Real-world Study for Patients With Advanced Hepatobiliary Tumors

Quality of Life Clinical Trial

Official title:

Real-world Study for Targeted Therapy and Immunotherapy in Patients With Advanced Hepatobiliary Tumors: a Multi-centers, Open-assess Observational Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03892577
• Other study ID #: JS-1391
• Status: Recruiting
• Start date: July 1, 2017
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2023
• Source: Peking Union Medical College Hospital
• Contact: Xiaobo Yang
• Phone: 010-69156043
• Email: zhaoht[@]pumch.cn
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The investigators design a large sample size study in the real-world to explore whether targeted therapy and immunotherapy can improve the survival, quality of life and drug safety of patients with advanced hepatobiliary tumors, and analyze the correlation between genetic variation and the effectiveness of therapy.

Description:

This trial is a multicenter, non-random, open and observational real-world study. It is estimated that 2000 patients with advanced hepatobiliary tumors will be enrolled in about 20 research centers. And it is planned to complete the enrollment within 2 years and it is expected that all enrolled subjects will reach the observation end point in 5 years.

After primary screening of all the patients, the investigators will further collect next-generation sequence(NGS) data and immunohistochemical data from the subjects, and enroll patients with any type of the following three treatment program: 1. Monotherapy or combination therapy with the targeted drug related to genetic variation of the subject; 2. Treatment with pan-target anti-angiogenic drugs, such as sorafenib, regorafenib, lenvatinib, apatinib, etc; 3. Immunotherapy or immunotherapy combined with targeted therapy.

The investigators will collect subjects' data from assessment centers each month and the efficacy, quality of life, and safety of treatment will be evaluated.

This trial plans to conduct an interim analysis and final analysis after collecting 500 cases, 1000 cases, and 2000 subjects, 3000 subjects,and explore the clinical application value of targeted therapy and immunotherapy in advanced hepatobiliary tumors in real world.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3000
• Est. completion date: December 31, 2025
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Subjects must meet all of the following criteria:

1. =18 years old, gender is not limited, and life expectancy is at least 6 months.

2. Diagnosed as primary liver cancer or biliary malignant tumor by histopathology or confirmed by imaging as HCC (by the American Association for the Study of Liver Diseases or standard for the diagnosis and treatment of primary liver cancer 2017 in China).

3. The Barcelona staging classification: class B-C.

4. Child-Pugh classification: class A-B.

5. At least one measurable lesion (RECIST v1.1)

6. Unable to perform radical surgery or patient refuse surgery.

7. Subjects need palliative treatment, and have received or are undergoing any of the following three treatments:

• Monotherapy or combination therapy with targeted drug associated with genetic variation in the subject.

• Or, treat with pan-target anti-vascular drugs, such as sorafenib, regorafenib, lenvatinib, apatinib.

• Or, immunotherapy or immunotherapy combined with targeted therapy or (and) classical chemotherapy.

8. Subjects volunteer to participate in the study and sign informed consent.

Exclusion Criteria:

Patients with one or more of the following criteria should be excluded:

1. Patients with early hepatobiliary tumor.

2. The Barcelona staging classification: class A.

3. Child-Pugh classification: class C.

4. Radical surgical resection.

5. CT or MRI shows unclear tumor boundary or no measurable lesions (RECIST v1.1).

6. Drug abuse, or any medical, psychological, or social condition that may affect the study, patient compliance, or even compromise the safety of the patient.

7. Conduct other experimental drug treatments other than this test within 4 weeks before the start of the study; or participate in another clinical study that has an impact on the results of this study.

8. Mental or medical instability makes patients unable or unwilling to sign informed consent.

9. Patients after comprehensive assessment are considered by the investigators to be unsuitable for participating in the study.

Related Conditions & MeSH terms

• Disease Control Rate
• Duration of Response
• Five-year Survival Rate
• Objective Response Rate
• Overall Survival
• Progression-free Survival
• Quality of Life

Intervention

Drug:
• Precision oncology including targeted therapy and immunotherapy
Therapeutic regimens are based on the clinicopathological features, genomic alterations, advices from multidisciplinary tumor board and willings from patients.

