therapy can be given. A brief explanation for missing data should be recorded as a comment. 
10.3 Accuracy of Data Collection: The Study Chairperson will be the final arbiter of response of 
toxicity should a difference of opinion exist. 
10.4 Statistical Considerations: A single arm study design will be used. It is assumed that the 
regrowth of the tumor occurs in 90% of patients (>25% increase in area). If the frequency of 
regrowth is reduced to 60% by the treatment, then using a one-sided test with 80% power and 
a=.05, a sample size of 14 patients is needed. It should be possible to accrue this number 
within 18 months. 
To prevent enrolling more patients in the trial when excessive toxicity is found, a Bayesian 
early stopping rule will be implemented. The design is described as follows: 
1) The toxicity is considered unacceptable at the level when more than one-third of the 
patients develop Grade 3 toxicity or when more than one-sixth of the patients develop 
Grade 4 toxicity. 
2) The probability of toxicity is assumed to follows the beta distribution with a non- 
informative prior [Uniform (0,1)]. 
3) The trial will be terminated when the probability of toxicity is greater than the 
undesired level [defined in (1)] with a high confidence. In this design, we choose this 
confidence probability being 0.90. 
Under the above specification, the trial will be stopped when the Grade 3 toxicity is observed in 
the following cases: (The number of toxicity is given in the numerator and the number of total 
cases in the denominator.) 2/2, 3/3, 3/4-5, 4/6-7, 5/8-9, 6/10-12, 7/13-14. 
The trial can also be stopped when the Grade 4 toxicity is observed in: 1/1-2, 2/3-6, 3/7-10, 
4/11-14. 
11.0 REPORTING REQUIREMENTS 
11.1 Any life-threatening and/or unexpected and serious (grade 3 or 4) toxicity will be reported 
immediately to the Study Chairperson who, in turn, must notify the Food and Drug Administration, 
Surveillance Conmittee, and the sponsoring agency. 
11.2 The Protocol Data management System will be used for data collections. 
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4. Shimizu K, Birnbaum D, Ruly MA, et al . Structure of the ki-ras gene of the human lung carcinoma cell 
line calu-1. Nature 1983; 304:497-500. 
5. Rodenhuis S, Van De Wetering ML, Mooi WJ, Evers SG, Van Zandwijk N, Bos JL. Mutational activation of the 
K-ras oncogene. N Enol J Med 1987; 317;15:929-935. 
6. Rodenhuis S, Slebos RJC, Boot AJM, et al . Incidence and possible clinical significance of K-ras oncogene 
activation in adenocarcinoma of the human lung. Cancer Res 1988;48:5738-5741. 
7. Reynolds SH, Anna CK, Brown KC, et al . Activated protooncogenes in human lung tumors from smokers. Proc 
Natl Acad Sci USA 1991; 88:1085-1089. 
8. Hollstein M, Sidransky 0, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991; 
253:49-53. 
9. Lane DP, Benchimol S. p53: oncogene or anti -oncogene? Genes & Develop 1990; 4:1-8. 
10. Bressac B, Galvin KM, Liang TJ, Isselbacher KJ, Wands JR. Abnormal structure and expression of p53 gene 
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