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Study of Apatinib After Systemic Therapy in Patients With Hepatocellular Carcinoma(AHELP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT02329860

Recruitment Status : Completed

First Posted : January 1, 2015

Results First Posted : January 22, 2024

Last Update Posted : January 22, 2024

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborator:

NanJing PLA 81 Hospital

Information provided by (Responsible Party):

Jiangsu HengRui Medicine Co., Ltd.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Condition	Carcinoma, Hepatocellular
Interventions	Drug: Apatinib Drug: Placebo
Enrollment	400

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Apatinib	Placebo
Arm/Group Description	750 mg orally (p.o.) every day (qd)...	orally (p.o.) every day (qd), 28 da...
Arm/Group Description	750 mg orally (p.o.) every day (qd), 28 days as one cycle Apatinib	orally (p.o.) every day (qd), 28 days as one cycle Placebo
Period Title: Overall Study
Started	267	133
Treated	261	132
Completed	161	107
Not Completed	106	26

Baseline Characteristics

Arm/Group Title		Apatinib	Placebo	Total
Arm/Group Description		750 mg orally (p.o.) every day (qd)...	orally (p.o.) every day (qd), 28 da...	Total of all reporting groups
Arm/Group Description		750 mg orally (p.o.) every day (qd), 28 days as one cycle Apatinib	orally (p.o.) every day (qd), 28 days as one cycle Placebo	Total of all reporting groups
Overall Number of Baseline Participants		261	132	393
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	261 participants	132 participants	393 participants
		50.8 (10.7)	50.3 (10.9)	50.7 (10.7)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	261 participants	132 participants	393 participants
	Female	38 14.6%	16 12.1%	54 13.7%
	Male	223 85.4%	116 87.9%	339 86.3%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	261 participants	132 participants	393 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	261 100.0%	132 100.0%	393 100.0%
	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
China	Number Analyzed	261 participants	132 participants	393 participants
China		261	132	393

Outcome Measures

1.Primary Outcome


Title	Overall Survival
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Approximately 36 months

Outcome Measure Data

Analysis Population Description

The primary efficacy endpoint was analyzed in FAS.


Arm/Group Title	Apatinib	Placebo
Arm/Group Description:	750 mg orally (p.o.) every day (qd)...	orally (p.o.) every day (qd), 28 da...
Arm/Group Description:	750 mg orally (p.o.) every day (qd), 28 days as one cycle Apatinib	orally (p.o.) every day (qd), 28 days as one cycle Placebo
Overall Number of Participants Analyzed	261	132
Median (95% Confidence Interval) Unit of Measure: months
	8.7 (7.5 to 9.8)	6.8 (5.7 to 9.1)

2.Secondary Outcome


Title	Time to Progression（TTP）
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Approximately 36 months

Outcome Measure Data

Analysis Population Description

The secondary efficacy endpoint was analyzed in FAS.


Arm/Group Title	Apatinib	Placebo
Arm/Group Description:	750 mg orally (p.o.) every day (qd)...	orally (p.o.) every day (qd), 28 da...
Arm/Group Description:	750 mg orally (p.o.) every day (qd), 28 days as one cycle Apatinib	orally (p.o.) every day (qd), 28 days as one cycle Placebo
Overall Number of Participants Analyzed	261	132
Median (95% Confidence Interval) Unit of Measure: months
	4.7 (4.5 to 4.8)	1.9 (1.9 to 2.0)

3.Secondary Outcome


Title	Progression Free Survival (PFS)
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Approximately 36 months

Outcome Measure Data

Analysis Population Description

[The secondary efficacy endpoint was analyzed in FAS.


