A Phase I Trial of Oral PX-866 (a PI-3K Inhibitor) in Patients With Advanced Solid Tumors
- Histologically or cytologically confirmed diagnosis of advanced solid tumor and has
failed or is intolerant of standard therapy, or for whom standard therapy does not
- 18 years of age or older.
- ECOG performance status 0 to 1.
- Predicted life expectancy of at least 12 weeks.
- Discontinued prior chemotherapy or other investigational agents for at least three
weeks prior to receiving the first dose of study drug (six weeks for mitomycin C,
nitrosureas,vaccines,or antibody therapy)and recovered from the toxic effects of the
prior treatment (recovered to baseline or ≤grade 1 per Common Toxicity Criteria for
Adverse Events (CTCAE)).
- Discontinued any radiation therapy for at least four weeks and have recovered from
all radiation-related toxicities (recovered to baseline or ≤CTCAE grade 1) prior to
receiving the first dose of study drug. Palliative radiation of 10 fractions or less
is permitted and a four week interval is not necessary (also allowed during therapy).
- Adequate hematologic function as defined by the following: WBC count >3,000
cells/μL; platelets >100,000/μL; hemoglobin >9 g/dL (may be transfused to this
level); ANC >1500 cells/μL.
- Adequate hepatic function as defined by the following: bilirubin <1.5 mg/dL;
aspartate aminotransaminase (AST/SGOT) & alanine aminotransferase (ALT/SGPT) <2.5 x
ULN or <5 x ULN if due to metastatic disease.
- Adequate renal function as defined by serum creatinine level <1.5 mg/dL.
- Any active infection at study entry.
- Known diabetes or fasting blood glucose>160 mg/dL.
- Known human immunodeficiency virus (HIV).
- Any serious concomitant systemic disorders that in the opinion of the investigator
would place the patient at excessive or unacceptable risk of toxicity.
- Surgery within the four weeks prior to the first dose
- Significant central nervous system (CNS) or psychiatric disorder(s) that preclude the
ability of the patient to provide informed consent.
- Known or suspected brain metastases that have not received adequate therapy or for
which the patient requires treatment with steroids or anticonvulsants. In the case of
previously treated brain metastases, a minimum four week interval between completion
of radiation therapy and registration on study with radiologic evidence of stable or
responding brain metastases is required. In the setting of previous CNS
metastasectomy, adequate (minimum four week) recovery from surgery and/or radiation
therapy should be documented.
- Leptomeningeal brain metastases should be excluded regardless of whether the
metastases have been treated or not.
- History of seizures, non-healing wounds, or arterial thrombosis.
- Unstable atrial or ventricular arrhythmias requiring control by medication; any
cardiac ischemic event experienced within the preceding six months; prior history of
congestive heart failure requiring therapy.
- Breastfeeding or pregnant (confirmed by serum β-HCG within 10 days prior to the start
of study treatment if applicable).
- Total gastrectomy, partial bowel obstruction or any gastrointestinal condition that
may interfere with absorption of the study medication.
- Any condition that could jeopardize the safety of the patient and compliance with the