLFOX6 Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/92 (63%)		64/112 (57.1%)
Serious Adverse Events
	mFOLFOX6 Plus SIRT		mFOLFOX6 Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/92 (51.1%)		47/112 (42%)
Blood and lymphatic system disorders
Febrile Neutropenia	10/92 (10.9%)		3/112 (2.7%)
Neutropenia	2/92 (2.2%)		1/112 (0.9%)
Pancytopenia	2/92 (2.2%)		0/112 (0%)
Cardiac disorders
Acute Myocardial Infarction	1/92 (1.1%)		0/112 (0%)
Arteriospasm Coronary	1/92 (1.1%)		1/112 (0.9%)
Cardiac Failure	0/92 (0%)		1/112 (0.9%)
Cardiotoxicity	1/92 (1.1%)		0/112 (0%)
Eye disorders
Retinal Detachment	0/92 (0%)		1/112 (0.9%)
Vitreous Haemorrhage	1/92 (1.1%)		0/112 (0%)
Gastrointestinal disorders
Abdominal Pain	9/92 (9.8%)		0/112 (0%)
Abdominal Pain Upper	0/92 (0%)		1/112 (0.9%)
Anal Fissure	0/92 (0%)		1/112 (0.9%)
Colitis	0/92 (0%)		1/112 (0.9%)
Diarrhoea	5/92 (5.4%)		5/112 (4.5%)
Duodenal Perforation	1/92 (1.1%)		0/112 (0%)
Duodenal Ulcer Haemorrhage	0/92 (0%)		1/112 (0.9%)
Enterocolitis	1/92 (1.1%)		0/112 (0%)
Gastric Ulcer	2/92 (2.2%)		0/112 (0%)
Gastritis	1/92 (1.1%)		0/112 (0%)
Gastrointestinal Haemorrhage	1/92 (1.1%)		0/112 (0%)
Haematemesis	1/92 (1.1%)		0/112 (0%)
Intestinal Obstruction	1/92 (1.1%)		2/112 (1.8%)
Intestinal Perforation	0/92 (0%)		1/112 (0.9%)
Large Intestinal Obstruction	0/92 (0%)		1/112 (0.9%)
Large Intestine Perforation	0/92 (0%)		1/112 (0.9%)
Nausea	1/92 (1.1%)		0/112 (0%)
Neutropenic Colitis	0/92 (0%)		1/112 (0.9%)
Pancreatitis	2/92 (2.2%)		0/112 (0%)
Small Intestinal Obstruction	0/92 (0%)		1/112 (0.9%)
Varices Oesophageal	0/92 (0%)		1/112 (0.9%)
Vomiting	1/92 (1.1%)		1/112 (0.9%)
Constipation	1/92 (1.1%)		0/112 (0%)
General disorders
Asthenia	1/92 (1.1%)		0/112 (0%)
Chest Pain	1/92 (1.1%)		0/112 (0%)
Fatigue	1/92 (1.1%)		0/112 (0%)
General Physical Health Deterioration	2/92 (2.2%)		2/112 (1.8%)
Malaise	1/92 (1.1%)		1/112 (0.9%)
Mucosal Inflammation	2/92 (2.2%)		0/112 (0%)
Pain	1/92 (1.1%)		0/112 (0%)
Pyrexia	2/92 (2.2%)		3/112 (2.7%)
Hepatobiliary disorders
Cholelithiasis	1/92 (1.1%)		0/112 (0%)
Hepatic Cirrhosis	1/92 (1.1%)		0/112 (0%)
Hepatic Failure	2/92 (2.2%)		0/112 (0%)
Hyperbilirubinaemia	1/92 (1.1%)		0/112 (0%)
Portal Hypertension	0/92 (0%)		1/112 (0.9%)
Infections and infestations
Abdominal Sepsis	0/92 (0%)		1/112 (0.9%)
Anal Abscess	0/92 (0%)		1/112 (0.9%)
Campylobacter Gastroenteritis	1/92 (1.1%)		0/112 (0%)
Cellulitis	1/92 (1.1%)		0/112 (0%)
