Orantinib In Combination With Transcatheter Arterial Chemoembolization In Patients With Unresectable Hepatocellular Carcinoma (ORIENTAL)

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ClinicalTrials.gov Identifier: NCT01465464

Recruitment Status : Terminated

First Posted : November 4, 2011

Results First Posted : August 7, 2019

Last Update Posted : August 7, 2019

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Sponsor:

Information provided by (Responsible Party):

Taiho Pharmaceutical Co., Ltd.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Hepatocellular Carcinoma
Interventions	Drug: Orantinib (TSU-68) Drug: Placebo
Enrollment	888

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Orantinib	Placebo
Arm/Group Description	Orantinib (TSU-68): 200 mg (1 table...	Placebo: 1 tablet was administered ...
Arm/Group Description	Orantinib (TSU-68): 200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening.	Placebo: 1 tablet was administered orally twice per day after meals, morning and evening.
Period Title: Overall Study
Started	444	444
Completed	0	0
Not Completed	444	444
Reason Not Completed
Adverse Event	96	49
Lack of Efficacy	139	190
Physician Decision	13	5
Protocol Violation	1	1
Withdrawal by Subject	46	30
Other	9	3
Ongoing treatment at cutoff date	140	166

Baseline Characteristics

Arm/Group Title		Orantinib	Placebo	Total
Arm/Group Description		Orantinib (TSU-68): 200 mg (1 table...	Placebo: 1 tablet was administered ...	Total of all reporting groups
Arm/Group Description		Orantinib (TSU-68): 200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening.	Placebo: 1 tablet was administered orally twice per day after meals, morning and evening.	Total of all reporting groups
Overall Number of Baseline Participants		444	444	888
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	444 participants	444 participants	888 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	189 42.6%	202 45.5%	391 44.0%
	>=65 years	255 57.4%	242 54.5%	497 56.0%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	444 participants	444 participants	888 participants
	Female	81 18.2%	80 18.0%	161 18.1%
	Male	363 81.8%	364 82.0%	727 81.9%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	444 participants	444 participants	888 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	444 100.0%	444 100.0%	888 100.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	0 0.0%	0 0.0%	0 0.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	444 participants	444 participants	888 participants
South Korea		170	170	340
Japan		219	213	432
Taiwan		55	61	116

Outcome Measures

1.Primary Outcome


Title	Overall Survival(OS)
Description	[Not Specified]
Description	[Not Specified]
Time Frame	The time from the date of enrollment to the date of death from any cause, assessed up to three years after randomizationof the last patient

Outcome Measure Data

Analysis Population Description

When approximately 50% of the targeted number of time to TACE discontinuation events were confirmed, interim analysis was performed by IDMC.

Because the Committee considered that significant results would no longer be obtained, the IDMC recommended to the Sponsor that the clinical trial would be discontinued, and the Sponsor stopped this trial.


Arm/Group Title	Orantinib	Placebo
Arm/Group Description:	Orantinib (TSU-68): 200 mg (1 table...	Placebo: 1 tablet was administered ...
Arm/Group Description:	Orantinib (TSU-68): 200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening.	Placebo: 1 tablet was administered orally twice per day after meals, morning and evening.
Overall Number of Participants Analyzed	168	163
Median (95% Confidence Interval) Unit of Measure: days
	946.0 (807.0 to 1050.0)	984.0 ^[1] (864.0 to NA)

[1]

The upper limit of median OS didn't reach.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.435
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.090
	Confidence Interval	(2-Sided) 95% 0.878 to 1.352
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Time to Transcatheter Arterial Chemoembolization (TACE) Failure
Description	Patients should not receive additional TACE therapy in this study afte...
Description	Patients should not receive additional TACE therapy in this study after meeting any of the following conditions, at the Investigator's discretion. The patient develops an intra-hepatic lesion that is uncontrolled by serial TACE Deterioration in arterial pathways to treat HCC that makes additional TACE impossible Severe vascular invasion occurs that makes additional TACE impossible Extra hepatic spread considered relevant to life expectancy that requires another treatment modality for HCC Liver function at grade Child-Pugh class C lasting for 28 days
Time Frame	The time from the date of enrollment to the date of event for TACE discontinuation, assessed up to three years after randomizationof the last patient

Outcome Measure Data

Analysis Population Description

When approximately 50% of the targeted number of time to TACE discontinuation events were confirmed, interim analysis was performed by IDMC.


