Clinical Trial Designs for Approval of New Anticancer Agents
There is an imperative need for development of newer cancer therapeutics and their rapid availability for cancer patients. Better clinical trial designs may help cancer therapeutics become available for treatment sooner. This chapter focuses on our present knowledge about clinical trial design, discussions of successful trial designs, as well as proposals for novel strategies. An exhaustive review of methods used to select agents which are currently in use is included and followed by a summary table of all of the new agents considered by the Food and Drug Administration’s Oncologic Drug Advisory Committee, including the type of trial performed, approved versus disapproved, and the primary endpoint used for approval. Novel clinical trial design suggestions have been included. We hope the present effort helps readers understand various clinical trial designs and get them enthusiastic about exploring new designs.
KeywordsAntineoplastic agents Drug therapy Clinical trial Drug approval Drugs Investigational Drug evaluation
This work was supported by the National Foundation for Cancer Research, Center for New Therapies Development (DVH), and by the Drug Development Scholar Program from The Scottsdale Healthcare Foundation (MKC) and Translational Drug Development Institute (TGen) (DVH).
- 11.O’Shaughnessy J, Osborne C, Pippen J et al (2009) Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): results of a randomized phase II trial. J Clin Oncol 27:18s (suppl; abstr 3)CrossRefGoogle Scholar
- 30.Twelves C, Loesch D, Blum JL et al (2010) A phase III study (EMBRACE) of eribulin mesylate versus treatment of physician’s choice in patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 28:18s (suppl; abstr CRA1004)Google Scholar
- 31.Von Hoff DD (1998) There are no bad anticancer agents, only bad clinical trial designs – twenty-first Richard and Hinda Rosenthal Foundation Award Lecture. Clin Cancer Res 4(5):1079–1086Google Scholar
- 32.Saltz L, Rubin M, Hochster H et al (2001) Cetuximab (IMC-C225) plus irinotecan (CPT-11) is active in CPT-11-refractoy colorectal cancer (CRC) that expresses epidermal growth factor receptor (EGFR). Proc Annu Meet Am Soc Clin Oncol 20:3a, abstract 7Google Scholar
- 36.DeVore RF, Fehrenbacher L, Herbst R et al (2000) A randomized Phase II trial comparing rhumab VEGF (recombinant humanized monoclonal antibody to vascular endothelial cell growth factor) plus carboplatin/paclitaxel (CP) to CP alone in patients with stage IIB/IV NSCLS. Proc Annu Meet Am Soc Clin Oncol 19:485a, abstract 1896Google Scholar
- 37.Findlay M, Van Cutsem E, Kocha W et al (1997) A randomised phase II study of XelodaTM (capecitabine) in patients with advanced colorectal cancer. Proc Annu Meet Am Soc Clin Oncol 16:227a, abstract 798Google Scholar
- 43.Schultz RM, Merriman RL, Toth JE et al (1993) Evaluation of new anticancer agents against the MIA PaCa- 2 and PANC-1 human pancreatic carcinoma xenografts. Oncol Res 3:223–228Google Scholar
- 45.Anderson JS, Burris HA, Casper E (1994) Development of a new system for assessing clinical benefit for patients with advanced pancreatic cancer. Proc Annu Meet Am Soc Clin Oncol 13:461, abstract 1600Google Scholar
- 52.Alberts DS, Green S, Hannigan EV et al (1992) Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer. J Clin Oncol 10:706–717PubMedGoogle Scholar
- 54.Stewart DJ, Kurzrock R (2009) Cancer: the road to Amiens. Clin Oncol 27(3):328–333Google Scholar