Phase 3 Trial of Litx™ Plus Chemotherapy vs. Chemotherapy Only Treating Colorectal Cancer Patients With Recurrent Liver Metastases

• Sponsor: Light Sciences Oncology (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00440310
• Collaborator: (none)
• Enrollment: 483
• Locations: 57
• Arms: 2
• Duration (Months): 56
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of the study is to assess the overall survival and progression free survival of patients treated with Litx™ + chemotherapy versus chemotherapy alone in the treatment of Colorectal Cancer with recurrent liver metastases, and to demonstrate the safety of Litx™ therapy.

Litx™ consists of a light-activated drug, talaporfin sodium (LS11, Light Sciences Oncology, Bellevue, Washington), and a light generating device, composed of light-emitting diodes (LEDs), that is energized by a power controller and percutaneously placed in the target tumor tissue inside the body.

Condition or Disease	Intervention/Treatment	Phase
Liver Metastases; Colorectal Neoplasms; Neoplasm Metastasis; Neoplasm Recurrence, Local	Drug: Talaporfin sodium; Procedure: Percutaneous placement of device in liver metastases; Device: Interstitial light emitting diodes; Drug: FOLFOX4 regimen; Drug: FOLFIRI regimen	Phase 3

Detailed Description

Randomized, stratified, two arm study:

• Litx™ and chemotherapy arm (FOLFOX4 or FOLFIRI)

• Chemotherapy only arm (FOLFOX4 or FOLFIRI)

For patients who have progressed on FOLFIRI, they will be treated with Litx™ plus FOLFOX4 versus FOLFOX4 alone; and for patients who have progressed on FOLFOX, they will be treated with Litx™ plus FOLFIRI versus FOLFIRI alone.

Stratification upon enrollment by chemotherapy and tumor sum of the longest diameter (SLD) (SLD < 4 cm or SLD ≥4 cm but ≤7.5 cm).

Study Design

• Study Type: Interventional
• Actual Enrollment: 483 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Multinational Phase 3 Randomized Study to Evaluate the Safety and Efficacy of Treating Colorectal Cancer Patients With Recurrent Liver Metastases Using the Litx™ System Plus Chemotherapy as Compared to Chemotherapy Only
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Litx + Chemotherapy	Drug: Talaporfin sodium; LS11 (Talaporfin Sodium) dose is 1mg/kg administered intravenously slow push (3-5 minutes).; Procedure: Percutaneous placement of device in liver metastases; Light Source placement will be conducted under placement imaging using ultrasound or CT guidance. No more than four Light Sources will be used at a single treatment session. The Light Sources may be used in a single lesion or in multiple lesions.; Device: Interstitial light emitting diodes; 200 J/cm per Light Source at 20 mW/cm light energy; Drug: FOLFOX4 regimen; Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin; Drug: FOLFIRI regimen; Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan
Active Comparator: Chemotherapy alone	Drug: FOLFOX4 regimen; Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin; Drug: FOLFIRI regimen; Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan

Outcome Measures

Primary Outcome Measures

1. Overall Survival [Up to 184 weeks]

   Time from randomization to death

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with recurrent metastatic liver lesions from colorectal cancer who progressed on either FOLFOX or FOLFIRI

• Biopsy proven evidence of colorectal cancer

• At least one liver lesion that can be measured in one dimension at >10 mm with spiral CT scan (CT preferred but MRI allowed)

• ECOG Performance Status 0-2

• Life expectancy of at least 16 weeks

• At least 30 days must have elapsed since the completion of any prior antineoplastic therapy and the patient must have recovered from acute side effects before day 0

• Understanding and ability to sign written informed consent

• 18 years of age or more

• Adequate hematologic, liver and renal functions as evidenced by the following: WBC > 2.5 × 10^{9/L ; Platelet Count > 100 × 10}9/L ; Hemoglobin > 90 g/L ; Neutrophils >1.5 × 10^9/L ; PT and PTT < 1.5 Control ; SGOT, SGPT < 5 × ULN ; GGT < 5 × ULN ; Alkaline phosphatase < 5 × ULN ; Bilirubin < 3 × ULN ; Creatinine < 1.5 × ULN

Exclusion Criteria:

• Patients who are candidates for complete surgical resection

• Patients who received bevacizumab (Avastin®) or cetuximab (Erbitux®) within 30 days of randomization. Use of bevacizumab or cetuximab is prohibited while participating in this study

• Patients who would require more than a total number of 12 light source applications over three Litx™ experimental treatments (no more than 4 light sources per treatment).