Arm/Group Title	Orantinib	Placebo
Arm/Group Description:	Orantinib (TSU-68): 200 mg (1 table...	Placebo: 1 tablet was administered ...
Arm/Group Description:	Orantinib (TSU-68): 200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening.	Placebo: 1 tablet was administered orally twice per day after meals, morning and evening.
Overall Number of Participants Analyzed	174	206
Median (95% Confidence Interval) Unit of Measure: days
	728.0 (604.0 to 813.0)	602.0 (539.0 to 724.0)

Adverse Events

Time Frame	From the date of the first treatment to 30 days after the last treatment
Adverse Event Reporting Description	Main treatment discontinuation criteria The Investigator concludes that the patients should be treated with another treatment modality except TACE for HCC Patient has unacceptable/intolerable toxicities Patient can not take both enhanced CT and enhanced MRI of the abdomen any more Patient wishes to discontinue the treatment

Arm/Group Title	Orantinib	Placebo
Arm/Group Description	Orantinib (TSU-68): 200 mg (1 table...	Placebo: 1 tablet was administered ...
Arm/Group Description	Orantinib (TSU-68): 200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening.	Placebo: 1 tablet was administered orally twice per day after meals, morning and evening.
All-Cause Mortality
	Orantinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	33/444 (7.43%)	24/444 (5.41%)
Serious Adverse Events Serious Adverse Events
	Orantinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	200/444 (45.05%)	134/444 (30.18%)
Blood and lymphatic system disorders
Anaemia ^† 1	3/444 (0.68%)	0/444 (0.00%)
Disseminated intravascular coagulation ^† 1	2/444 (0.45%)	0/444 (0.00%)
Leukocytosis ^† 1	1/444 (0.23%)	0/444 (0.00%)
Idiopathic thrombocytopenic purpura ^† 1	0/444 (0.00%)	1/444 (0.23%)
Cardiac disorders
Acute pericarditis ^† 1	1/444 (0.23%)	0/444 (0.00%)
Angina pectoris ^† 1	1/444 (0.23%)	0/444 (0.00%)
Atrial thrombosis ^† 1	1/444 (0.23%)	0/444 (0.00%)
Cardiopulmonary arrest ^† 1	1/444 (0.23%)	0/444 (0.00%)
Heart failure ^† 1	1/444 (0.23%)	0/444 (0.00%)
Left ventricular dysfunction ^† 1	1/444 (0.23%)	0/444 (0.00%)
Myocardial infarction ^† 1	3/444 (0.68%)	0/444 (0.00%)
Paroxysmal supraventricular tachycardia ^† 1	1/444 (0.23%)	0/444 (0.00%)
Pericardial effusion ^† 1	1/444 (0.23%)	0/444 (0.00%)
Acute myocardial infarction ^† 1	0/444 (0.00%)	1/444 (0.23%)
Congenital, familial and genetic disorders
Hydrocele cord ^† 1	1/444 (0.23%)	0/444 (0.00%)
Endocrine disorders
Hypothyroidism ^† 1	0/444 (0.00%)	1/444 (0.23%)
Eye disorders
Cataract ^† 1	4/444 (0.90%)	3/444 (0.68%)
Cataract aggravated ^† 1	3/444 (0.68%)	1/444 (0.23%)