Locations

Country	Name	City	State
China	Chinese Academy of Medical Sciences & Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital	OrigiMed

Country where clinical trial is conducted

China, 

References & Publications (26)

Chen B, Lei J, Zhao H, Dong J, Zeng Z, Li Y, Yu L, Zhou L, Jia A, Lu Y, Cheng J. Efficacy and Safety of TKI Plus PD-1 Inhibitors in Elderly uHCC Patients: A Retrospective Study. J Hepatocell Carcinoma. 2022 Nov 8;9:1171-1185. doi: 10.2147/JHC.S387254. eCo — View Citation

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Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. doi: 10.1016/S1470-2045(08)70285-7. Epub 2008 Dec 16. — View Citation

Drilon A, Wang L, Arcila ME, Balasubramanian S, Greenbowe JR, Ross JS, Stephens P, Lipson D, Miller VA, Kris MG, Ladanyi M, Rizvi NA. Broad, Hybrid Capture-Based Next-Generation Sequencing Identifies Actionable Genomic Alterations in Lung Adenocarcinomas Otherwise Negative for Such Alterations by Other Genomic Testing Approaches. Clin Cancer Res. 2015 Aug 15;21(16):3631-9. doi: 10.1158/1078-0432.CCR-14-2683. Epub 2015 Jan 7. — View Citation

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Li S, Mao M. Next generation sequencing reveals genetic landscape of hepatocellular carcinomas. Cancer Lett. 2013 Nov 1;340(2):247-53. doi: 10.1016/j.canlet.2012.09.027. Epub 2012 Oct 12. — View Citation

Lin J, Yang X, Long J, Zhao S, Mao J, Wang D, Bai Y, Bian J, Zhang L, Yang X, Wang A, Xie F, Shi W, Yang H, Pan J, Hu K, Guan M, Zhao L, Huo L, Mao Y, Sang X, Wang K, Zhao H. Pembrolizumab combined with lenvatinib as non-first-line therapy in patients wit — View Citation

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857. — View Citation

Mao J, Wang D, Long J, Yang X, Lin J, Song Y, Xie F, Xun Z, Wang Y, Wang Y, Li Y, Sun H, Xue J, Song Y, Zuo B, Zhang J, Bian J, Zhang T, Yang X, Zhang L, Sang X, Zhao H. Gut microbiome is associated with the clinical response to anti-PD-1 based immunother — View Citation

Millner LM, Strotman LN. The Future of Precision Medicine in Oncology. Clin Lab Med. 2016 Sep;36(3):557-73. doi: 10.1016/j.cll.2016.05.003. — View Citation

Moriguchi M, Umemura A, Itoh Y. Current status and future prospects of chemotherapy for advanced hepatocellular carcinoma. Clin J Gastroenterol. 2016 Aug;9(4):184-90. doi: 10.1007/s12328-016-0670-7. Epub 2016 Jul 11. — View Citation

Ning C, Zhang X, Yang X, Sang X, Zhao H, Wang H. Conversion therapy of stage IVb unresectable gallbladder carcinoma. Hepatobiliary Surg Nutr. 2022 Apr;11(2):335-337. doi: 10.21037/hbsn-22-78. No abstract available. — View Citation

Rodriguez R, Miller KM. Unravelling the genomic targets of small molecules using high-throughput sequencing. Nat Rev Genet. 2014 Dec;15(12):783-96. doi: 10.1038/nrg3796. Epub 2014 Oct 14. — View Citation

Schulze K, Nault JC, Villanueva A. Genetic profiling of hepatocellular carcinoma using next-generation sequencing. J Hepatol. 2016 Nov;65(5):1031-1042. doi: 10.1016/j.jhep.2016.05.035. Epub 2016 Jun 2. — View Citation

