An Open Label, Multicenter Phase I Study Of Selective Cyclin Dependent Kinase Inhibitor P1446A-05 In Subjects With Advanced Refractory Malignancies
1. Subjects must have histologically and/ or cytologically confirmed solid malignant
tumor or hematologic malignancy that is refractory to currently available treatment
or for which no standard treatment exists
2. Subjects of either sex and more than or equal to 18 years of age
3. ECOG (Eastern Cooperative Oncology Group) performance status less than or equal to 2
4. Subjects with life expectancy of at least 4 months
5. Hemoglobin greater than or equal to 8 g/dl
6. Absolute neutrophil count greater than or equal to 1000/mm3
7. Platelet count greater than or equal to 50,000/ mm3
8. Total bilirubin less than or equal to 1.5 X institutional upper limit of normal (ULN)
9. AST/ALT less than or equal to 3 X institutional upper limit of normal (ULN)
10. Creatinine less than or equal to 1.5 X institutional upper limit of normal (ULN)
11. Ability to understand and willingness to sign a written informed consent document.
1. Subjects who have received radiotherapy, chemotherapy or biologic/targeted anticancer
agents within 4 weeks prior to day 1 of study drug administration (6 weeks for
nitrosoureas or mitomycin C) or have not recovered completely from adverse effects of
any prior radiotherapy, chemotherapy or biologic/targeted agents
2. Subjects who have received autologous or allogeneic bone marrow transplant within 6
months of day 1 of study drug administration
3. Subjects with known brain metastases at the time of screening
4. Subjects who had received any other investigational drug within 1 month or within
five half-lives of the other investigational agent, whichever is longer prior to day
1 of study drug administration or who have not completely recovered from adverse
effects of the investigational agent received prior to this period.
5. History of allergic reactions attributed to compounds of similar chemical structure
6. Subjects on immunosuppressive therapy.
7. History of unstable angina or myocardial infarction or stroke within previous 6
8. Subjects with uncontrolled inter-current illness including, but not limited to active
infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.
9. Subjects known to be suffering from infection with HIV, Tuberculosis, Hepatitis C or
10. History of any other prior malignancy except for curatively treated basal cell or
squamous cell carcinoma of skin, in situ cervical cancer, in situ breast cancer, in
situ prostate cancer or any other cancer for which the subject has been diseasefree
for at least 3 years.
11. Women who are pregnant or lactating.
12. Women of childbearing potential [defined as a sexually mature woman who has not
undergone hysterectomy or who has not been naturally postmenopausal for at least 24
consecutive months (i.e. who has had menses any time in the preceding 24 consecutive
months)] and men, not agreeing to use adequate contraception (e.g., hormonal or
barrier method of birth control or abstinence) prior to study entry (after signing
the informed consent document), during the duration of study participation and for at
least 4 weeks after withdrawal from the study, unless they are surgically sterilised.
13. Any condition, including laboratory abnormalities, that in the opinion of the
investigator places the subject at an unacceptable risk or deems the subject not
suitable for participation in the study.