Diabetic retinopathy ^† 1	0/444 (0.00%)	1/444 (0.23%)
Retinal macroaneurysm ^† 1	0/444 (0.00%)	1/444 (0.23%)
Gastrointestinal disorders
Abdominal pain ^† 1	9/444 (2.03%)	7/444 (1.58%)
Acute pancreatitis ^† 1	1/444 (0.23%)	0/444 (0.00%)
Anal fistula ^† 1	1/444 (0.23%)	0/444 (0.00%)
Acute gastric ulcer with haemorrhage ^† 1	0/444 (0.00%)	1/444 (0.23%)
Ascites ^† 1	19/444 (4.28%)	11/444 (2.48%)
Colonic polyp ^† 1	1/444 (0.23%)	0/444 (0.00%)
Dental caries ^† 1	2/444 (0.45%)	0/444 (0.00%)
Diarrhea ^† 1	4/444 (0.90%)	2/444 (0.45%)
Duodenal ulcer ^† 1	2/444 (0.45%)	0/444 (0.00%)
Duodenal ulcer hemorrhage ^† 1	1/444 (0.23%)	1/444 (0.23%)
Epigastric pain ^† 1	1/444 (0.23%)	0/444 (0.00%)
Esophageal hemorrhage ^† 1	1/444 (0.23%)	0/444 (0.00%)
Esophageal varices hemorrhage ^† 1	6/444 (1.35%)	7/444 (1.58%)
Enterocolitis ^† 1	0/444 (0.00%)	1/444 (0.23%)
Gastric varices bleeding ^† 1	1/444 (0.23%)	0/444 (0.00%)
Gastric varices haemorrhage ^† 1	2/444 (0.45%)	7/444 (1.58%)
Gastroduodenal ulcer ^† 1	1/444 (0.23%)	1/444 (0.23%)
Gastroesophageal varices hemorrhage ^† 1	1/444 (0.23%)	0/444 (0.00%)
Gastric perforation ^† 1	0/444 (0.00%)	1/444 (0.23%)
Gastrointestinal hemorrhage ^† 1	0/444 (0.00%)	2/444 (0.45%)
Incarcerated inguinal hernia ^† 1	1/444 (0.23%)	0/444 (0.00%)
Inguinal hernia ^† 1	1/444 (0.23%)	2/444 (0.45%)
Irritable bowel syndrome ^† 1	1/444 (0.23%)	0/444 (0.00%)
Ischemia bowel ^† 1	1/444 (0.23%)	0/444 (0.00%)
Ischemic enterocolitis ^† 1	1/444 (0.23%)	0/444 (0.00%)
Large intestine polyp ^† 1	1/444 (0.23%)	0/444 (0.00%)
Melaena ^† 1	1/444 (0.23%)	0/444 (0.00%)
Hematemesis ^† 1	0/444 (0.00%)	1/444 (0.23%)
Intestinal obstruction ^† 1	0/444 (0.00%)	1/444 (0.23%)
Intra-abdominal haemorrhage ^† 1	0/444 (0.00%)	1/444 (0.23%)
Mallory-Weiss syndrome ^† 1	0/444 (0.00%)	1/444 (0.23%)
Mouth haemorrhage ^† 1	0/444 (0.00%)	1/444 (0.23%)
Nausea ^† 1	1/444 (0.23%)	0/444 (0.00%)
Oesophageal varices haemorrhage ^† 1	6/444 (1.35%)	7/444 (1.58%)
Pancreatitis ^† 1	2/444 (0.45%)	0/444 (0.00%)
Periodontal disease ^† 1	1/444 (0.23%)	0/444 (0.00%)
Right upper quadrant pain ^† 1	1/444 (0.23%)	1/444 (0.23%)
Ulcer duodenal haemorrhage ^† 1	1/444 (0.23%)	0/444 (0.00%)
Upper gastrointestinal hemorrhage ^† 1	1/444 (0.23%)	1/444 (0.23%)
Varices oesophageal ^† 1	1/444 (0.23%)	6/444 (1.35%)
Vomiting ^† 1	3/444 (0.68%)	0/444 (0.00%)
General disorders
Condition aggravated ^† 1	1/444 (0.23%)	0/444 (0.00%)
Disease progression ^† 1	2/444 (0.45%)	0/444 (0.00%)
Edema limbs ^† 1	2/444 (0.45%)	1/444 (0.23%)
Fever ^† 1	13/444 (2.93%)	11/444 (2.48%)
Gait disturbance ^† 1	1/444 (0.23%)	0/444 (0.00%)