Sharma A, Dwary AD, Mohanti BK, Deo SV, Pal S, Sreenivas V, Raina V, Shukla NK, Thulkar S, Garg P, Chaudhary SP. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol. 2010 Oct 20;28(30):4581-6. doi: 10.1200/JCO.2010.29.3605. Epub 2010 Sep 20. — View Citation

Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721. — View Citation

Wang DX, Yang X, Lin JZ, Bai Y, Long JY, Yang XB, Seery S, Zhao HT. Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: A retrospective, real-world study conducted in China. World J Gastroenterol. 2020 Aug 14;26(30):4465 — View Citation

Wang YY, Yang X, Wang YC, Long JY, Sun HS, Li YR, Xun ZY, Zhang N, Xue JN, Ning C, Zhang JW, Zhu CP, Zhang LH, Yang XB, Zhao HT. Clinical outcomes of lenvatinib plus transarterial chemoembolization with or without programmed death receptor-1 inhibitors in — View Citation

Xie F, Chen B, Yang X, Wang H, Zhang G, Wang Y, Wang Y, Zhang N, Xue J, Long J, Li Y, Sun H, Xun Z, Liu K, Chen X, Song Y, Yang X, Lu Z, Mao Y, Sang X, Lu Y, Zhao H. Efficacy of immune checkpoint inhibitors plus molecular targeted agents after the progres — View Citation

Yang X, Chen B, Wang Y, Wang Y, Long J, Zhang N, Xue J, Xun Z, Zhang L, Cheng J, Lei J, Sun H, Li Y, Lin J, Xie F, Wang D, Pan J, Hu K, Guan M, Huo L, Shi J, Yu L, Zhou L, Zhou J, Lu Z, Yang X, Mao Y, Sang X, Lu Y, Zhao H. Real-world efficacy and prognost — View Citation

Yang X, Hu Y, Yang K, Wang D, Lin J, Long J, Xie F, Mao J, Bian J, Guan M, Pan J, Huo L, Hu K, Yang X, Mao Y, Sang X, Zhang J, Wang X, Zhang H, Zhao H. Cell-free DNA copy number variations predict efficacy of immune checkpoint inhibitor-based therapy in h — View Citation

Yang X, Xu H, Zuo B, Yang X, Bian J, Long J, Wang D, Zhang J, Ning C, Wang Y, Xun Z, Wang Y, Lu X, Mao Y, Sang X, Zhao H. Downstaging and resection of hepatocellular carcinoma in patients with extrahepatic metastases after stereotactic therapy. Hepatobili — View Citation

Zhu C, Xue J, Wang Y, Wang S, Zhang N, Wang Y, Zhang L, Yang X, Long J, Yang X, Sang X, Zhao H. Efficacy and safety of lenvatinib combined with PD-1/PD-L1 inhibitors plus Gemox chemotherapy in advanced biliary tract cancer. Front Immunol. 2023 Jan 18;14:1 — View Citation

Zuo B, Yang X, Yang X, Bian J, Long J, Wang D, Ning C, Wang Y, Xun Z, Wang Y, Lu X, Mao Y, Sang X, Zhao H. A real-world study of the efficacy and safety of anti-PD-1 antibodies plus lenvatinib in patients with advanced gallbladder cancer. Cancer Immunol I — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Time from the date of initial treatment to death for any cause.	two years
Primary	Progression-free Survival (PFS)	A duration from the date of initial treatment with apatinib to disease progression (as defined by RECIST) or death.	six months
Secondary	Objective Response Rate (ORR)	Percentage of subjects with complete response and partial response.	one year
Secondary	Disease Control Rate (DCR)	Percentage of subjects with complete remission, partial remission, or stable disease during treatment or within 30 days of termination of test drug.	six months
Secondary	Incidence of Treatment-Emergent Adverse Event	Percentage of subjects who develop any adverse events (CTCAE 4.0).	one year
Secondary	Quality of Life (QoL) after treatment	The life quality of every subject will be assessed every 3 months according to the 45-item FACT-Hep questionnaire, which assesses generic HRQL concerns and disease-specific issues.	one year