• Patients who have a single measurable tumor greater than 7.5 cm in any organ

• Target lesions irradiated within 3 months of randomization

• Patients with tumor involvement in greater than 50% of parenchyma of the liver

• Evidence of major vessel invasion of any organ

• Patients with any non-colorectal cancers except for adequately treated basal or squamous cell skin cancer, or adequately treated stage I or II cancer from which the patient has been disease-free for ≥ 3 years, or other cancer from which the patient has been disease-free for ≥ 5 years

• Known sensitivity to porphyrin-type drugs or known history of porphyria

• Pregnancy or breast-feeding patients. A negative pregnancy test (urine or serum) from women of childbearing age is required prior to enrollment. A fertile patient must use effective contraception during participation in the study

• Concurrent participation in another clinical trial involving experimental treatment

• Any concurrent disease or condition that in the opinion of the investigator impairs the patient's ability to complete the trial such as psychological, familial, sociological, geographical or medical conditions which in the Principal Investigator's opinion could compromise compliance with the objectives and procedures of this protocol or obscure interpretation of the trial's data.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Landeskrankenhaus Feldkirch	Feldkirch		Austria
2	Krankenhaus Hietzing mit Neurologischen Zentrum Rosenhugel	Wien		Austria
3	Clinical Hospital Mostar, Internal Clinic, Department of Gastroenterology	Mostar		Bosnia and Herzegovina
4	Clinical Centre of the University of Sarajevo, Institute of Oncology	Sarajevo		Bosnia and Herzegovina
5	General Hospital Karlovac	Karlovac		Croatia
6	Clinical Centre Zagreb, Clinical Oncology	Zagreb		Croatia
7	General Hospital "Sveti Duh"	Zagreb		Croatia
8	University Hospital Dubrava	Zagreb		Croatia
9	Ostalb-Klinikum Aalen Darmzentrum Medizinische Klinik I	Aalen		Germany
10	Helios Kliniken - Innere Medizin und Kardiologie	Borna		Germany
11	Katholisches Krankenhaus St. Johann Nepomuk	Erfurt		Germany
12	Johann Wolfgang Goethe Universitat	Frankfurt		Germany
13	Kliniken Ludwigsburg Bietigheim	Ludwigsburg		Germany
14	Bangalore Institute of Oncology	Bangalore	Karnataka	India
15	Mahavir Cancer Sansthan	Phulwarisharif	Patna	India
16	CIIGMA Institute of Medical Sciences	Aurangabad		India
17	Jawaharlal Nehru Cancer Hospital and Research Centre	Bhopal		India
18	SEAROC Cancer Center, S. K. Soni hospital	Jaipur		India
19	Shatabdi Super Specialty Hospital	Mumbai		India
20	Cancer Clinic, Shreevardhan complex	Nagpur		India
21	Ruby Hall Clinic	Pune		India
22	Azienda Ospedaliero-Universitaria Riunti	Ancona		Italy
23	Azienda Ospedaliera Careggi U.O. Oncologia Medica	Firenze		Italy
24	Azienda Ospedaliera Universitaria Padovana	Padova		Italy
25	Policlinico Tor Vergata - Oncologia Medica	Rome		Italy
26	Riga Eastern Hospital, Latvian Oncology Center	Riga		Latvia
27	Centrum Onkologii - Instytut im. Marii Skłodowskiej -Curie Oddział w Krakowie	Kraków		Poland
28	Szpital Uniwersytecki CMUJ, Klinika Chirurgii Ogólnej i Gastroenterologicznej	Kraków		Poland
29	Klinika Chirurgii Onkologicznej	Lublin		Poland
30	Zakład Opieki Zdrowotnej MSWiA z Warmińsko-Mazurskim Centrum Onkologii	Olsztyn		Poland
31	Klinika Chirurgii Ogólnej i Onkologicznej	Szczecin		Poland
32	Centrum Onkologii - Instytut im. Marii Skłodowskiej -Curie, Klinika Nowotworów Jelita Grubego	Warszawa		Poland
33	Szpital Wojewódzki im. M. Kopernika, Klinika Chemioterapii Onkologicznej	Łódź		Poland
34	Fundeni Clinical Institute	Bucharest		Romania
35	Oncology Institute "Ion Chircuta"	Cluj-Napoca		Romania
36	St. Spiridon University Emergency Hospital	Iasi		Romania
37	State Institution "Altay" Territorial Oncological Dispensary	Barmaul		Russian Federation
38	State Healthcare Institution "Sverdlovsk' Regional Oncological Dispensary"	Ekaterinburg		Russian Federation
39	Main Military Clinical Hospital named after Burdenko attached to Ministry of Defense of Russian Federation	Moscow		Russian Federation
40	Municipal Cliical Hospital # 33 named after Ostroumov	Moscow		Russian Federation
41	Russian Oncological Scientific Center named after Blokhin	Moscow		Russian Federation
42	Privolzhsky District Medical Center	Nizhny Novgorod		Russian Federation
43	Central Research Institute of Roentgenology and Radiology	St. Petersburg		Russian Federation
44	Scientific Research Institution of Oncology	St. Petersburg		Russian Federation
45	State Educational Institution of High Professional Education "Military-Medical Academy named after S.M. Kirov attached to Ministry of Defense of Russia"	St. Petersburg		Russian Federation
46	Tambov Regional Oncological Dispensary	Tambov		Russian Federation
47	State Healthcare Institution of Yaroslavl region, "Regional clinical oncological hospital"	Yaroslavl		Russian Federation
48	Institute of Oncology and Radiology of Serbia	Belgrade		Serbia
49	Military Medical Academy	Belgrade		Serbia
50	Institute of Oncology	Sremska Kamenica		Serbia
51	Karolinska University Hospital	Stockholm		Sweden
52	Municipal Institution "Cherkassy" Regional Oncological Dispensary of Cherkassy	Cherkassy		Ukraine
53	Municipal Multiple-Discipline Clinical Hospital #4	Dnepropetrovsk		Ukraine
54	Donetsk Cancer Centre	Donetsk		Ukraine
55	Kharkov Regional Clinical Oncology Dispansery	Kharkov		Ukraine
56	The Central Hospital of the Ministry of Defense	Kyiv		Ukraine
57	Zaporozhye Medical Academy for postgraduate education	Zaporozhye		Ukraine