Malaise ^† 1	3/444 (0.68%)	0/444 (0.00%)
Multi organ failure ^† 1	1/444 (0.23%)	0/444 (0.00%)
Pain ^† 1	1/444 (0.23%)	0/444 (0.00%)
Weakness generalised ^† 1	5/444 (1.13%)	0/444 (0.00%)
Fatigue ^† 1	0/444 (0.00%)	2/444 (0.45%)
Hepatobiliary disorders
Acute cholecystitis ^† 1	1/444 (0.23%)	0/444 (0.00%)
Acute hepatic failure ^† 1	2/444 (0.45%)	1/444 (0.23%)
Bile duct stenosis ^† 1	1/444 (0.23%)	5/444 (1.13%)
Biliary fistula ^† 1	1/444 (0.23%)	0/444 (0.00%)
Biloma ^† 1	5/444 (1.13%)	1/444 (0.23%)
Cholangitis ^† 1	5/444 (1.13%)	2/444 (0.45%)
Cholangitis acute ^† 1	1/444 (0.23%)	2/444 (0.45%)
Cholecystitis ^† 1	3/444 (0.68%)	4/444 (0.90%)
Dilatation intrahepatic duct acquired ^† 1	1/444 (0.23%)	0/444 (0.00%)
Gallbladder perforation ^† 1	0/444 (0.00%)	1/444 (0.23%)
Haemobilia ^† 1	0/444 (0.00%)	2/444 (0.45%)
Hepatic failure ^† 1	16/444 (3.60%)	11/444 (2.48%)
Hepatic function disorder ^† 1	11/444 (2.48%)	4/444 (0.90%)
Hepatic necrosis ^† 1	1/444 (0.23%)	1/444 (0.23%)
Hepatopathy ^† 1	0/444 (0.00%)	2/444 (0.45%)
Hyperbilirubinemia ^† 1	1/444 (0.23%)	2/444 (0.45%)
Jaundice ^† 1	1/444 (0.23%)	2/444 (0.45%)
Obstructive jaundice ^† 1	0/444 (0.00%)	1/444 (0.23%)
Portal vein thrombosis ^† 1	2/444 (0.45%)	2/444 (0.45%)
Hepatic vein thrombosis ^† 1	1/444 (0.23%)	0/444 (0.00%)
Hepatorenal syndrome ^† 1	6/444 (1.35%)	0/444 (0.00%)
Appendicitis perforated ^† 1	2/444 (0.45%)	1/444 (0.23%)
Bacteremia ^† 1	3/444 (0.68%)	3/444 (0.68%)
Immune system disorders
Contrast media allergy ^† 1	1/444 (0.23%)	0/444 (0.00%)
Infections and infestations
Acute bronchitis ^† 1	1/444 (0.23%)	0/444 (0.00%)
Acute gastroenteritis ^† 1	2/444 (0.45%)	0/444 (0.00%)
Acute pyelonephritis ^† 1	2/444 (0.45%)	0/444 (0.00%)
Biliary tract infection ^† 1	1/444 (0.23%)	3/444 (0.68%)
Bronchopneumonia ^† 1	1/444 (0.23%)	0/444 (0.00%)
Cellulitis of foot ^† 1	1/444 (0.23%)	0/444 (0.00%)
Cryptococcal pneumonitis ^† 1	1/444 (0.23%)	0/444 (0.00%)
Cystitis ^† 1	1/444 (0.23%)	0/444 (0.00%)
Enteritis infectious ^† 1	1/444 (0.23%)	0/444 (0.00%)
Hepatic infection bacterial ^† 1	1/444 (0.23%)	0/444 (0.00%)
Herpes zoster ^† 1	1/444 (0.23%)	2/444 (0.45%)
Infectious colitis ^† 1	1/444 (0.23%)	1/444 (0.23%)
Intra-abdominal infection ^† 1	3/444 (0.68%)	0/444 (0.00%)
Liver abscess ^† 1	34/444 (7.66%)	3/444 (0.68%)
Otitis media chronic ^† 1	1/444 (0.23%)	0/444 (0.00%)
Periodontal abscess ^† 1	2/444 (0.45%)	0/444 (0.00%)
Pneumonia ^† 1	5/444 (1.13%)	1/444 (0.23%)
Pulpitis ^† 1	1/444 (0.23%)	0/444 (0.00%)
Rectal abscess ^† 1	1/444 (0.23%)	0/444 (0.00%)
Sepsis ^† 1	6/444 (1.35%)	4/444 (0.90%)
Spontaneous bacterial peritonitis ^† 1	5/444 (1.13%)	0/444 (0.00%)
