Radiotherapy/Apatinib for Adjuvant Treatment of HCC Patients receIved Curative reSEction With Microvascular Invasion (RAISE)

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ClinicalTrials.gov Identifier: NCT03732105

Recruitment Status : Not yet recruiting

First Posted : November 6, 2018

Last Update Posted : November 6, 2018

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Sponsor:

Information provided by (Responsible Party):

Ming Kuang, Sun Yat-sen University

Study Description

Brief Summary:

RAISE is a multicenter phase II randomized 2x2 factorial trial. The purpose is to further investigate both the efficacy and safety of the radiotherapy/apatinib for adjuvant treatment of HCC patients accepted radical resection with microvascular invasion.

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma Radiotherapy Apatinib Hepatectomy	Radiation: Radiotherapy Drug: Apatinib Drug: Radiotherapy+apatinib	Phase 2

Detailed Description:

RAISE trial will recruit 160 patients, and they will be randomized (1:1:1:1) to four groups (radiotherapy group, apatinib group, radiotherapy+apatinib group and control group). Patients in radiotherapy group will receive Intensity Modulated Radiation Therapy (IMRT) at a dose of 50Gy/25fraction after randomization. Patients in apatinib group will receive oral apatinib at an initial dose of 500mg/qd until recurrence, patient withdrawal or unacceptable toxic effects. Patients in radiotherapy+apatinib group will receive Intensity Modulated Radiation Therapy (IMRT) at a dose of 50Gy/25fraction after randomization and after radiotherapy they will receive oral apatinib at an initial dose of 500mg/qd until recurrence, patient withdrawal or unacceptable toxic effects. Patients on the control arm will be actively monitored after randomization.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	160 participants
Allocation:	Randomized
Intervention Model:	Factorial Assignment
Intervention Model Description:	2X2 factorial design
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Radiotherapy/Apatinib for Adjuvant Treatment of Hepatocellular Carcinoma Patients Accepted Curative Resection With Microvascular Invasion: a 2x2 Factorial Design Study
Estimated Study Start Date :	November 1, 2018
Estimated Primary Completion Date :	December 31, 2023
Estimated Study Completion Date :	December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Radiotherapy Patients in radiotherapy group will receive Intensity Modulated Radiation Therapy (IMRT) at a dose of 50Gy/25fraction after randomization. After radiotherapy, patients on the control arm will be actively monitored.	Radiation: Radiotherapy Patients in radiotherapy group will receive Intensity Modulated Radiation Therapy (IMRT) at a dose of 50Gy/25fraction after randomization. Other Name: RT
Experimental: Apatinib Patients in apatinib group will receive oral apatinib at an initial dose of 500mg daily until recurrence,death, patient withdrawal or unacceptable toxic effects.	Drug: Apatinib Patients in apatinib group will receive oral apatinib at an initial dose of 500mg daily until recurrence, death,patient withdrawal or unacceptable toxic effects. At the first occurrence of grade 3 or 4 toxicities, apatinib was delayed until recovery to grade 2 or below, and then treatment was resumed with a reduction to 500 mg and 250 mg taken on alternate days. At the second occurrence of grade 3 or 4 toxicities, apatinib was delayed until recovery to grade 2, and then treatment was resumed with a reduction to 250 mg once daily. Other Name: Anti-angiogenic therapy
Experimental: Radiotherapy and apatinib Patients in radiotherapy+apatinib group will receive Intensity Modulated Radiation Therapy (IMRT) at a dose of 50 Gy/25 fraction after randomization and after radiotherapy they will receive oral apatinib at an initial dose of 500mg/qd until recurrence,death,patient withdrawal or unacceptable toxic effects.	Drug: Radiotherapy+apatinib Patients in radiotherapy+apatinib group will receive Intensity Modulated Radiation Therapy (IMRT) at a dose of 50 Gy/25 fraction after randomization and after radiotherapy they will receive oral apatinib at an initial dose of 500mg daily until recurrence, death, patient withdrawal or unacceptable toxic effects. Two dose reductions were permitted for apatinib (500 mg and 250 mg taken on alternate days, and 250 mg once daily). At the first occurrence of grade 3 or 4 toxicities, apatinib was delayed until recovery to grade 2 or below, and then treatment was resumed with a reduction to 500 mg and 250 mg taken on alternate days. At the second occurrence of grade 3 or 4 toxicities, apatinib was delayed until recovery to grade 2, and then treatment was resumed with a reduction to 250 mg once daily. Other Name: RT+Anti-angiogenic therapy
No Intervention: Control group Patients on the control arm will be actively monitored after randomization.

Outcome Measures

Primary Outcome Measures :

Recurrence Free Survival,RFS [ Time Frame: two years ]
Defined in whole days as the time from randomisation until disease recurrence or death from any cause, whichever happens first.

