A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL418 Administered Orally Daily to Subjects With Solid Tumors
1. The subject has a histologically confirmed solid tumor that is metastatic or
unresectable, for which standard curative or palliative measures do not exist or are
no longer effective, and there are no known therapies to prolong survival.
2. The subject has disease that is assessable by tumor marker, physical, or radiologic
3. The subject is ≥18 years old.
4. The subject's weight is ≥55 kg and ≤120 kg.
5. The subject has an ECOG (Eastern Cooperative Oncology Group) performance status ≤2.
6. The subject has adequate organ and marrow function.
7. For subjects who are to be enrolled into the expanded MTD cohort:
1. tumor tissue amenable to serial biopsy; and
2. additional informed consent.
8. The subject is capable of understanding the protocol and has signed the informed
9. Sexually active subjects (male and female) must use medically acceptable methods of
contraception during the course of the study.
10. Female subjects of childbearing potential must have a negative serum pregnancy test
11. The subject has a normal fasting blood glucose level at screening.
12. If a subject has received more than three prior regimens of cytotoxic chemotherapy,
more than two biological regimens, or more than 3000 cGy to areas containing
substantial marrow, the principal investigator (PI) and the sponsor will discuss
subject suitability prior to enrollment.
13. The subject has had no other diagnosis of malignancy (unless non-melanoma skin
cancer, in situ carcinoma of the cervix, or a malignancy diagnosed ≥5 years ago, with
no evidence of disease for 5 years prior to screening for this study).
1. The subject has received anticancer treatment (eg, chemotherapy, radiotherapy,
cytokines, or hormones) within 30 days (6 weeks for nitrosoureas or mitomycin C)
before the first dose of study drug.
2. The subject has received radiation to ≥25% of his or her bone marrow within 30 days
of treatment with XL418.
3. The subject has not recovered either to Grade ≤1 from adverse events (AEs) or to
within 10% of baseline values due to investigational or other agents administered
more than 30 days prior to study enrollment.
4. The subject has received another investigational agent within 30 days of the first
dose of study drug.
5. The subject has known brain metastases.
6. The subject is known to have diabetes.
7. The subject has an uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, hypertension, symptomatic congestive heart failure,
unstable angina pectoris, or cardiac arrhythmia.
8. The subject has psychiatric illness/social situations that would limit compliance
with study requirements.
9. The subject is pregnant or breast feeding.
10. The subject is known to be positive for the human immunodeficiency virus (HIV).
11. The subject has a known allergy or hypersensitivity to any of the components of the
12. The subject has a baseline QTc interval >450 ms.
13. The subject is unwilling or unable to abide by the study protocol or cooperate fully
with the investigator or designee.