Tuberculous pleurisy ^† 1	1/444 (0.23%)	1/444 (0.23%)
UTI ^† 1	1/444 (0.23%)	0/444 (0.00%)
Upper respiratory infection ^† 1	1/444 (0.23%)	0/444 (0.00%)
Urinary tract infection ^† 1	1/444 (0.23%)	2/444 (0.45%)
Pyelonephritis ^† 1	0/444 (0.00%)	1/444 (0.23%)
Injury, poisoning and procedural complications
Compression fracture ^† 1	1/444 (0.23%)	0/444 (0.00%)
Fall ^† 1	1/444 (0.23%)	1/444 (0.23%)
Fracture of lateral malleolus, closed ^† 1	2/444 (0.45%)	3/444 (0.68%)
Humerus fracture ^† 1	1/444 (0.23%)	1/444 (0.23%)
Maternal exposure during pregnancy ^† 1	1/444 (0.23%)	0/444 (0.00%)
Nerve injury ^† 1	1/444 (0.23%)	0/444 (0.00%)
Operative haemorrhage ^† 1	1/444 (0.23%)	0/444 (0.00%)
Polytraumatism ^† 1	1/444 (0.23%)	0/444 (0.00%)
Post embolization syndrome ^† 1	1/444 (0.23%)	0/444 (0.00%)
Post procedural bile leak ^† 1	3/444 (0.68%)	0/444 (0.00%)
Ankle fracture ^† 1	0/444 (0.00%)	1/444 (0.23%)
Femoral neck fracture ^† 1	0/444 (0.00%)	2/444 (0.45%)
Traffic accident ^† 1	0/444 (0.00%)	1/444 (0.23%)
Investigations
ALT increased ^† 1	3/444 (0.68%)	1/444 (0.23%)
AST increased ^† 1	3/444 (0.68%)	1/444 (0.23%)
Blood bilirubin increased ^† 1	1/444 (0.23%)	2/444 (0.45%)
CRP increased ^† 1	2/444 (0.45%)	0/444 (0.00%)
Creatinine increased ^† 1	2/444 (0.45%)	1/444 (0.23%)
Elevated liver enzymes ^† 1	1/444 (0.23%)	0/444 (0.00%)
Liver biopsy ^† 1	1/444 (0.23%)	0/444 (0.00%)
Spleen scan abnormal ^† 1	1/444 (0.23%)	0/444 (0.00%)
Platelet count decreased ^† 1	0/444 (0.00%)	1/444 (0.23%)
WBC decreased ^† 1	0/444 (0.00%)	1/444 (0.23%)
Hypokalaemia ^† 1	2/444 (0.45%)	1/444 (0.23%)
Metabolism and nutrition disorders
Anorexia ^† 1	2/444 (0.45%)	1/444 (0.23%)
Diabetes mellitus aggravated ^† 1	1/444 (0.23%)	2/444 (0.45%)
Electrolyte imbalance ^† 1	1/444 (0.23%)	0/444 (0.00%)
Gout aggravated ^† 1	1/444 (0.23%)	0/444 (0.00%)
Hypercalcaemia ^† 1	1/444 (0.23%)	1/444 (0.23%)
Hyperglycemia ^† 1	1/444 (0.23%)	4/444 (0.90%)
Hyperkalemia ^† 1	2/444 (0.45%)	0/444 (0.00%)
Hypoglycaemia ^† 1	2/444 (0.45%)	0/444 (0.00%)
Inappetence ^† 1	2/444 (0.45%)	0/444 (0.00%)
Inappetence ^† 1	1/444 (0.23%)	1/444 (0.23%)
Tumor lysis syndrome ^† 1	1/444 (0.23%)	0/444 (0.00%)
Hyponatremia ^† 1	0/444 (0.00%)	2/444 (0.45%)
Musculoskeletal and connective tissue disorders
Arthritis ^† 1	2/444 (0.45%)	0/444 (0.00%)
Back pain ^† 1	2/444 (0.45%)	2/444 (0.45%)
Cervical disc herniation ^† 1	1/444 (0.23%)	0/444 (0.00%)
Pain in thigh ^† 1	1/444 (0.23%)	0/444 (0.00%)
Pseudogout ^† 1	1/444 (0.23%)	0/444 (0.00%)
Rhabdomyolysis ^† 1	1/444 (0.23%)	0/444 (0.00%)
Spinal column stenosis ^† 1	3/444 (0.68%)	1/444 (0.23%)
