Phase I Clinical Trials with Anticancer Agents

  • Stephen Leong
  • Justin Call
  • Alex A. Adjei
  • Wells Messersmith
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Although the term “phase I” is used to describe numerous trial designs, the overarching goal of a phase I study is to determine the optimal dose and/or schedule of a therapy for evaluation in the phase II setting. Phase I trials typically test different doses of an anticancer agent(s) in various neoplastic diseases, with safety evaluation as a main objective. These studies range from first-in-human trials of novel single agents to new combinations of FDA-approved therapies. Frequently, pharmacokinetic studies are incorporated in phase I clinical trials, in order to determine drug exposure and clearance. In addition, phase I studies may include biomarkers of drug effects such as functional imaging or direct measurement of drug effects on either tumor biopsies and/or normal tissue samples.


Dose Level Dose Escalation Oncology Trial Human Equivalent Dose Animal Dose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Roberts TG, Jr., Goulart BH, Squitieri L, et al: Trends in the risks and benefits to patients with cancer participating in phase 1 clinical trials. JAMA 292:2130–40, 2004PubMedCrossRefGoogle Scholar
  2. 2.
    Simon R, Freidlin B, Rubinstein L, et al: Accelerated titration designs for phase I clinical trials in oncology. J Natl Cancer Inst 89:1138–47, 1997PubMedCrossRefGoogle Scholar
  3. 3.
    O’Quigley J, Pepe M, Fisher L: Continual reassessment method: a practical design for phase 1 clinical trials in cancer. Biometrics 46:33–48, 1990PubMedCrossRefGoogle Scholar
  4. 4.
    Chevert S: The continual reassessment method in cancer phase I clinical trials: a simulation study. Stat Med 12:1093–108, 1993CrossRefGoogle Scholar
  5. 5.
    Goodman SN, Zahurak ML, Piantadosi S: Some practical improvements in the continual reassessment method for phase I studies. Stat Med 14:1149–61, 1995PubMedCrossRefGoogle Scholar
  6. 6.
    Koyfman SA, Agrawal M, Garrett-Mayer E, et al: Risks and benefits associated with novel phase 1 oncology trial designs. Cancer 110:1115–24, 2007PubMedCrossRefGoogle Scholar
  7. 7.
    Skolnik JM, Barrett JS, Jayaraman B, et al: Shortening the timeline of pediatric phase I trials: the rolling six design. J Clin Oncol 26:190–5, 2008PubMedCrossRefGoogle Scholar
  8. 8.
    Mahmoud HH, Hurwitz CA, Roberts WM, et al: Tretinoin toxicity in children with acute promyelocytic leukaemia. Lancet 342:1394–5, 1993PubMedCrossRefGoogle Scholar
  9. 9.
    Eisenhauer EA, O’Dwyer PJ, Christian M, et al: Phase I clinical trial design in cancer drug development. J Clin Oncol 18:684–92, 2000PubMedGoogle Scholar
  10. 10.
    Von Hoff DD, Turner J: Response rates, duration of response, and dose response effects in phase I studies of antineoplastics. Invest New Drugs 9:115–22, 1991Google Scholar
  11. 11.
    Mahmood I: A Bayesian approach for the estimation of pharmacokinetic parameters in children. Am J Ther 10:88–92, 2003PubMedCrossRefGoogle Scholar
  12. 12.
    Contrera JF, Matthews EJ, Kruhlak NL, et al: Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose. Regul Toxicol Pharmacol 40:185–206, 2004PubMedCrossRefGoogle Scholar
  13. 13.
  14. 14.
    Shankar LK, Hoffman JM, Bacharach S, et al: Consensus recommendations for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials. J Nucl Med 47:1059–66, 2006PubMedGoogle Scholar
  15. 15.
    Parulekar WR, Eisenhauer EA: Phase I trial design for solid tumor studies of targeted, non-cytotoxic agents: theory and practice. J Natl Cancer Inst 96:990–7, 2004PubMedCrossRefGoogle Scholar
  16. 16.
    Agrawal M, Emanuel EJ: Ethics of phase 1 oncology studies: reexamining the arguments and data. JAMA 290:1075–82, 2003PubMedCrossRefGoogle Scholar
  17. 17.
    Freireich EJ: Ethical considerations in cancer chemotherapy. Annu Rev Pharmacol Toxicol 19:547–57, 1979PubMedCrossRefGoogle Scholar
  18. 18.
    Joffe S, Miller FG: Rethinking risk-benefit assessment for phase I cancer trials. J Clin Oncol 24:2987–90, 2006PubMedCrossRefGoogle Scholar
  19. 19.
    Lipsett MB: On the nature and ethics of phase I clinical trials of cancer chemotherapies. JAMA 248:941–2, 1982PubMedCrossRefGoogle Scholar
  20. 20.
    Horstmann E, McCabe MS, Grochow L, et al: Risks and benefits of phase 1 oncology trials, 1991 through 2002. N Engl J Med 352:895–904, 2005PubMedCrossRefGoogle Scholar
  21. 21.
    Daugherty CK, Banik DM, Janish L, et al: Quantitative analysis of ethical issues in phase I trials: a survey interview of 144 advanced cancer patients. IRB 22:6–14, 2000PubMedCrossRefGoogle Scholar
  22. 22.
    Joffe S, Cook EF, Cleary PD, et al: Quality of informed consent: a new measure of understanding among research subjects. J Natl Cancer Inst 93:139–47, 2001PubMedCrossRefGoogle Scholar
  23. 23.
    Horng S, Emanuel EJ, Wilfond B, et al: Descriptions of benefits and risks in consent forms for phase 1 oncology trials. N Engl J Med 347:2134–40, 2002PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Stephen Leong
  • Justin Call
  • Alex A. Adjei
    • 1
  • Wells Messersmith
  1. 1.Department of MedicineRoswell Park Cancer InstituteBuffaloUSA

Personalised recommendations