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

NCT02329860 | Completed Phase 3 Results

• 1 other identifier: APTN-III-HCC
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

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.

Conditions

Carcinoma, Hepatocellular

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Approximately 36 months

Secondary Outcomes (4)

• 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

Study Arms (2)

Apatinib

EXPERIMENTAL

750 mg orally (p.o.) every day (qd), 28 days as one cycle

Drug: Apatinib

Placebo

PLACEBO COMPARATOR

orally (p.o.) every day (qd), 28 days as one cycle

Drug: Placebo

Interventions

Apatinib DRUG

Apatinib

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years old.
• 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.
• 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).
• Systemic therapy must have been completed ≥2 weeks before randomization (AEs due to prior treatment ≤ grade 1).
• Liver function status Child-Pugh Class A or B (score≤7).
• Barcelona Clinic Liver Cancer stage Category B or C.
• Eastern Cooperative Oncology Group Performance Status of 0 or 1 within 1 week before randomization.
• Life expectancy of at least 12 weeks.
• HBV DNA ≤ 2000IU/ml or 1×10E+4 copy/ml.
• 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
• Women of childbearing potential and men must agree to use adequate contraception .

You may not qualify if:

• Any local treatment (included but not limited: resection, radiotherapy, TAE, TACE, TAI, RFA or PEI) within 4 weeks of randomization.
• 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).
• Patients who will receive liver transplantation.
• Ascites with clinical symptoms, i.e. require Abdominal paracentesis or drainage treatment such as or Child-Pugh Score\>2.
• 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).
• Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female≥ 470 ms).
• Grade III-IV cardiac insufficiency, according to NYHA criteria or echocardiography check: LVEF\<50%.
• 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）.
• 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.
• The Within 28 days ahead of randomization, experience abdomen fistula, gastrointestinal perforation, or abdominal abscess
• Coagulation abnormalities (INR \> 1.5 x ULN, or PT \> ULN +4 seconds), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy;
• Occurrence of central nervous system metastatic or known brain metastatic;
• Objective evidence of previous or current pulmonary fibrosis history, interstitial pneumonia, Pneumoconiosis, radiation pneumonitis, drug-related pneumonia, Pulmonary function damaged seriously etc.
• Proteinuria ≥ (++) or 24 hours total urine protein \> 1.0 g.
• Received powerful inhibitor of CYP3A4 within 7 days or powerful inducer of CYP3A4 within 12 days before randomization.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead
• NanJing PLA 81 Hospital: collaborator

Study Sites (1)

Jiangsu hengrui medicine CO. LTD

Lianyungang, Jiangsu, 222047, China

Location

Related Publications (1)

• 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.

  PMID: 33971141 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

apatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Results Point of Contact

• Title: Zexiang.huang/ project manager
• Organization: clinical operation

zexiang.huang@hengrui.com

13811725417

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2014
• First Posted: January 1, 2015
• Study Start: March 26, 2014
• Primary Completion: December 15, 2017
• Study Completion: August 14, 2019
• Last Updated: January 22, 2024
• Results First Posted: January 22, 2024

Record last verified: 2017-07

Locations

CN (1)