Arm/Group Title	Apatinib	Placebo
Arm/Group Description:	750 mg orally (p.o.) every day (qd)...	orally (p.o.) every day (qd), 28 da...
Arm/Group Description:	750 mg orally (p.o.) every day (qd), 28 days as one cycle Apatinib	orally (p.o.) every day (qd), 28 days as one cycle Placebo
Overall Number of Participants Analyzed	261	132
Median (95% Confidence Interval) Unit of Measure: months
	4.5 (3.9 to 4.7)	1.9 (1.9 to 2.0)

4.Secondary Outcome


Title	Objective Response Rate
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Approximately 36 months

Outcome Measure Data

Analysis Population Description

The secondary efficacy endpoint was analyzed in FAS


Arm/Group Title	Apatinib	Placebo
Arm/Group Description:	750 mg orally (p.o.) every day (qd)...	orally (p.o.) every day (qd), 28 da...
Arm/Group Description:	750 mg orally (p.o.) every day (qd), 28 days as one cycle Apatinib	orally (p.o.) every day (qd), 28 days as one cycle Placebo
Overall Number of Participants Analyzed	261	132
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	10.7 (7.2 to 15.1)	1.5 (0.2 to 5.4)

5.Secondary Outcome


Title	Disease Control Rate
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Approximately 36 months

Outcome Measure Data

Analysis Population Description

The secondary efficacy endpoint was analyzed in FAS.


Arm/Group Title	Apatinib	Placebo
Arm/Group Description:	750 mg orally (p.o.) every day (qd)...	orally (p.o.) every day (qd), 28 da...
Arm/Group Description:	750 mg orally (p.o.) every day (qd), 28 days as one cycle Apatinib	orally (p.o.) every day (qd), 28 days as one cycle Placebo
Overall Number of Participants Analyzed	261	132
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	61.3 (55.1 to 67.2)	28.8 (21.2 to 37.3)

Adverse Events

Time Frame	approximately 5 years
Adverse Event Reporting Description	Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.

