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

Primary Purpose

Hepatocellular Carcinoma, Radiotherapy, Apatinib

Status

Not yet recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Radiotherapy

Apatinib

Radiotherapy+apatinib

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

The First Affiliated Hospital of Sun Yat-sen University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

No Intervention

Arm Label

Radiotherapy

Apatinib

Radiotherapy and apatinib

Control group

Arm Description

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.

Patients in apatinib group will receive oral apatinib at an initial dose of 500mg daily until recurrence,death, patient withdrawal or unacceptable toxic effects.

Patients on the control arm will be actively monitored after randomization.

Outcomes

Primary Outcome Measures

Recurrence Free Survival,RFS

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

Defined in whole days as the time from randomisation until disease recurrence.

Overall Survival, OS

Defined in whole days as the time from randomisation until death from any cause.

safety events

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

The quality of life is accessed by EORTC QLQ-C30 (version 3).

Full Information

NCT ID

NCT03732105

First Posted

November 4, 2018

Last Updated

November 4, 2018

Sponsor

Sun Yat-sen University

1. Study Identification

Unique Protocol Identification Number

NCT03732105

Brief Title

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

Acronym

RAISE

Official Title

Radiotherapy/Apatinib for Adjuvant Treatment of Hepatocellular Carcinoma Patients Accepted Curative Resection With Microvascular Invasion: a 2x2 Factorial Design Study

Study Type

Interventional

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Not yet recruiting

Study Start Date

November 1, 2018 (Anticipated)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma, Radiotherapy, Apatinib, Hepatectomy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Factorial Assignment

Model Description

2X2 factorial design

Masking

None (Open Label)

Allocation

Randomized

Enrollment

160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Radiotherapy

Arm Type

Experimental

Arm Description

Arm Title

Apatinib

Arm Type

Experimental

Arm Description

Patients in apatinib group will receive oral apatinib at an initial dose of 500mg daily until recurrence,death, patient withdrawal or unacceptable toxic effects.

Arm Title

Radiotherapy and apatinib

Arm Type

Experimental

Arm Description

Arm Title

Control group

Arm Type

No Intervention

Arm Description

Patients on the control arm will be actively monitored after randomization.

Intervention Type

Radiation

Intervention Name(s)

Radiotherapy

Other Intervention Name(s)

Intervention Description

Patients in radiotherapy group will receive Intensity Modulated Radiation Therapy (IMRT) at a dose of 50Gy/25fraction after randomization.

Intervention Type

Drug

Intervention Name(s)

Apatinib

Other Intervention Name(s)

Anti-angiogenic therapy

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Radiotherapy+apatinib

Other Intervention Name(s)

RT+Anti-angiogenic therapy

Intervention Description

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.

Primary Outcome Measure Information:

Title

Recurrence Free Survival,RFS

Description

Defined in whole days as the time from randomisation until disease recurrence or death from any cause, whichever happens first.

Time Frame

two years

Secondary Outcome Measure Information:

Title

Time To Recurrence, TTR

Description

Defined in whole days as the time from randomisation until disease recurrence.

Time Frame

two years

Title

Overall Survival, OS

Description

Defined in whole days as the time from randomisation until death from any cause.

Time Frame

two years

Title

safety events

Description

Time Frame

two years

Title

health related quality of life

Description

The quality of life is accessed by EORTC QLQ-C30 (version 3).

Time Frame

two years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ming Kuang, PhD

Phone

008687755766

Ext

8576

kuangm@mail.sysu.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ming Kuang, PhD

Organizational Affiliation

First Affiliated Hospital, Sun Yat-Sen University

Official's Role

Study Chair

Facility Information:

Facility Name

The First Affiliated Hospital of Sun Yat-sen University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510080

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

23149850

Citation

Rodriguez-Peralvarez 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.

Results Reference

result

PubMed Identifier

25939444

Citation

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.

Results Reference

result

PubMed Identifier

24559953

Citation

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.

Results Reference

result

PubMed Identifier

28548587

Citation

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.

Results Reference

result

PubMed Identifier

29340015

Citation

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.

Results Reference

result

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

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