Clostridium Difficile Infection	1/92 (1.1%)		0/112 (0%)
Device Related Infection	1/92 (1.1%)		1/112 (0.9%)
Device Related Sepsis	0/92 (0%)		1/112 (0.9%)
Enteritis Infectious	0/92 (0%)		1/112 (0.9%)
Enterococcal Sepsis	1/92 (1.1%)		0/112 (0%)
Escherichia Sepsis	2/92 (2.2%)		0/112 (0%)
Escherichia Urinary Tract Infection	1/92 (1.1%)		0/112 (0%)
Infection	1/92 (1.1%)		1/112 (0.9%)
Infusion Site Cellulitis	1/92 (1.1%)		0/112 (0%)
Infusion Site Infection	0/92 (0%)		1/112 (0.9%)
Lower Respiratory Tract Infection	1/92 (1.1%)		1/112 (0.9%)
Lung Abscess	0/92 (0%)		1/112 (0.9%)
Neutropenic Sepsis	1/92 (1.1%)		0/112 (0%)
Pelvic Abscess	1/92 (1.1%)		0/112 (0%)
Peritonitis	1/92 (1.1%)		0/112 (0%)
Peritonitis Bacterial	1/92 (1.1%)		0/112 (0%)
Pneumonia	6/92 (6.5%)		3/112 (2.7%)
Pseudomonal Bacteraemia	1/92 (1.1%)		0/112 (0%)
Rectal Abscess	1/92 (1.1%)		0/112 (0%)
Respiratory Tract Infection	0/92 (0%)		1/112 (0.9%)
Sepsis	2/92 (2.2%)		2/112 (1.8%)
Skin Bacterial Infection	1/92 (1.1%)		0/112 (0%)
Upper Respiratory Tract Infection	1/92 (1.1%)		0/112 (0%)
Urinary Tract Infection	2/92 (2.2%)		2/112 (1.8%)
Injury, poisoning and procedural complications
Arterial Injury	1/92 (1.1%)		0/112 (0%)
Gastrointestinal Stoma Complication	0/92 (0%)		2/112 (1.8%)
Hip Fracture	1/92 (1.1%)		0/112 (0%)
Intestinal Anastomosis Complication	0/92 (0%)		1/112 (0.9%)
Thermal Burn	0/92 (0%)		1/112 (0.9%)
Investigations
C-Reactive Protein Increased	0/92 (0%)		1/112 (0.9%)
White Blood Cell Count Decreased	1/92 (1.1%)		0/112 (0%)
Metabolism and nutrition disorders
Dehydration	4/92 (4.3%)		0/112 (0%)
Diabetic Complication	0/92 (0%)		1/112 (0.9%)
Diabetic Ketoacidosis	0/92 (0%)		1/112 (0.9%)
Hypercalcaemia	1/92 (1.1%)		0/112 (0%)
Hyperglycaemia	0/92 (0%)		2/112 (1.8%)
Hypokalaemia	1/92 (1.1%)		1/112 (0.9%)
Musculoskeletal and connective tissue disorders
Back Pain	0/92 (0%)		2/112 (1.8%)
Groin Pain	0/92 (0%)		1/112 (0.9%)
Muscle Haemorrhage	1/92 (1.1%)		0/112 (0%)
Pain In Extremity	0/92 (0%)		1/112 (0.9%)
Pathological Fracture	0/92 (0%)		1/112 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases To Meninges	0/92 (0%)		1/112 (0.9%)
Nervous system disorders
Hepatic Encephalopathy	2/92 (2.2%)		0/112 (0%)
Mental Impairment	1/92 (1.1%)		0/112 (0%)
Presyncope	0/92 (0%)		1/112 (0.9%)
Syncope	1/92 (1.1%)		1/112 (0.9%)
Psychiatric disorders
Acute Psychosis	1/92 (1.1%)		0/112 (0%)
Confusional State	1/92 (1.1%)		2/112 (1.8%)