Sponsors and Collaborators

• Light Sciences Oncology

Investigators

• Study Director: Sy-Shi Wang, PhD, Light Sciences Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Light Sciences Oncology
• ClinicalTrials.gov Identifier: NCT00440310
• Other Study ID Numbers: LSO-OL006
• First Posted: Feb 27, 2007
• Last Update Posted: Aug 25, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Light Sciences Oncology: Liver neoplasms; Liver metastases; MCRC; Litx™; LS11; Colorectal cancer with recurrent liver metastases
• Additional relevant MeSH terms: Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis; Neoplasms, Second Primary; Liver Neoplasms; Neoplasm Recurrence, Local; Recurrence; Talaporfin

Study Results

Participant Flow

Arm/Group Title	Litx + Chemotherapy	Chemotherapy Alone
Arm/Group Description	Talaporfin sodium: LS11 (Talaporfin Sodium) dose is 1mg/kg administered intravenously slow push (3-5 minutes). Percutaneous placement of device in liver metastases: Light Source placement will be conducted under placement imaging using ultrasound or CT guidance. No more than four Light Sources will be used at a single treatment session. The Light Sources may be used in a single lesion or in multiple lesions. Interstitial light emitting diodes: 200 J/cm per Light Source at 20 mW/cm light energy FOLFOX4 regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin FOLFIRI regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan	FOLFOX4 regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin FOLFIRI regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan
Period Title: Overall Study
STARTED	244	239
Treated	222	232
COMPLETED	216	209
NOT COMPLETED	28	30