Wrist pain ^† 1	1/444 (0.23%)	0/444 (0.00%)
Avascular necrosis femoral head ^† 1	0/444 (0.00%)	1/444 (0.23%)
Spondylitis ^† 1	0/444 (0.00%)	1/444 (0.23%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma ^† 1	1/444 (0.23%)	0/444 (0.00%)
Bone metastases ^† 1	8/444 (1.80%)	3/444 (0.68%)
Brain metastases ^† 1	1/444 (0.23%)	0/444 (0.00%)
Cancer of descending colon ^† 1	1/444 (0.23%)	0/444 (0.00%)
Gastric cancer ^† 1	2/444 (0.45%)	2/444 (0.45%)
Hemangioma ^† 1	1/444 (0.23%)	0/444 (0.00%)
Hepatocellular carcinoma non-resectable ^† 1	1/444 (0.23%)	5/444 (1.13%)
Hepatoma recurrent ^† 1	1/444 (0.23%)	0/444 (0.00%)
Liver carcinoma ruptured ^† 1	2/444 (0.45%)	6/444 (1.35%)
Lung metastases ^† 1	2/444 (0.45%)	0/444 (0.00%)
Pancreatic carcinoma ^† 1	1/444 (0.23%)	0/444 (0.00%)
Spinal metastases ^† 1	1/444 (0.23%)	0/444 (0.00%)
Tumor necrosis ^† 1	2/444 (0.45%)	0/444 (0.00%)
Tumor rupture ^† 1	1/444 (0.23%)	0/444 (0.00%)
Adenocarcinoma of the gastrooesophageal junction ^† 1	0/444 (0.00%)	1/444 (0.23%)
Benign neoplasm of spinal cord ^† 1	0/444 (0.00%)	1/444 (0.23%)
Bladder cancer ^† 1	0/444 (0.00%)	4/444 (0.90%)
Cecal cancer ^† 1	0/444 (0.00%)	1/444 (0.23%)
Inverting papilloma of the nasal cavity ^† 1	0/444 (0.00%)	1/444 (0.23%)
Malignant neoplasm of cheek mucosa ^† 1	0/444 (0.00%)	2/444 (0.45%)
Oesophageal carcinoma ^† 1	0/444 (0.00%)	1/444 (0.23%)
Rectal cancer ^† 1	0/444 (0.00%)	1/444 (0.23%)
Schwannoma ^† 1	0/444 (0.00%)	1/444 (0.23%)
Tumour embolism ^† 1	0/444 (0.00%)	1/444 (0.23%)
Nervous system disorders
Cerebral infarction ^† 1	5/444 (1.13%)	5/444 (1.13%)
Hepatic encephalopathy ^† 1	12/444 (2.70%)	6/444 (1.35%)
Intracranial hemorrhage ^† 1	3/444 (0.68%)	1/444 (0.23%)
Numbness of lower extremities ^† 1	1/444 (0.23%)	0/444 (0.00%)
Spinal cord compression ^† 1	1/444 (0.23%)	0/444 (0.00%)
Syncope ^† 1	1/444 (0.23%)	0/444 (0.00%)
Dizziness ^† 1	0/444 (0.00%)	1/444 (0.23%)
Psychiatric disorders
Delirium ^† 1	1/444 (0.23%)	0/444 (0.00%)
Orientation disturbed ^† 1	1/444 (0.23%)	0/444 (0.00%)
Renal and urinary disorders
Acute kidney injury ^† 1	4/444 (0.90%)	3/444 (0.68%)
Renal failure ^† 1	4/444 (0.90%)	4/444 (0.90%)
Reproductive system and breast disorders
Benign prostatic hyperplasia ^† 1	0/444 (0.00%)	1/444 (0.23%)
Respiratory, thoracic and mediastinal disorders
Asphyxia ^† 1	1/444 (0.23%)	0/444 (0.00%)
Aspiration pneumonitis ^† 1	2/444 (0.45%)	0/444 (0.00%)
Bronchiectasis ^† 1	1/444 (0.23%)	0/444 (0.00%)
COPD exacerbation ^† 1	1/444 (0.23%)	0/444 (0.00%)
Chronic cough ^† 1	2/444 (0.45%)	1/444 (0.23%)
Dyspnea ^† 1	2/444 (0.45%)	0/444 (0.00%)
Pleural effusion ^† 1	7/444 (1.58%)	2/444 (0.45%)