Delirium	1/92 (1.1%)		1/112 (0.9%)
Renal and urinary disorders
Renal Failure Acute	0/92 (0%)		1/112 (0.9%)
Renal Injury	0/92 (0%)		1/112 (0.9%)
Urinary Retention	1/92 (1.1%)		0/112 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/92 (1.1%)		0/112 (0%)
Dyspnoea	1/92 (1.1%)		1/112 (0.9%)
Epistaxis	0/92 (0%)		1/112 (0.9%)
Haemoptysis	0/92 (0%)		1/112 (0.9%)
Pneumonia Aspiration	0/92 (0%)		1/112 (0.9%)
Pneumonitis	0/92 (0%)		1/112 (0.9%)
Pulmonary Embolism	5/92 (5.4%)		0/112 (0%)
Skin and subcutaneous tissue disorders
Decubitus Ulcer	1/92 (1.1%)		0/112 (0%)
Vascular disorders
Artery Dissection	1/92 (1.1%)		0/112 (0%)
Deep Vein Thrombosis	0/92 (0%)		1/112 (0.9%)
Jugular Vein Thrombosis	0/92 (0%)		1/112 (0.9%)
Orthostatic Hypotensio	1/92 (1.1%)		1/112 (0.9%)
Peripheral Artery Thrombosis	1/92 (1.1%)		0/112 (0%)
Vena Cava Thrombosis	0/92 (0%)		1/112 (0.9%)
Other (Not Including Serious) Adverse Events
	mFOLFOX6 Plus SIRT		mFOLFOX6 Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	92/92 (100%)		111/112 (99.1%)
Blood and lymphatic system disorders
Neutropenia	43/92 (46.7%)		46/112 (41.1%)
Thrombocytopenia	39/92 (42.4%)		11/112 (9.8%)
Anaemia	21/92 (22.8%)		15/112 (13.4%)
Leukopenia	13/92 (14.1%)		10/112 (8.9%)
Lymphopenia	6/92 (6.5%)		1/112 (0.9%)
Eye disorders
Lacrimation Increased	2/92 (2.2%)		6/112 (5.4%)
Gastrointestinal disorders
Nausea	46/92 (50%)		55/112 (49.1%)
Diarrhoea	35/92 (38%)		59/112 (52.7%)
Constipation	39/92 (42.4%)		45/112 (40.2%)
Abdominal Pain	33/92 (35.9%)		24/112 (21.4%)
Vomiting	24/92 (26.1%)		33/112 (29.5%)
Stomatitis	21/92 (22.8%)		29/112 (25.9%)
Abdominal Pain Upper	20/92 (21.7%)		12/112 (10.7%)
Gastrooesophageal Reflux Disease	7/92 (7.6%)		14/112 (12.5%)
Mouth Ulceration	4/92 (4.3%)		14/112 (12.5%)
Abdominal Distension	9/92 (9.8%)		7/112 (6.3%)
Rectal Haemorrhage	7/92 (7.6%)		7/112 (6.3%)
Dry Mouth	3/92 (3.3%)		9/112 (8%)
Ascites	9/92 (9.8%)		1/112 (0.9%)
Dyspepsia	5/92 (5.4%)		5/112 (4.5%)
Gastritis	5/92 (5.4%)		1/112 (0.9%)
General disorders
Fatigue	48/92 (52.2%)		49/112 (43.8%)
Mucosal Inflammation	12/92 (13%)		23/112 (20.5%)
Asthenia	15/92 (16.3%)		18/112 (16.1%)
Pyrexia	17/92 (18.5%)		16/112 (14.3%)
Oedema Peripheral	13/92 (14.1%)		6/112 (5.4%)
Pain	3/92 (3.3%)		8/112 (7.1%)
Chest Pain	1/92 (1.1%)		8/112 (7.1%)
Infections and infestations
Urinary Tract Infection	9/92 (9.8%)		10/112 (8.9%)
Upper Respiratory Tract Infection	10/92 (10.9%)		8/112 (7.1%)