Baseline Characteristics

Arm/Group Title	Litx + Chemotherapy	Chemotherapy Alone	Total
Arm/Group Description	Talaporfin sodium: LS11 (Talaporfin Sodium) dose is 1mg/kg administered intravenously slow push (3-5 minutes). Percutaneous placement of device in liver metastases: Light Source placement will be conducted under placement imaging using ultrasound or CT guidance. No more than four Light Sources will be used at a single treatment session. The Light Sources may be used in a single lesion or in multiple lesions. Interstitial light emitting diodes: 200 J/cm per Light Source at 20 mW/cm light energy FOLFOX4 regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin FOLFIRI regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan	FOLFOX4 regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin FOLFIRI regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan	Total of all reporting groups
Overall Participants	244	239	483
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.2 (9.8)	60.1 (10.2)	59.7 (10.0)
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	60.0	61.0	60.0
Sex: Female, Male (Count of Participants)
Female	107 43.9%	97 40.6%	204 42.2%
Male	137 56.1%	142 59.4%	279 57.8%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Time from randomization to death
Time Frame	Up to 184 weeks

Outcome Measure Data

Analysis Population Description

ITT (All patient randomized/enrolled)

Arm/Group Title	Litx + Chemotherapy	Chemotherapy Alone
Arm/Group Description	Talaporfin sodium: LS11 (Talaporfin Sodium) dose is 1mg/kg administered intravenously slow push (3-5 minutes). Percutaneous placement of device in liver metastases: Light Source placement will be conducted under placement imaging using ultrasound or CT guidance. No more than four Light Sources will be used at a single treatment session. The Light Sources may be used in a single lesion or in multiple lesions. Interstitial light emitting diodes: 200 J/cm per Light Source at 20 mW/cm light energy FOLFOX4 regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin FOLFIRI regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan	FOLFOX4 regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin FOLFIRI regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan
Measure Participants	244	239
Median (Inter-Quartile Range) [Days]	390	405

