A Multicenter Phase I Clinical Study of a New Compound P1446A-05 in Patients With Advanced Refractory Malignancies
A Multicenter Phase I Clinical Study of a New Compound P1446A-05 in Patients With Advanced Refractory Malignancies
This is a phase I study of a novel compound P1446A-05. Aim of this study is to identify the
 the recommended phase II dose of the drug and to determine the nature of adverse effects
 associated with the drug. P1446A-05 capsules will be given continuously (28 days in each 28
 day cycle) to patients suffering from advanced malignancies with no effective treatment
 available. The dose of the study agent will be lower i.e. 75 mg per day for initial patients.
 If this dose is found safe, higher dose will be administered to next set of (three to six)
 patients. This will continued till the safest and best dose is identified. Treatment will be
 given for 4 cycles and continued further if found effective. Dose schedule may be modified to
 introduce treatment holiday,if frequent adverse effects are seen on continuous
 administration.
Inclusion Criteria:

 -  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.

 Exclusion Criteria:

 -  autologous or allogeneic bone marrow transplant within 6 months of day 1 of study drug
 administration

 -  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 to
 P1446A-05.

 -  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
 B.

 -  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
 sterilised.

 -  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.