Pneumonitis ^† 1	1/444 (0.23%)	0/444 (0.00%)
Pulmonary embolism ^† 1	1/444 (0.23%)	1/444 (0.23%)
Respiratory failure ^† 1	1/444 (0.23%)	0/444 (0.00%)
Shortness of breath ^† 1	1/444 (0.23%)	0/444 (0.00%)
Asthma ^† 1	0/444 (0.00%)	1/444 (0.23%)
Atelectasis ^† 1	0/444 (0.00%)	1/444 (0.23%)
Skin and subcutaneous tissue disorders
Eczema nummular ^† 1	1/444 (0.23%)	0/444 (0.00%)
Stevens-Johnson syndrome ^† 1	0/444 (0.00%)	1/444 (0.23%)
Surgical and medical procedures
Gastrooesophageal variceal haemorrhage prophylaxis ^† 1	3/444 (0.68%)	0/444 (0.00%)
Induced abortion ^† 1	1/444 (0.23%)	0/444 (0.00%)
Oesophageal variceal ligation ^† 1	3/444 (0.68%)	5/444 (1.13%)
Vascular disorders
Varicose vein ruptured ^† 1	1/444 (0.23%)	0/444 (0.00%)
Abdominal aortic aneurysm ^† 1	0/444 (0.00%)	1/444 (0.23%)
Arterial stenosis ^† 1	0/444 (0.00%)	1/444 (0.23%)
Deep vein thrombosis ^† 1	0/444 (0.00%)	1/444 (0.23%)
Obstructive arteriosclerosis of lower extremities ^† 1	0/444 (0.00%)	1/444 (0.23%)
Vascular disorder ^† 1	0/444 (0.00%)	1/444 (0.23%)
1 Term from vocabulary, CTCAE, version 4.02 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Orantinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	443/444 (99.77%)	436/444 (98.20%)
Blood and lymphatic system disorders
Anaemia ^† 1	54/444 (12.16%)	32/444 (7.21%)
Gastrointestinal disorders
Abdominal distension ^† 1	50/444 (11.26%)	53/444 (11.94%)
Abdominal pain ^† 1	317/444 (71.40%)	292/444 (65.77%)
Abdominal pain upper ^† 1	56/444 (12.61%)	46/444 (10.36%)
Ascites ^† 1	140/444 (31.53%)	73/444 (16.44%)
Constipation ^† 1	179/444 (40.32%)	147/444 (33.11%)
Diarrhoea ^† 1	123/444 (27.70%)	70/444 (15.77%)
Dyspepsia ^† 1	51/444 (11.49%)	47/444 (10.59%)
Gastritis ^† 1	23/444 (5.18%)	29/444 (6.53%)
Gastrointestinal pain ^† 1	22/444 (4.95%)	14/444 (3.15%)
Nausea ^† 1	179/444 (40.32%)	179/444 (40.32%)
Vomiting ^† 1	126/444 (28.38%)	116/444 (26.13%)
General disorders
Chills ^† 1	34/444 (7.66%)	23/444 (5.18%)
Face oedema ^† 1	138/444 (31.08%)	8/444 (1.80%)
Fatigue ^† 1	101/444 (22.75%)	92/444 (20.72%)
Malaise ^† 1	101/444 (22.75%)	86/444 (19.37%)
Non-cardiac chest pain ^† 1	32/444 (7.21%)	25/444 (5.63%)
Oedema peripheral ^† 1	130/444 (29.28%)	59/444 (13.29%)
Pyrexia ^† 1	264/444 (59.46%)	284/444 (63.96%)
Hepatobiliary disorders
Hepatic failure ^† 1	24/444 (5.41%)	20/444 (4.50%)
Infections and infestations
Liver abscess ^† 1	30/444 (6.76%)	3/444 (0.68%)
Upper respiratory tract infection ^† 1	86/444 (19.37%)	85/444 (19.14%)
Investigations
ALT increased ^† 1	200/444 (45.05%)	170/444 (38.29%)
AST increased ^† 1	223/444 (50.23%)	189/444 (42.57%)
