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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 4/2019

01-04-2019 | Hepatocellular Carcinoma | Review

Design and Endpoints of Clinical Trials, Current and Future

Author: Morris Sherman

Published in: Digestive Diseases and Sciences | Issue 4/2019

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Abstract

With the advent of several new systemic agents for the treatment of hepatocellular carcinoma and the prospect of more to come it is expected that many more clinical trials will be undertaken to establish the best treatment paradigm(s). In order to help develop the most efficient and most relevant clinical trials this review concentrates on endpoints that have been used in the past. Survival is the gold standard. None of the surrogate endpoints correspond completely with survival. In addition, alternative clinical trial designs are presented that may be more efficient than the usual phase I, II, and III clinical trial strategy that has been used in the past.
Literature
1.
Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–390.CrossRefPubMed
2.
Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;J389:56–66.CrossRef
3.
Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391:1163–1173.CrossRefPubMed
4.
Zhu, AX, Kang YK, Yen CJ, Finn RS, Galle PR, Llovet JM. REACH-2: a randomized, double-blind, placebo-controlled phase 3 study of ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated baseline alpha-fetoprotein (AFP) following first-line sorafenib. J Clin Oncol. 2018;36:4003.
5.
Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry A, Rimassa L, Ryoo BY. Cabozantinib versus placebo in patients) with advanced hepatocellular carcinoma who have received prior sorafenib: results from the randomized phase 3 CELESTIAL trial. J Clin Oncol. 2018;36:4019.
6.
Llovet JM, Decaens T, Raoul JL, et al. Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study. J Clin Oncol. 2013;31:3509–3516.CrossRefPubMed
7.
Zhu AX, Rosmorduc O, Evans TR, et al. SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2015;33:559–566.CrossRefPubMed
8.
Rimassa L, Assenat E, Peck-Radosavljevic M, et al. Tivantinib for second-line treatment of MET-high, advanced hepatocellular carcinoma (METIV-HCC): a final analysis of a phase 3, randomised, placebo-controlled study. Lancet Oncol. 2018;19:682–693.CrossRefPubMed
9.
Forner A, Ayuso C, Varela M, et al. Evaluation of tumor response after locoregional therapies in hepatocellular carcinoma: are response evaluation criteria in solid tumors reliable? Cancer. 2009;115:616–623.CrossRefPubMed
10.
Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52–60.CrossRefPubMed
11.
Weng Z, Ertle J, Zheng S, et al. Choi criteria are superior in evaluating tumor response in patients treated with transarterial radioembolization for hepatocellular carcinoma. Oncol Lett. 2013;6:1707–1712.CrossRefPubMedPubMedCentral
12.
Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001;35:421–430.CrossRefPubMed
13.
Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis. 2010;30:61–74.CrossRefPubMed
14.
Reig M, Rimola J, Torres F, et al. Postprogression survival of patients with advanced hepatocellular carcinoma: rationale for second-line trial design. Hepatology. 2013;58:2023–2031.CrossRefPubMed
15.
Llovet JM, Di Bisceglie AM, Bruix J, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008;100:698–711.CrossRefPubMed
16.
Khalaf N, Ying J, Mittal S, et al. Natural history of untreated hepatocellular carcinoma in a US cohort and the role of cancer surveillance. Clin Gastroenterol Hepatol. 2017;15:273–281.CrossRefPubMed
17.
Toyoda H, Lai PB, O’Beirne J, et al. Long-term impact of liver function on curative therapy for hepatocellular carcinoma: application of the ALBI grade. Br J Cancer. 2016;114:744–750.CrossRefPubMedPubMedCentral
18.
19.
Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol. 2004;130:417–422.PubMed
20.
21.
22.
Lopez-Chavez A, Thomas A, Rajan A, et al. Molecular profiling and targeted therapy for advanced thoracic malignancies: a biomarker-derived, multiarm, multihistology phase II basket trial. J Clin Oncol. 2015;33:1000–10077.CrossRefPubMedPubMedCentral
23.
Bretz F, Koenig F, Brannath W, Glimm E, Posch M. Tutorial in biostatistics: adaptive designs for confirmatory clinical trials. Stat Med. 2009;28:1181–1217.CrossRefPubMed
24.
Menis J, Hasan B, Besse B. New clinical research strategies in thoracic oncology: clinical trial design, adaptive, basket and umbrella trials, new end-points and new evaluations of response. Eur Respir Rev. 2014;23:367–378.CrossRefPubMed
Metadata
Title
Design and Endpoints of Clinical Trials, Current and Future
Author
Morris Sherman
Publication date
01-04-2019
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 4/2019
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-019-05541-6

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