Adverse Events

Arm/Group Title	Litx + Chemotherapy		Chemotherapy Alone
Arm/Group Description	Talaporfin sodium: LS11 (Talaporfin Sodium) dose is 1mg/kg administered intravenously slow push (3-5 minutes). Percutaneous placement of device in liver metastases: Light Source placement will be conducted under placement imaging using ultrasound or CT guidance. No more than four Light Sources will be used at a single treatment session. The Light Sources may be used in a single lesion or in multiple lesions. Interstitial light emitting diodes: 200 J/cm per Light Source at 20 mW/cm light energy FOLFOX4 regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin FOLFIRI regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan		FOLFOX4 regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin FOLFIRI regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan
All Cause Mortality
	Litx + Chemotherapy		Chemotherapy Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Litx + Chemotherapy		Chemotherapy Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/222 (29.7%)		52/232 (22.4%)
Blood and lymphatic system disorders
Anaemia	5/222 (2.3%)		4/232 (1.7%)
Anaemia of malignant disease	1/222 (0.5%)		0/232 (0%)
Febrile neutropenia	3/222 (1.4%)		2/232 (0.9%)
Lymphadenopathy	0/222 (0%)		1/232 (0.4%)
Neutropenia	6/222 (2.7%)		6/232 (2.6%)
Thrombocytopenia	2/222 (0.9%)		0/232 (0%)
Cardiac disorders
Cardiac arrest	0/222 (0%)		2/232 (0.9%)
Cardiac failure	1/222 (0.5%)		0/232 (0%)
Cardio-respiratory arrest	1/222 (0.5%)		1/232 (0.4%)
Congestive cardiomyopathy	0/222 (0%)		1/232 (0.4%)
Gastrointestinal disorders
Abdominal pain	1/222 (0.5%)		0/232 (0%)
Ascites	1/222 (0.5%)		0/232 (0%)
Constipation	1/222 (0.5%)		0/232 (0%)
Diarrhoea	2/222 (0.9%)		3/232 (1.3%)
Duodenal ulcer perforation	1/222 (0.5%)		0/232 (0%)
Gastric haemorrhage	0/222 (0%)		1/232 (0.4%)
Gastric ulcer haemorrhage	1/222 (0.5%)		0/232 (0%)
Gastritis	0/222 (0%)		1/232 (0.4%)
Gastrointestinal haemorrhage	1/222 (0.5%)		1/232 (0.4%)
Ileus	1/222 (0.5%)		1/232 (0.4%)
Intestinal obstruction	1/222 (0.5%)		1/232 (0.4%)
Mechanical ileus	1/222 (0.5%)		0/232 (0%)
Nausea	0/222 (0%)		1/232 (0.4%)
Rectal haemorrhage	0/222 (0%)		2/232 (0.9%)
Subileus	1/222 (0.5%)		1/232 (0.4%)
General disorders
Asthenia	3/222 (1.4%)		1/232 (0.4%)
Death	1/222 (0.5%)		0/232 (0%)
Fatigue	0/222 (0%)		1/232 (0.4%)
Mucosal inflammation	0/222 (0%)		1/232 (0.4%)
Pyrexia	4/222 (1.8%)		2/232 (0.9%)
Sudden death	3/222 (1.4%)		0/232 (0%)
Hepatobiliary disorders
Bile duct obstruction	3/222 (1.4%)		0/232 (0%)
Cholangitis	1/222 (0.5%)		0/232 (0%)
Haemobilia	1/222 (0.5%)		0/232 (0%)
Hyperbilirubinaemia	1/222 (0.5%)		0/232 (0%)
Liver injury	1/222 (0.5%)		0/232 (0%)
Immune system disorders
Hypersensitivity	2/222 (0.9%)		0/232 (0%)
Infections and infestations
Gastroenteritis	0/222 (0%)		1/232 (0.4%)
Liver abscess	2/222 (0.9%)		0/232 (0%)
Malaria	1/222 (0.5%)		0/232 (0%)
Perirectal abscess	2/222 (0.9%)		0/232 (0%)
Pneumonia	1/222 (0.5%)		1/232 (0.4%)
Sepsis	0/222 (0%)		1/232 (0.4%)
Septic shock	0/222 (0%)		1/232 (0.4%)
Injury, poisoning and procedural complications
Hip fracture	0/222 (0%)		1/232 (0.4%)
Post procedural haematoma	1/222 (0.5%)		1/232 (0.4%)
Procedural pain	8/222 (3.6%)		0/232 (0%)
Tibia fracture	0/222 (0%)		1/232 (0.4%)
Metabolism and nutrition disorders
Tumour lysis syndrome	0/222 (0%)		1/232 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone	0/222 (0%)		1/232 (0.4%)
Metastases to central nervous system	1/222 (0.5%)		1/232 (0.4%)
Metastases to perineum	0/222 (0%)		1/232 (0.4%)
Neoplasm malignant	10/222 (4.5%)		12/232 (5.2%)
Ovarian cancer	0/222 (0%)		1/232 (0.4%)
Paraneoplastic syndrome	0/222 (0%)		1/232 (0.4%)
Nervous system disorders
Cerebral ischaemia	2/222 (0.9%)		0/232 (0%)
