Safety and Pharmacokinetics of XL647 Administered Orally to Subjects With Solid Tumors

A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL647 Administered Orally to Subjects With Solid Tumors

The primary objective of this study is as follows:

• To evaluate the safety and tolerability of XL647 administered orally as a single dose and as repeat doses in subjects with solid tumors.

The secondary objectives of this study are as follows:

• To evaluate the plasma pharmacokinetics of XL647 administered orally as a single dose and as repeat doses in subjects with solid tumors,
• To estimate renal elimination of XL647 administered orally as a single dose in subjects with solid tumors.

The exploratory objective of this study is as follows:

• To assess the pharmacodynamic effects of XL647 administration in plasma and peripheral blood cells.

In addition, subjects may be eligible to enter a Treatment Extension Period. The following information will be obtained from this part of the study:

• Long-term safety and tolerability of XL647 after repeat administration,
• Tumor response after repeat administration of XL647.

Inclusion Criteria:

• The subject has a histologically confirmed malignancy that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective,
• The subject has disease that is assessable by tumor marker, physical, or radiologic means,
• The subject is ≥18 years old,
• There have been at least 4 weeks since prior chemotherapy or radiation therapy (6 weeks if the last treatment regimen included BCNU or mitomycin C),
• The subject has an ECOG performance status ≤2 (Karnofsky >60%),
• The subject has a life expectancy of ≥3 months,
• The subject has normal organ and marrow function (hemoglobin >10g/dL, leukocytes >3,000/mL, absolute neutrophil count >1,500/µL, platelets >100,000/µL, total bilirubin within normal institutional limits of normal,AST (SGOT)/ALT(SGPT) <2.5 times the upper limit of normal, and creatinine within normal limits,
• The subject is capable of understanding and complying with the protocol and has signed the informed consent document,
• Sexually active subjects (both male and female) must use an accepted method of contraception during the course of the study,
• Female subjects of childbearing potential (pre-menopausal) must have a negative pregnancy test.

Exclusion Criteria:

• The subject has had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or has not recovered from AEs due to agents administered more than 4 weeks earlier,
• The subject has received another investigational agent within 30 days (or 5.5 half-lives) of the first dose of study drug,
• The subject has known brain metastases,
• The subject has a corrected QT interval (QTc) of >0.44 seconds,
• The subject has a history of allergic reactions attributed to aspartame or to any other component in the formulation vehicle,
• The subject has an uncontrolled intercurrent illness including,but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements,
• The subject is pregnant or nursing,
• The subject is known to be positive for the human immunodeficiency virus (HIV).