Nasopharyngitis	2/92 (2.2%)		8/112 (7.1%)
Bronchitis	1/92 (1.1%)		6/112 (5.4%)
Injury, poisoning and procedural complications
Contusion	5/92 (5.4%)		3/112 (2.7%)
Fall	5/92 (5.4%)		2/112 (1.8%)
Investigations
Weight Decreased	29/92 (31.5%)		19/112 (17%)
Neutrophil Count Decreased	7/92 (7.6%)		8/112 (7.1%)
Weight Increased	5/92 (5.4%)		9/112 (8%)
Platelet Count Decreased	9/92 (9.8%)		4/112 (3.6%)
Aspartate Aminotransferase Increased	9/92 (9.8%)		2/112 (1.8%)
Blood Alkaline Phosphatase Increased	6/92 (6.5%)		5/112 (4.5%)
White Blood Cell Count Decreased	7/92 (7.6%)		4/112 (3.6%)
Blood Bilirubin Increased	5/92 (5.4%)		3/112 (2.7%)
Alanine Aminotransferase Increased	6/92 (6.5%)		1/112 (0.9%)
Blood Albumin Decreased	5/92 (5.4%)		2/112 (1.8%)
Metabolism and nutrition disorders
Decreased Appetite	25/92 (27.2%)		30/112 (26.8%)
Hypokalaemia	11/92 (12%)		13/112 (11.6%)
Dehydration	5/92 (5.4%)		7/112 (6.3%)
Hypomagnesaemia	3/92 (3.3%)		9/112 (8%)
Hyperglycaemia	5/92 (5.4%)		6/112 (5.4%)
Hypoalbuminaemia	8/92 (8.7%)		3/112 (2.7%)
Musculoskeletal and connective tissue disorders
Back Pain	9/92 (9.8%)		14/112 (12.5%)
Musculoskeletal Pain	5/92 (5.4%)		12/112 (10.7%)
Pain In Extremity	13/92 (14.1%)		4/112 (3.6%)
Arthralgia	3/92 (3.3%)		8/112 (7.1%)
Muscle Spasms	3/92 (3.3%)		7/112 (6.3%)
Nervous system disorders
Neuropathy peripheral	54/92 (58.7%)		55/112 (49.1%)
Peripheral sensory neuropathy	16/92 (17.4%)		29/112 (25.9%)
Headache	13/92 (14.1%)		21/112 (18.8%)
Paraesthesia	15/92 (16.3%)		19/112 (17%)
Dysgeusia	17/92 (18.5%)		10/112 (8.9%)
Dizziness	8/92 (8.7%)		6/112 (5.4%)
Psychiatric disorders
Insomnia	16/92 (17.4%)		15/112 (13.4%)
Anxiety	8/92 (8.7%)		12/112 (10.7%)
Renal and urinary disorders
Dysuria	1/92 (1.1%)		6/112 (5.4%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	20/92 (21.7%)		27/112 (24.1%)
Cough	12/92 (13%)		13/112 (11.6%)
Dyspnoea	10/92 (10.9%)		12/112 (10.7%)
Dysphonia	3/92 (3.3%)		10/112 (8.9%)
Oropharyngeal Pain	3/92 (3.3%)		8/112 (7.1%)
Rhinorrhoea	4/92 (4.3%)		7/112 (6.3%)
Pulmonary Embolism	3/92 (3.3%)		7/112 (6.3%)
Hiccups	7/92 (7.6%)		0/112 (0%)
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome	11/92 (12%)		19/112 (17%)
Rash	13/92 (14.1%)		11/112 (9.8%)
Alopecia	7/92 (7.6%)		15/112 (13.4%)
Dry Skin	4/92 (4.3%)		11/112 (9.8%)
Pruritus	2/92 (2.2%)		7/112 (6.3%)
Vascular disorders
Hypertension	15/92 (16.3%)		28/112 (25%)

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.