Phase II clinical trials in oncology: Are we hitting the target?

Expert Review of Anticancer Therapy

Volumn 10, Issue 3, 2010, Pages 427-438

  Ang, Mei Kim ^a   Tan, Say Beng ^b   Lim, Wan Teck ^a  

^a DIVISION OF MEDICAL ONCOLOGY   (Singapore)

^b SINGAPORE CLINICAL RESEARCH INSTITUTE   (Singapore)

Author keywords

Biomarker; Cytostatic agent; End point; Enrichment; Phase II study; Randomization; Targeted therapy

Indexed keywords

ANGIOGENESIS INHIBITOR; BIOLOGICAL MARKER; CARBOXYAMINOIMIDAZOLE; CYTARABINE; CYTOSTATIC AGENT; ERLOTINIB; FLUORODEOXYGLUCOSE F 18; GEMCITABINE; IDARUBICIN; IMATINIB; IMIDAZOLE DERIVATIVE; NUCLEAR MAGNETIC RESONANCE IMAGING AGENT; SORAFENIB; SUNITINIB; TRASTUZUMAB; TROXACITABINE; UNCLASSIFIED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; BAYES THEOREM; BREAST METASTASIS; CANCER CHEMOTHERAPY; CANCER SURVIVAL; CLINICAL TRIAL; COLORECTAL CARCINOMA; DIAGNOSTIC IMAGING; DRUG EFFICACY; DRUG MECHANISM; DRUG RESEARCH; DRUG RESPONSE; DRUG TARGETING; FREQUENCY ANALYSIS; GASTROINTESTINAL STROMAL TUMOR; GENE TARGETING; HUMAN; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; METHODOLOGY; NUCLEAR MAGNETIC RESONANCE IMAGING; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PANCREAS CANCER; PHARMACOGENETICS; PHASE 2 CLINICAL TRIAL; POSITRON EMISSION TOMOGRAPHY; PROGRESSION FREE SURVIVAL; PROTEIN TARGETING; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; REVIEW; TUMOR REGRESSION; TUMOR VOLUME;

ANTINEOPLASTIC AGENTS; BAYES THEOREM; CLINICAL TRIALS, PHASE II AS TOPIC; DRUG DELIVERY SYSTEMS; ENDPOINT DETERMINATION; HUMANS; NEOPLASMS; RESEARCH DESIGN; TUMOR MARKERS, BIOLOGICAL;

EID: 77949477559     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/ERA.09.178     Document Type: Review

References (78)

