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

A Randomized, Double Blind, Placebo Controlled, Multicenter Phase III Study (AHELP) of Apatinib in Patients With Hepatocellular Carcinoma After Systemic Therapy（Chemotherapy and/or Targeted Therapy）

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02329860

Enrollment

400

Registered

2015-01-01

Start date

2014-03-26

Completion date

2019-08-14

Last updated

2024-01-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Carcinoma, Hepatocellular

Brief summary

This was a multicenter, randomized, double-blind, phase III trial. This clinical study evaluates the efficacy and safety of Apatinib in patients with advanced liver cancer who have progressed on Systemic Therapy (Chemotherapy and/or Targeted Therapy). Approximately 400 patients who meet the entry criteria will be randomly assigned in a 2:1 ratio to Apatinib or placebo (1/3 chance to receive placebo). Primary endpoint of the study is overall survival.

Interventions

DRUGApatinib

DRUGPlacebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. ≥ 18 years old. 2. Conform to the clinical diagnosis standard strictly or histological or cytological confirmation of HCC (hepatocellular carcinoma) who cannot benefit from treatments of established efficacy with higher priority such as resection, local ablation,and with at least one uni-dimensional measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST 1.1. 3. Failure or intolerance to prior treatment with chemotherapy and/or targeted therapy (Failure is defined as documented radiological progression according to the radiology charter. Intolerance is defined as ≥ grade 4 hematologic toxicities, ≥ grade 3 non-hematologic toxicities ≥ grade 2 heart, liver or kidney damage). 4. Systemic therapy must have been completed ≥2 weeks before randomization (AEs due to prior treatment ≤ grade 1). 5. Liver function status Child-Pugh Class A or B (score≤7). 6. Barcelona Clinic Liver Cancer stage Category B or C. 7. Eastern Cooperative Oncology Group Performance Status of 0 or 1 within 1 week before randomization. 8. Life expectancy of at least 12 weeks. 9. HBV DNA ≤ 2000IU/ml or 1×10E+4 copy/ml. 10. Adequate bone marrow, liver and renal function as assessed by the following laboratory tests conducted within 1 week before randomization. HB ≥ 90g/L; ANC≥1.5×10E+9/L; PLT≥80×10E+9/L; ALB ≥ 29g/L; ALT and AST \< 5×ULN; TBIL ≤1.5×ULN; Cr ≤1.5×ULN 11. Women of childbearing potential and men must agree to use adequate contraception .

Exclusion criteria

1. Any local treatment (included but not limited: resection, radiotherapy, TAE, TACE, TAI, RFA or PEI) within 4 weeks of randomization. 2. Known hepatic duct carcinoma, mixed cell carcinoma or fibrolamellar hepatocellular carcinoma, known history or suffering from other cancer(except of cured skin basal cell carcinoma or carcinoma in situ of cervix). 3. Patients who will receive liver transplantation. 4. Ascites with clinical symptoms, i.e. require Abdominal paracentesis or drainage treatment such as or Child-Pugh Score\>2. 5. Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg). 6. Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female≥ 470 ms). 7. Grade III-IV cardiac insufficiency, according to NYHA criteria or echocardiography check: LVEF\<50%. 8. Factors to affect oral administration（such as Patients unable to swallow oral medications, chronic diarrhea and ileus etc. situations evidently affect drug oral medication and absorption）. 9. Previous digestive tract bleeding history within 6 months or evident gastrointestinal bleeding tendency, such as,：Esophageal varices with bleeding risk, local active ulcerative lesions, fecal occult blood≥（++）；if fecal occult blood（+），gastroscope check is required. 10. The Within 28 days ahead of randomization, experience abdomen fistula, gastrointestinal perforation, or abdominal abscess 11. Coagulation abnormalities (INR \> 1.5 x ULN, or PT \> ULN +4 seconds), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy; 12. Occurrence of central nervous system metastatic or known brain metastatic; 13. Objective evidence of previous or current pulmonary fibrosis history, interstitial pneumonia, Pneumoconiosis, radiation pneumonitis, drug-related pneumonia, Pulmonary function damaged seriously etc. 14. Proteinuria ≥ (++) or 24 hours total urine protein \> 1.0 g. 15. Received powerful inhibitor of CYP3A4 within 7 days or powerful inducer of CYP3A4 within 12 days before randomization. 16. Pregnant or breast-feeding women; patients with fertility will not or there is no way to adopt effective contraceptive measures. 17. Mental disorders history, or Psychotropic drug abuse history. 18. Patients who has bone metastasis, has received Palliative radiotherapy (radiotherapy area \> 5% marrow area).

Design outcomes

Primary

Measure	Time frame
Overall Survival	Approximately 36 months

Secondary

Measure	Time frame
Time to Progression（TTP）	Approximately 36 months
Progression Free Survival (PFS)	Approximately 36 months
Objective Response Rate	Approximately 36 months
Disease Control Rate	Approximately 36 months

Countries

China

Participant flow

Participants by arm

Arm	Count
Apatinib 750 mg orally (p.o.) every day (qd), 28 days as one cycle Apatinib	261
Placebo orally (p.o.) every day (qd), 28 days as one cycle Placebo	132
Total	393

Baseline characteristics

Characteristic	Apatinib	Total	Placebo
Age, Continuous	50.8 years STANDARD_DEVIATION 10.7	50.7 years STANDARD_DEVIATION 10.7	50.3 years STANDARD_DEVIATION 10.9
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	261 Participants	393 Participants	132 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	0 Participants	0 Participants	0 Participants
Region of Enrollment China	261 participants	393 participants	132 participants
Sex: Female, Male Female	38 Participants	54 Participants	16 Participants
Sex: Female, Male Male	223 Participants	339 Participants	116 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	24 / 257	13 / 130
other Total, other adverse events	251 / 257	110 / 130
serious Total, serious adverse events	95 / 257	30 / 130