A Phase I Open Label Safety, Pharmacokinetic and Pharmacodynamic Dose Escalation Study of SF1126, A PI3 Kinase (PI3K) Inhibitor, Given Twice Weekly By IV Infusion To Patients With Advanced or Metastatic Tumors
To qualify for enrollment, all of the following criteria must be met:
- Written informed consent.
- At least 18 years old.
- Accrual will be limited to patients with tumor types that in the opinion of the
investigator is known to have PTEN loss or PI3 Kinase mutations potentially important
in the biology of their cancer.
- Only patients with histologically confirmation of advanced solid malignant tumor
which is refractory to standard therapies or which no standard therapy exists.
- Eastern Cooperative Oncology Group Performance Status of 0 or 1.
- Life expectancy of > or = 12 weeks.
- Female subjects are eligible to enter and participate in the study if: they are
non-childbearing potential, had a hysterectomy, had a bilateral oophorectomy
(ovariectomy), had a bilateral tubal ligation, post-menopausal or childbearing
potential with a negative serum pregnancy test at screening and agrees to protection
by IUD, vasectomized partner, complete abstinence, double barrier contraception.
- male patients with childbearing potential must agree to use adequate contraception
while on study.
- patients on active therapy with well-controlled diabetes as defined by fasting
glucose < 160mg/dL.
- Brain metastases or spinal cord compression, unless treatment was completed at least
4 weeks before entry, and stable without steroid treatment for at least 4 weeks.
- Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count <1.5 x
10^9/L or platelet count < 100 x 10^9/L (can not be post-transfusion) or hemoglobin
<9 g/dL (can be post-transfusion).
- Serum bilirubin > or = 1.2 times the upper limit of normal.
- An ALT or AST level > or = 2.5 times the upper limit of normal. If documented liver
metastases are present, the ALT or AST levels must still be less than 2.5 times the
upper limit of normal.
- Serum creatinine > 1.5 times the upper limit of normal or a creatinine clearance of <
or = 50mL/min calculated by the Cockcroft-Gault equation.
- Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated
respiratory, cardiac [including life threatening arrhythmias], hepatic, or renal
- Unresolved toxicity ≥CTC Grade 2 from previous anti-cancer therapy except alopecia
(if applicable) unless agreed that the patient can be entered after discussion with
the Medical Monitor.
- QTc prolongation defined as a QTc >450 ms for males or >470ms for females
(Fridericia) for 3 consecutive ECGs; OR prior history of cardiovascular disease
including heart failure that meets New York Hearth Association (NYHA) class III and
IV definitions, OR history of myocardial infarction/active ischemic heart disease
within one year of study entry; OR uncontrolled dysrhythmias; OR poorly controlled
- Participation in a trial of an investigational agent within the prior 30 days.
- Pregnant or breast-feeding females.
- High volume peritoneal or pleural effusions requiring a tap more frequently than
every 14 days.
- History of other malignancies except curatively excised carcinoma in situ of the
cervix, non-melanomatous skin carcinoma or superficial bladder cancer or other solid
tumors curatively treated with no evidence of disease for > or = 5 years. Other
cases will be reviewed and possibly allowed if discussed with and approved by Medical
- Patients receiving therapeutic doses of Warfarin.
- Any concurrent condition which in the investigator's opinion makes it undesirable for
the subject to participate in this trial or which would jeopardize compliance with