1. Chan JK, Ueda SM, Sugiyama VE et al. Analysis of Phase II studies on targeted agents and subsequent Phase III trials: what are the predictors for success? J. Clin. Oncol. 26(9), 1511-1518 (2008).
2. Cannistra SA. Phase II trials in Journal of Clinical Oncology. J. Clin. Oncol. 27(19), 3073-3076 (2009).
3. Gehan EA. The determination of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. J. Chron. Dis. 13, 346-353 (1961).
4. Simon R. Optimal two-stage designs for Phase II clinical trials. Control Clin. Trials 10(1), 1-10 (1989).
5. Korn EL, Arbuck SG, Pluda JM, Simon R, Kaplan RS, Christian MC. Clinical trial designs for cytostatic agents: are new approaches needed? J. Clin. Oncol. 19(1), 265-272 (2001).
6. Therasse P, Arbuck SG, Eisenhauer EA et al. New guidelines to evaluate the response to treatment in solid tumours. J. Natl Cancer Inst. 92(3), 205-216 (2000).
7. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 47(1), 201-214 (1981).
8. Ratain MJ, Eisen T, Stadler WM et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 24(16), 2505-2512 (2006).
9. Abou-Alfa GK, Schwartz L, Ricci S et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J. Clin. Oncol. 24(26), 4293-4300 (2006).
10. Escudier B, Eisen T, Stadler WM et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med. 356(2), 125-134 (2007).
11. Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359(4), 123-132 (2008).
12. Demetri GD, Van Oosterom A, Garrett CR et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumours after failure of imatinib: a randomised controlled trial. Lancet 368(9544), 1329-1338 (2006).
13. Shepherd FA, Rodrigues Pereira J et al. National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small cell lung cancer. N. Engl. J. Med. 353(2), 123-132 (2005).
14. Burris HA, Moore MJ, Andersen J et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J. Clin. Oncol. 15(6), 2403-2413 (1997)
15. Grothey A, Hedrick EE, Mass RD et al. Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF 2107. J. Clin. Oncol. 26(2), 183-189 (2008).
16. Goffin J, Baral S, Tu D, Nomikos D, Seymour L. Objective responses in patients with malignant melanoma or renal cell cancer in early clinical studies do not predict regulatory approval. Clin. Cancer Res. 11(16), 5928-5934 (2005).
17. Burzykowski T, Buyse M, Piccart-Gebhart MJ et al. Evaluation of tumor response, disease control, progression-free survival and time to progression as potential surrogate end points in metastatic breast cancer. J. Clin. Oncol. 26(12), 1987-1992 (2008).
18. El-Maraghi RH, Eisenhauer EA. Review of Phase II trial designs used in studies of molecular targeted agents: outcomes and predictors of success in Phase III. J. Clin. Oncol. 26(8), 1346-1354 (2008).
19. Sposto R, Gaynon PS. An adjustment for patient heterogeneity in the design of two-stage Phase II trials. Stat. Med. 28(20), 2566-2579 (2009).
20. Karrison TG, Maitland ML, Stadler WM, Ratain MJ. Design of Phase II clinical trials using a continuous endpoint of change in tumour size: application to a study of sorafenib and erlotinib in non small-cell lung cancer. J. Natl Cancer Inst. 99(19), 1455-1461 (2007)
21. Llovet JM, Di Bisceglie AM, Bruix J et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J. Natl Cancer Inst. 100(10), 698-711 (2008).
22. Benjamin RS, Choi H, Macapinlac HA et al. We should resist using RECIST, at least in GIST. J. Clin. Oncol. 25(13), 1760-1761 (2007).
23. Van Glabbeke M, Verweij J, Judson I et al. Progression-free rate as the principal end-point for Phase II trials in soft-tissue sarcomas. Eur. J. Cancer. 38(4), 543-549 (2002).
24. Le Cesne A, Van Glabbeke M, Verweij J et al. Absence of progression as assessed by response evaluation criteria in solid tumors predicts survival in advanced GI stromal tumors treated with imatinib mesylate: the Intergroup EORTC-ISG-AGITG Phase III Trial. J. Clin. Oncol. 27(24), 3969-3974 (2009).
25. Ballman KV, Buckner JC, Brown PD et al. The relationship between six-month progression-free survival and 12-month overall survival end points for Phase II trials in patients with glioblastoma multiforme. Neuro. Oncol. 9(1), 29-38 (2007).
26. Francart J, Legrand C, Sylvester R et al. Progression-free survival rate as primary end point for Phase II cancer clinical trials: application to mesothelioma - the EORTC Lung Cancer Group. J. Clin. Oncol. 24(19), 3007-3012 (2006).