ALP increased ^† 1	64/444 (14.41%)	22/444 (4.95%)
Bilirubin increased ^† 1	77/444 (17.34%)	75/444 (16.89%)
CRP increased ^† 1	47/444 (10.59%)	44/444 (9.91%)
Lymphocyte count decreased ^† 1	40/444 (9.01%)	45/444 (10.14%)
Platelet count decreased ^† 1	53/444 (11.94%)	48/444 (10.81%)
Weight decreased ^† 1	31/444 (6.98%)	20/444 (4.50%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	209/444 (47.07%)	149/444 (33.56%)
Hyperkalaemia ^† 1	23/444 (5.18%)	14/444 (3.15%)
Hypoalbuminaemia ^† 1	98/444 (22.07%)	85/444 (19.14%)
Hypokalaemia ^† 1	34/444 (7.66%)	16/444 (3.60%)
Hyponatraemia ^† 1	31/444 (6.98%)	22/444 (4.95%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	34/444 (7.66%)	19/444 (4.28%)
Back pain ^† 1	90/444 (20.27%)	94/444 (21.17%)
Musculoskeletal pain ^† 1	38/444 (8.56%)	36/444 (8.11%)
Myalgia ^† 1	32/444 (7.21%)	22/444 (4.95%)
Pain in extremity ^† 1	40/444 (9.01%)	30/444 (6.76%)
Nervous system disorders
Dizziness ^† 1	38/444 (8.56%)	35/444 (7.88%)
Headache ^† 1	74/444 (16.67%)	62/444 (13.96%)
Psychiatric disorders
Insomnia ^† 1	79/444 (17.79%)	68/444 (15.32%)
Renal and urinary disorders
Chromaturia ^† 1	103/444 (23.20%)	18/444 (4.05%)
Proteinuria ^† 1	47/444 (10.59%)	17/444 (3.83%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	69/444 (15.54%)	68/444 (15.32%)
Dyspnoea ^† 1	29/444 (6.53%)	30/444 (6.76%)
Pleural effusion ^† 1	36/444 (8.11%)	16/444 (3.60%)
Skin and subcutaneous tissue disorders
Pruritus ^† 1	43/444 (9.68%)	51/444 (11.49%)
Vascular disorders
Hypertension ^† 1	59/444 (13.29%)	57/444 (12.84%)
1 Term from vocabulary, CTCAE, version 4.02 † 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 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

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Name/Title:	Taiho Pharmaceutical Co., Ltd.
Organization:	Clinical Trial Registration Contact
EMail:	toiawase@taiho.co.jp

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

Kudo M, Cheng AL, Park JW, Park JH, Liang PC, Hidaka H, Izumi N, Heo J, Lee YJ, Sheen IS, Chiu CF, Arioka H, Morita S, Arai Y. Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Lancet Gastroenterol Hepatol. 2018 Jan;3(1):37-46. doi: 10.1016/S2468-1253(17)30290-X. Epub 2017 Oct 4.

Layout table for additonal information

Responsible Party:	Taiho Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier:	NCT01465464
Other Study ID Numbers:	Taiho132150
First Submitted:	November 1, 2011
First Posted:	November 4, 2011
Results First Submitted:	November 4, 2018
Results First Posted:	August 7, 2019
Last Update Posted:	August 7, 2019

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