Cerebrovascular accident	0/222 (0%)		1/232 (0.4%)
Hemiplegia	0/222 (0%)		1/232 (0.4%)
Status epilepticus	1/222 (0.5%)		0/232 (0%)
Renal and urinary disorders
Renal failure acute	1/222 (0.5%)		1/232 (0.4%)
Ureteric obstruction	1/222 (0.5%)		1/232 (0.4%)
Ureteric stenosis	0/222 (0%)		1/232 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/222 (0.5%)		1/232 (0.4%)
Respiratory failure	0/222 (0%)		1/232 (0.4%)
Skin and subcutaneous tissue disorders
Urticaria	0/222 (0%)		1/232 (0.4%)
Surgical and medical procedures
Malignant tumour excision	1/222 (0.5%)		0/232 (0%)
Vascular disorders
Deep vein thrombosis	1/222 (0.5%)		2/232 (0.9%)
Venous thrombosis limb	1/222 (0.5%)		0/232 (0%)
Other (Not Including Serious) Adverse Events
	Litx + Chemotherapy		Chemotherapy Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	201/222 (90.5%)		207/232 (89.2%)
Blood and lymphatic system disorders
Anaemia	34/222 (15.3%)		35/232 (15.1%)
Leukopenia	23/222 (10.4%)		21/232 (9.1%)
Neutropenia	48/222 (21.6%)		43/232 (18.5%)
Thrombocytopenia	12/222 (5.4%)		13/232 (5.6%)
Gastrointestinal disorders
Abdominal pain	39/222 (17.6%)		37/232 (15.9%)
Abdominal pain upper	8/222 (3.6%)		5/232 (2.2%)
Constipation	15/222 (6.8%)		13/232 (5.6%)
Diarrhoea	40/222 (18%)		46/232 (19.8%)
Dyspepsia	4/222 (1.8%)		6/232 (2.6%)
Nausea	69/222 (31.1%)		67/232 (28.9%)
Stomatitis	11/222 (5%)		7/232 (3%)
Vomiting	37/222 (16.7%)		40/232 (17.2%)
General disorders
Asthenia	33/222 (14.9%)		44/232 (19%)
Chest pain	3/222 (1.4%)		5/232 (2.2%)
Chills	3/222 (1.4%)		5/232 (2.2%)
Fatigue	47/222 (21.2%)		45/232 (19.4%)
Oedema peripheral	12/222 (5.4%)		14/232 (6%)
Pyrexia	48/222 (21.6%)		34/232 (14.7%)
Hepatobiliary disorders
Hyperbilirubinaemia	6/222 (2.7%)		3/232 (1.3%)
Infections and infestations
Urinary tract infection	8/222 (3.6%)		8/232 (3.4%)
Injury, poisoning and procedural complications
Procedural pain	112/222 (50.5%)		0/232 (0%)
Investigations
Alanine aminotransferase increased	3/222 (1.4%)		7/232 (3%)
Aspartate aminotransferase increased	4/222 (1.8%)		7/232 (3%)
Blood albumin decreased	7/222 (3.2%)		4/232 (1.7%)
Blood alkaline phosphatase increased	7/222 (3.2%)		3/232 (1.3%)
Blood pressure increased	7/222 (3.2%)		2/232 (0.9%)
Eastern cooperative oncology group performance status worsened	10/222 (4.5%)		7/232 (3%)
Gamma-glutamyltransferase increased	7/222 (3.2%)		5/232 (2.2%)
Red blood cell sedimentation rate increased	1/222 (0.5%)		5/232 (2.2%)
Weight decreased	13/222 (5.9%)		11/232 (4.7%)
Metabolism and nutrition disorders
Decreased appetite	24/222 (10.8%)		20/232 (8.6%)
Hyperglycaemia	3/222 (1.4%)		5/232 (2.2%)
Hypoalbuminaemia	3/222 (1.4%)		7/232 (3%)
Hypokalaemia	3/222 (1.4%)		6/232 (2.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/222 (3.2%)		1/232 (0.4%)
Back pain	23/222 (10.4%)		9/232 (3.9%)
Musculoskeletal chest pain	7/222 (3.2%)		5/232 (2.2%)
Musculoskeletal pain	6/222 (2.7%)		2/232 (0.9%)
Pain in extremity	4/222 (1.8%)		6/232 (2.6%)
Nervous system disorders
Dizziness	3/222 (1.4%)		7/232 (3%)
Headache	7/222 (3.2%)		6/232 (2.6%)
Neuropathy peripheral	10/222 (4.5%)		6/232 (2.6%)
Paraesthesia	11/222 (5%)		12/232 (5.2%)
Peripheral sensory neuropathy	10/222 (4.5%)		19/232 (8.2%)
Psychiatric disorders
Anxiety	5/222 (2.3%)		2/232 (0.9%)
Insomnia	8/222 (3.6%)		11/232 (4.7%)
Respiratory, thoracic and mediastinal disorders
Cough	13/222 (5.9%)		10/232 (4.3%)
Dyspnoea	3/222 (1.4%)		9/232 (3.9%)
Skin and subcutaneous tissue disorders
Alopecia	14/222 (6.3%)		11/232 (4.7%)
Surgical and medical procedures
Catheterisation venous	13/222 (5.9%)		12/232 (5.2%)
Vascular disorders
Hypertension	14/222 (6.3%)		5/232 (2.2%)
Hypotension	0/222 (0%)		8/232 (3.4%)
Phlebitis	5/222 (2.3%)		6/232 (2.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.