27. Korn El, Liu PY, Lee SJ et al. Meta-analysis of Phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future Phase II trials. J. Clin. Oncol. 26(4), 527-534 (2008).
28. Sleijfer S, Ray-Coquard I, Papai Z et al. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a Phase II study from the European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC Study 62043). J. Clin. Oncol. 27(19), 3126-3132 (2009).
29. Mick R, Crowley JJ, Carroll RJ. Phase II clinical trial design for noncytotoxic anticancer agents for which time to disease progression is the primary endpoint. Cont. Clin. Trials 21(4), 343-359 (2000).
30. Choi H, Charnsangavej C, Faria SC et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J. Clin. Oncol. 25(13), 1753-1759 (2007).
31. Bryant J, Day R. Incorporating toxicity considerations into the design of two-stage Phase II clinical trials. Biometrics 51(4), 1372-1383 (1995).
32. Zee B, Melnychuk D, Dancey J et al. Multinomial Phase II cancer trials incorporating response and early progression. J. Biopharm. Stat. 9(2), 351-363 (1999).
33. Dent S, Zee B, Dancey J, Hanauske A, Wanders J, Eisenhauer E. Application of a new multinomial Phase II stopping rule using response and early progression. J. Clin. Oncol. 19(3), 785-791 (2001).
34. Goffin JR, Tu D. Phase II stopping rules that employ response rates and early progression. J. Clin. Oncol. 26(22), 3715-3720 (2008).
35. Rubinstein L, Crowley J, LeBlanc M, Sargent D. Randomized Phase II designs. Clin. Cancer Res. 15(6), 1883-1890 (2009).
36. Ratain MJ, Sargent DJ. Optimising the design of Phase II oncology trials: the importance of randomization. Eur. J. Cancer 45(2), 275-280 (2009).
37. Simon R, Wittes RE, Ellenberg SS. Randomized Phase II clinical trials. Cancer Treat. Rep. 69(12), 1375-1381 (1985).
38. Liu PY, Dahlberg S, Crowley J. Selection designs for pilot studies based on survival. Biometrics 49(2), 391-398 (1993).
39. Liu PY, Moon J, LeBlanc M. Phase II selection designs. In: Handbook of Statistics in Clinical Oncology (second edition). Crowley J, Ankerst DP (Ed.). Chapman and Hall/CRC, FL, USA 155-164 (2006).
40. Liu PY, LeBlanc M, Desai M. False positive rates of randomised Phase II designs. Cont. Clin. Trials 20(4), 343-352 (1999).
41. Rubinstein LV, Korn El, Freidlin B, Hunsberger S, Ivy SP, Smith NA. Design issues of randomized Phase II trials and a proposal for Phase II screening trials. J. Clin. Oncol. 23(28), 7199-7206 (2005).
42. Kopec JA, Abrahamowicz M, Esdaile JM. Randomized discontinuation trials: utility and efficiency. J. Clin. Epidemiol. 46(9), 959-971 (1993).
43. Rosner GL, Stadler W, Ratain MJ. Randomized discontinuation design: application to cytostatic antineoplastic agents. J. Clin. Oncol. 20(22), 4478-4484 (2002).
44. Stadler WM, Rosner G, Small E et al. Successful implementation of the randomized discontinuation trial design: an application to the study of the putative antiangiogenic agent carboxyaminoimadazole in renal call carcinoma - CALGB 69901. J. Clin. Oncol. 23(16), 3726-3732 (2005).
45. Freidlin B, Simon R. Evaluation of randomized discontinuation design. J. Clin. Oncol. 23(22), 5094-5098 (2005).
46. Capra WB. Comparing the power of the discontinuation design to that of the classic randomized design on time-to-event endpoints. Cont. Clin. Trials 25(2), 168-177 (2004).
47. Fu P, Dowlati A, Schluchter M. Comparison of power between randomized discontinuation design and upfront randomization design on progression-free survival. J. Clin. Oncol. 27(25), 4135-4141 (2009).
48. Ellenberg SS, Eisenberger MA. An efficient design for Phase III studies of combination chemotherapies. Cancer Treat. Rep. 69(10), 1147-1154 (1985).
49. Inoue LY, Thall PF, Berry DA. Seamlessly expanding a randomized Phase II trial to Phase III. Biometrics 58(4), 823-831 (2002).
50. Van Glabbeke M, Steward W, Armand JP. Non-randomized Phase II trials of drug combinations: often meaningless, sometimes misleading. Are there alternative strategies? Eur. J. Cancer 38(5), 635-638 (2002).
51. Wieand HS. Randomized Phase II trials: what does randomization gain? J. Clin. Oncol. 23(9), 1794-1795 (2005).
52. Redman M, Crowley J. Small randomised trials. J. Thorac. Oncol. 2(1), 1-2 (2007).