Secondary Outcome Measures :

Time To Recurrence, TTR [ Time Frame: two years ]
Defined in whole days as the time from randomisation until disease recurrence.
Overall Survival, OS [ Time Frame: two years ]
Defined in whole days as the time from randomisation until death from any cause.
safety events [ Time Frame: two years ]
Safety events will be measured in terms of the occurrence, severity, type and causality of Adverse Events (AEs) during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 4).
health related quality of life [ Time Frame: two years ]
The quality of life is accessed by EORTC QLQ-C30 (version 3).

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Aged 18--75；
Primary treatment of HCC patients was treated with curative surgery. Postoperative pathology was diagnosed as hepatocellular carcinoma with microvascular invasion；
No residual and new lesions, no lymph node ,local and distant metastasis were detected after 4 weeks of postoperative ultrasound and enhanced CT/MRI.
ECOG 0/1 ;
Child-Pugh score 5-6;
A life expectancy of 6 months or more；
Adequate haematological, liver and renal function Neutrophil count ≥1.5 x 109/L; platelet count> 60 x 109/L; Haemoglobin concentration≥9.0 g/dL; Serum albumin≥ 3.0 g/dL; A total bilirubin of less than 1.5 times upper limit of normal; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 3 times upper limit of normal; Prothrombin time ≤3s above the control Serum creatinine concentration of 1.5 times the upper limit of the normal range or less; CCR ≥60ml/min
Written informed consent

Exclusion Criteria:

with tumor thrombus in the portal veins, hepatic veins, or bile ducts on preoperative radiological imaging
>3 tumor nodules in patients with multi-nodular HCC
have been treated with radiotherapy, TACE and ablation
subjects for pregnant or lactating women or family planning for two years
with HIV, HCV, syphilis infection;
with other malignant tumors or other malignant tumors within 5 years of entry;
organ transplant within 5 years of entry;
serious heart, kidney function and other serious organ dysfunction;
participated in clinical trials of other drugs within 12 months of entry

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03732105

Contacts

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Contact: Ming Kuang, PhD	008687755766 ext 8576	kuangm@mail.sysu.edu.cn

Locations

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China, Guangdong
The First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, China, 510080

Sponsors and Collaborators

Sun Yat-sen University

Investigators

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Study Chair:	Ming Kuang, PhD	First Affiliated Hospital, Sun Yat-Sen University

More Information

Publications of Results:

Rodríguez-Perálvarez M, Luong TV, Andreana L, Meyer T, Dhillon AP, Burroughs AK. A systematic review of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability. Ann Surg Oncol. 2013 Jan;20(1):325-39. doi: 10.1245/s10434-012-2513-1. Epub 2012 Nov 13. Review.

Wang WH, Wang Z, Wu JX, Zhang T, Rong WQ, Wang LM, Jin J, Wang SL, Song YW, Liu YP, Ren H, Fang H, Wang WQ, Liu XF, Yu ZH, Li YX. Survival benefit with IMRT following narrow-margin hepatectomy in patients with hepatocellular carcinoma close to major vessels. Liver Int. 2015 Dec;35(12):2603-10. doi: 10.1111/liv.12857. Epub 2015 Jun 3.

Yu W, Wang W, Rong W, Wang L, Xu Q, Wu F, Liu L, Wu J. Adjuvant radiotherapy in centrally located hepatocellular carcinomas after hepatectomy with narrow margin (<1 cm): a prospective randomized study. J Am Coll Surg. 2014 Mar;218(3):381-92. doi: 10.1016/j.jamcollsurg.2013.11.030. Epub 2013 Dec 2.

Lu W, Jin XL, Yang C, Du P, Jiang FQ, Ma JP, Yang J, Xie P, Zhang Z. Comparison of efficacy between TACE combined with apatinib and TACE alone in the treatment of intermediate and advanced hepatocellular carcinoma: A single-center randomized controlled trial. Cancer Biol Ther. 2017 Jun 3;18(6):433-438. doi: 10.1080/15384047.2017.1323589. Epub 2017 May 26.

Zhao F, Tian W, Zeng M, Xia J, Hu H, Hao X, Han L, Liu H, He Y, Zhu X, Liang L, Ao R, Wei M, Deng L, Wei Y. Apatinib alone or combined with radiotherapy in metastatic prostate cancer: Results from a pilot, multicenter study. Oncotarget. 2017 Nov 28;8(67):110774-110784. doi: 10.18632/oncotarget.22719. eCollection 2017 Dec 19.

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Responsible Party:	Ming Kuang, professor, Sun Yat-sen University
ClinicalTrials.gov Identifier:	NCT03732105
Other Study ID Numbers:	2018175
First Posted:	November 6, 2018 Key Record Dates
Last Update Posted:	November 6, 2018
Last Verified:	November 2018

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Additional relevant MeSH terms:

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Carcinoma Carcinoma, Hepatocellular Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Liver Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Liver Diseases	Apatinib Angiogenesis Inhibitors Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors

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