Arm/Group Title	Apatinib	Placebo
Arm/Group Description	750 mg orally (p.o.) every day (qd)...	orally (p.o.) every day (qd), 28 da...
Arm/Group Description	750 mg orally (p.o.) every day (qd), 28 days as one cycle Apatinib	orally (p.o.) every day (qd), 28 days as one cycle Placebo
All-Cause Mortality
	Apatinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	24/257 (9.34%)	13/130 (10.00%)
Serious Adverse Events Serious Adverse Events
	Apatinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	95/257 (36.96%)	30/130 (23.08%)
Blood and lymphatic system disorders
Anaemia ^†	1/257 (0.39%)	1/130 (0.77%)
Febrile neutropenia ^†	1/257 (0.39%)	0/130 (0.00%)
Cardiac disorders
Acute coronary syndrome ^†	0/257 (0.00%)	1/130 (0.77%)
Palpitations ^†	1/257 (0.39%)	0/130 (0.00%)
Sinus bradycardia ^†	1/257 (0.39%)	0/130 (0.00%)
Gastrointestinal disorders
Upper gastrointestinal haemorrhage ^†	13/257 (5.06%)	1/130 (0.77%)
Gastrointestinal haemorrhage ^†	5/257 (1.95%)	0/130 (0.00%)
Diarrhoea ^†	3/257 (1.17%)	1/130 (0.77%)
Abdominal pain upper ^†	2/257 (0.78%)	0/130 (0.00%)
Melaena ^†	1/257 (0.39%)	1/130 (0.77%)
Vomiting ^†	2/257 (0.78%)	0/130 (0.00%)
Abdominal distension ^†	1/257 (0.39%)	0/130 (0.00%)
Duodenal ulcer ^†	1/257 (0.39%)	0/130 (0.00%)
Gastritis ^†	1/257 (0.39%)	0/130 (0.00%)
Intestinal obstruction ^†	1/257 (0.39%)	0/130 (0.00%)
Mouth ulceration ^†	1/257 (0.39%)	0/130 (0.00%)
Nausea ^†	1/257 (0.39%)	0/130 (0.00%)
General disorders
Death ^†	8/257 (3.11%)	9/130 (6.92%)
Multiple organ dysfunction syndrome ^†	3/257 (1.17%)	1/130 (0.77%)
Pyrexia ^†	2/257 (0.78%)	2/130 (1.54%)
Fatigue ^†	2/257 (0.78%)	0/130 (0.00%)
Asthenia ^†	1/257 (0.39%)	0/130 (0.00%)
Disease progression ^†	1/257 (0.39%)	0/130 (0.00%)
Hepatobiliary disorders
Hepatic function abnormal ^†	4/257 (1.56%)	1/130 (0.77%)
Hepatic failure ^†	1/257 (0.39%)	2/130 (1.54%)
Cholecystitis ^†	2/257 (0.78%)	0/130 (0.00%)
Perihepatic discomfort ^†	1/257 (0.39%)	1/130 (0.77%)
Hyperbilirubinaemia ^†	1/257 (0.39%)	0/130 (0.00%)
Infections and infestations
Lung infection ^†	8/257 (3.11%)	1/130 (0.77%)
Gastroenteritis ^†	2/257 (0.78%)	0/130 (0.00%)
Biliary tract infection ^†	1/257 (0.39%)	0/130 (0.00%)
Gingivitis ^†	1/257 (0.39%)	0/130 (0.00%)
Peritonitis ^†	1/257 (0.39%)	0/130 (0.00%)
Upper respiratory tract infection ^†	1/257 (0.39%)	0/130 (0.00%)
Injury, poisoning and procedural complications
Overdose ^†	7/257 (2.72%)	2/130 (1.54%)
Fibula fracture ^†	0/257 (0.00%)	1/130 (0.77%)
Post procedural bile leak ^†	0/257 (0.00%)	1/130 (0.77%)
Toxicity to various agents ^†	0/257 (0.00%)	1/130 (0.77%)
Investigations
Aspartate aminotransferase increased ^†	3/257 (1.17%)	0/130 (0.00%)
Blood bilirubin increased ^†	1/257 (0.39%)	1/130 (0.77%)
Bilirubin conjugated increased ^†	0/257 (0.00%)	1/130 (0.77%)
Blood phosphorus decreased ^†	1/257 (0.39%)	0/130 (0.00%)
Blood sodium decreased ^†	1/257 (0.39%)	0/130 (0.00%)
Platelet count decreased ^†	1/257 (0.39%)	0/130 (0.00%)
Metabolism and nutrition disorders
Hypoalbuminaemia ^†	2/257 (0.78%)	0/130 (0.00%)
Electrolyte imbalance ^†	1/257 (0.39%)	0/130 (0.00%)
Hypoglycaemia ^†	1/257 (0.39%)	0/130 (0.00%)
Hypokalaemia ^†	1/257 (0.39%)	0/130 (0.00%)
Hyponatraemia ^†	1/257 (0.39%)	0/130 (0.00%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain ^†	1/257 (0.39%)	1/130 (0.77%)
Back pain ^†	1/257 (0.39%)	0/130 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage ^†	1/257 (0.39%)	1/130 (0.77%)
Cancer pain ^†	1/257 (0.39%)	0/130 (0.00%)
Metastatic neoplasm ^†	0/257 (0.00%)	1/130 (0.77%)
Neoplasm progression ^†	1/257 (0.39%)	0/130 (0.00%)
Tumour rupture ^†	0/257 (0.00%)	1/130 (0.77%)
Nervous system disorders
Hepatic encephalopathy ^†	7/257 (2.72%)	1/130 (0.77%)
Cerebral haemorrhage ^†	2/257 (0.78%)	0/130 (0.00%)
Encephalopathy ^†	2/257 (0.78%)	0/130 (0.00%)
Headache ^†	2/257 (0.78%)	0/130 (0.00%)
Brain stem haemorrhage ^†	1/257 (0.39%)	0/130 (0.00%)
Dizziness ^†	1/257 (0.39%)	0/130 (0.00%)
Syncope ^†	1/257 (0.39%)	0/130 (0.00%)
Renal and urinary disorders
Haematuria ^†	4/257 (1.56%)	0/130 (0.00%)
Proteinuria ^†	3/257 (1.17%)	0/130 (0.00%)
Renal hydrocele ^†	1/257 (0.39%)	0/130 (0.00%)
Reproductive system and breast disorders
Acquired hydrocele ^†	1/257 (0.39%)	0/130 (0.00%)
