An Open Label, Multicenter Phase I Study Of Selective Cyclin Dependent Kinase Inhibitor P1446A-05 In Subjects With Advanced Refractory Malignancies
- Histologically and/ or cytologically confirmed solid malignant tumor or Malignant
Lymphoma (excluding CNS Lymphoma and multiple myeloma) that is refractory to
currently available treatment or for which no standard treatment exists
- Measurable disease
- Must have completed any prior chemotherapy, radiotherapy, biologic/targeted
anti-cancer therapy or surgery at least 4 weeks (at least 6 weeks for nitrosureas and
mitomycin C; 3 months for monoclonal antibodies, radioactive monoclonal antibodies or
any radio- or toxin- immunoconjugates) before study entry and subjects must have
recovered (to ≤grade 1) from the toxic effects from any prior therapy.
- Must not have had more than 40% of their bone marrow radiated and must have either
measurable disease outside the field or progression post radiation therapy.
- Age ≥ 18 years
- ECOG performance status ≤ 2
- Life expectancy of at least 12 weeks
- Normal organ and marrow function as defined below:
Hemoglobin >/= 90 g/L Leukocytes >/=3 x 109/L Absolute Neutrophil Count (ANC) >/=1.5 x
109/L Platelets >/=100 x 109/L Total bilirubin = 1.5 X institutional Upper Limit of
Normal (ULN) AST(SGOT) =2.5 X institutional ULN ALT(SGPT) =2.5 X institutional ULN
Creatinine =1.5 X institutional ULN
- Ability to understand and willingness to sign a written informed consent document.
- autologous or allogeneic bone marrow transplant within 6 months of day 1 of study
- Known brain metastases at the time of screening
- Any other investigational drug within 1 month prior to day 1 of study drug
administration or not recovered (to ≤grade 1) from adverse effects of the
investigational agent received prior to this period.
- History of allergic reactions attributed to compounds of similar chemical structure
- On immunosuppressive therapy.
- History of unstable angina or myocardial infarction or stroke within 6 months prior
to Day 1 of study drug administration.
- 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.
- Known to be suffering from infection with HIV, Tuberculosis, Hepatitis C or Hepatitis
- Pregnant or lactating women
- 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 (two methods of
contraception, including at least one barrier method, - i.e. : hormonal and a 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 drug, unless they are surgically
- 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.