53. Booth CM, Calvert AH, Giaccone G, Lobbezoo MW, Eisenhauer EA, Seymour LK. Design and conduct of Phase II studies of targeted anticancer therapy: recommendations from the task force on methodology for the development of innovative cancer therapies (MDICT). Eur. J. Cancer 44(1), 25-29 (2008).
54. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther. 69(3), 89-95 (2001).
55. McShane LM, Hunsberger S, Adjei AA. Effective incorporation of biomarkers in Phase II trials. Clin. Cancer Res. 15(6), 1898-1905 (2009).
56. Park JW, Stagg R, Lewis GD et al. Anti-p185 HER2 monoclonal antibodies: biological properties and potential for immunotherapy. In: Genes, Oncogenes and Hormones: Advances in Cellular and Molecular Biology of Breast. Dickson RB, Lippman ME (Eds). Kluwer, MA, USA 193-211 (1992).
57. Lewis GD, Figari I, Fendly B et al. Differential responses of human tumor cell lines to anto-p185HER2 monoclonal antibodies. Cancer Immunol. Immunother. 37(4), 255-257 (1993).
58. Baselga J, Tripathy D, Mendelsohn J et al. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu overexpressing metastatic breast cancer. J. Clin. Oncol. 14(3), 737-744 (1996).
59. Cobleigh MA, Vogel CL, Tripathy D et al. Multinational study of the efficacy and safety of humanized antiHER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J. Clin. Oncol. 17(9), 2639-2648 (1999).
60. Wilhelm SM, Carter C, Tang L et al. BAY 43-9006 exhibits broad spectrum, oral antitumor activity and targets the RAF/ MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 64(19), 7099-7109 (2004).
61. Korn EL, Albert PS, McShane LM. Assessing surrogates as trial endpoints using mixed models. Stat. Med. 24(2), 163-182 (2005).
62. Van Den Abbeele AD. The lesions of GIST- PET and PET/CT: a new paradigm for imaging. Oncologist 13(Suppl. 2), 8-13 (2008).
63. Morgan B, Thomas AL, Drevs J et al. Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ Zk222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two Phase I studies. J. Clin. Oncol. 21(21), 3955-3964 (2003).
64. Lynch TJ, Bell DW, Sordella R et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to gefitinib. N. Engl. J. Med. 350(21), 2129-2139 (2004).
65. Thall PF, Simon R. Practical Bayesian guidelines for Phase IIB clinical trials. Biometrics 50(2), 337-349 (1994).
66. Tan SB, Machin D. Bayesian two-stage designs for Phase II clinical trials. Stat. Med. 21(14), 1991-2012 (2002).
67. Leung S, Wang YG. A Bayesian decision approach for sample size determination in Phase II trials. Biometrics 57(1), 309-312 (2001).
68. Berry DA. Bayesian clinical trials. Nat. Rev. Drug Discov. 5(1), 27-36 (2006).
69. Chugh R, Wathen JK, Maki RG et al. Phase II multicenter trial of imatinib in 10 histologic subtypes of sarcoma using a Bayesian hierarchical statistical model. J. Clin. Oncol. 27(19), 3148-3153 (2009).
70. Tan S-B, Machin D, Tai B-C, Foo K-F, Tan E-H. A Bayesian re-assessment of two Phase II trials of gemcitabine in metastatic nasopharyngeal cancer. Br. J. Cancer 86(6), 843-850 (2002).
71. Thall PF, Wathen JK. Practical Bayesian adaptive randomisation in clinical trials. Eur. J. Cancer 43(5), 859-866 (2007).
72. Berry DA, Eick SG. Adaptive assignment versus balanced randomization in clinical trials: a decision analysis. Stat. Med. 14(3), 231-246 (1995).
73. Giles FJ, Kantarjian HM, Cortes JE et al. Adaptive randomised study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukaemia. J. Clin. Oncol. 21(9), 1722-1727 (2003).
74. Maki RG, Wathen JK, Patel SR et al. Randomised Phase II study of gemcitabine and docetaxel compared with gemcitabine along in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002. J. Clin. Oncol. 25(19), 2755-2763 (2007).
75. Zhou X, Liu S, Kim ES, Herbst R, Lee JJ. Bayesian adaptive design for targeted therapy development in lung cancer - a step toward personalized medicine. Clinical Trials 5(3), 181-193 (2008).
76. Kim ES, Herbst RS, Lee JJ et al. Phase II randomized study of biomarker-directed treatment for non-small cell lung cancer (NSCLC): The BATTLE (Biomarker- Integrated Approaches of Targeted Therapy for Lung Cancer Elimination) clinical trial program. J. Clin. Oncol. 27(Suppl. 15), (2009) (Abstract 8024).
77. Adjei AA, Christian M, Ivy P. Novel designs and end points for Phase II clinical trials. Clin. Cancer Res. 15(6), 1866-1872 (2009).
78. Mok TS, Wu Y-L, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med. 361(10), 947-957 (2009).