Vaginal haemorrhage ^†	1/257 (0.39%)	0/130 (0.00%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis ^†	4/257 (1.56%)	1/130 (0.77%)
Pleural effusion ^†	2/257 (0.78%)	0/130 (0.00%)
Respiratory failure ^†	2/257 (0.78%)	0/130 (0.00%)
Bronchial haemorrhage ^†	0/257 (0.00%)	1/130 (0.77%)
Cough ^†	1/257 (0.39%)	0/130 (0.00%)
Dyspnoea ^†	0/257 (0.00%)	1/130 (0.77%)
Pneumonitis ^†	0/257 (0.00%)	1/130 (0.77%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome ^†	1/257 (0.39%)	0/130 (0.00%)
Vascular disorders
Hypertension ^†	2/257 (0.78%)	0/130 (0.00%)
Secondary hypertension ^†	1/257 (0.39%)	0/130 (0.00%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Apatinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	251/257 (97.67%)	110/130 (84.62%)
Blood and lymphatic system disorders
Anaemia ^†	30/257 (11.67%)	13/130 (10.00%)
Gastrointestinal disorders
Diarrhoea ^†	105/257 (40.86%)	21/130 (16.15%)
Vomiting ^†	70/257 (27.24%)	16/130 (12.31%)
Nausea ^†	60/257 (23.35%)	12/130 (9.23%)
Abdominal pain ^†	54/257 (21.01%)	16/130 (12.31%)
Abdominal pain upper ^†	49/257 (19.07%)	12/130 (9.23%)
Abdominal distension ^†	48/257 (18.68%)	19/130 (14.62%)
Mouth ulceration ^†	28/257 (10.89%)	1/130 (0.77%)
Constipation ^†	26/257 (10.12%)	4/130 (3.08%)
Stomatitis ^†	19/257 (7.39%)	3/130 (2.31%)
Gingival pain ^†	13/257 (5.06%)	1/130 (0.77%)
General disorders
Asthenia ^†	85/257 (33.07%)	23/130 (17.69%)
Pyrexia ^†	42/257 (16.34%)	9/130 (6.92%)
Oedema peripheral ^†	23/257 (8.95%)	9/130 (6.92%)
Fatigue ^†	22/257 (8.56%)	4/130 (3.08%)
Chest pain ^†	19/257 (7.39%)	2/130 (1.54%)
Infections and infestations
Upper respiratory tract infection ^†	23/257 (8.95%)	8/130 (6.15%)
Investigations
Platelet count decreased ^†	143/257 (55.64%)	23/130 (17.69%)
Aspartate aminotransferase increased ^†	136/257 (52.92%)	43/130 (33.08%)
Blood bilirubin increased ^†	133/257 (51.75%)	40/130 (30.77%)
White blood cell count decreased ^†	105/257 (40.86%)	10/130 (7.69%)
Neutrophil count decreased ^†	97/257 (37.74%)	10/130 (7.69%)
Alanine aminotransferase increased ^†	88/257 (34.24%)	28/130 (21.54%)
Bilirubin conjugated increased ^†	83/257 (32.30%)	18/130 (13.85%)
Gamma-glutamyltransferase increased ^†	53/257 (20.62%)	25/130 (19.23%)
Protein urine present ^†	53/257 (20.62%)	8/130 (6.15%)
Blood bilirubin unconjugated increased ^†	40/257 (15.56%)	6/130 (4.62%)
Blood pressure increased ^†	39/257 (15.18%)	5/130 (3.85%)
Blood lactate dehydrogenase increased ^†	33/257 (12.84%)	9/130 (6.92%)
Blood alkaline phosphatase increased ^†	30/257 (11.67%)	13/130 (10.00%)
Blood urine present ^†	27/257 (10.51%)	6/130 (4.62%)
Haemoglobin decreased ^†	21/257 (8.17%)	2/130 (1.54%)
Weight decreased ^†	21/257 (8.17%)	6/130 (4.62%)
Urobilinogen urine increased ^†	20/257 (7.78%)	7/130 (5.38%)
Blood albumin decreased ^†	19/257 (7.39%)	4/130 (3.08%)
Red blood cells urine positive ^†	19/257 (7.39%)	5/130 (3.85%)
White blood cells urine positive ^†	16/257 (6.23%)	5/130 (3.85%)
Urine bilirubin increased ^†	14/257 (5.45%)	4/130 (3.08%)
Protein total decreased ^†	13/257 (5.06%)	3/130 (2.31%)
Metabolism and nutrition disorders
Decreased appetite ^†	86/257 (33.46%)	13/130 (10.00%)
Hypoalbuminaemia ^†	47/257 (18.29%)	12/130 (9.23%)
Hypokalaemia ^†	28/257 (10.89%)	6/130 (4.62%)
Hyponatraemia ^†	25/257 (9.73%)	6/130 (4.62%)
Hypophosphataemia ^†	13/257 (5.06%)	4/130 (3.08%)
Musculoskeletal and connective tissue disorders
Back pain ^†	29/257 (11.28%)	9/130 (6.92%)
Pain in extremity ^†	27/257 (10.51%)	1/130 (0.77%)
Musculoskeletal pain ^†	24/257 (9.34%)	6/130 (4.62%)
Nervous system disorders
Headache ^†	74/257 (28.79%)	7/130 (5.38%)
Dizziness ^†	39/257 (15.18%)	4/130 (3.08%)
Psychiatric disorders
Insomnia ^†	17/257 (6.61%)	6/130 (4.62%)
Renal and urinary disorders
Proteinuria ^†	114/257 (44.36%)	26/130 (20.00%)
Respiratory, thoracic and mediastinal disorders
Cough ^†	43/257 (16.73%)	10/130 (7.69%)
Dysphonia ^†	28/257 (10.89%)	0/130 (0.00%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome ^†	144/257 (56.03%)	5/130 (3.85%)
Rash ^†	35/257 (13.62%)	6/130 (4.62%)
Vascular disorders
Hypertension ^†	123/257 (47.86%)	18/130 (13.85%)
† 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.

All clinical study findings and documents will be regarded as confidential. The investigator and members of his/her research team must not disclose such information without prior written approval from the sponsor.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Zexiang.huang/ project manager
Organization:	clinical operation
Phone:	13811725417
EMail:	zexiang.huang@hengrui.com

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

Qin S, Li Q, Gu S, Chen X, Lin L, Wang Z, Xu A, Chen X, Zhou C, Ren Z, Yang L, Xu L, Bai Y, Chen L, Li J, Pan H, Cao B, Fang W, Wu W, Wang G, Cheng Y, Yu Z, Zhu X, Jiang D, Lu Y, Wang H, Xu J, Bai L, Liu Y, Lin H, Wu C, Zhang Y, Yan P, Jin C, Zou J. Apatinib as second-line or later therapy in patients with advanced hepatocellular carcinoma (AHELP): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Jul;6(7):559-568. doi: 10.1016/S2468-1253(21)00109-6. Epub 2021 May 8.

Layout table for additonal information

Responsible Party:	Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier:	NCT02329860
Other Study ID Numbers:	APTN-III-HCC
First Submitted:	December 30, 2014
First Posted:	January 1, 2015
Results First Submitted:	April 26, 2023
Results First Posted:	January 22, 2024
Last Update Posted:	January 22, 2024