A Phase I and Pharmacokinetic Study of Clofarabine in Adult Patients With Advanced Solid Tumors

Inclusion Criteria:

- Have a pathologic diagnosis of advanced solid tumors

- After MTD is established, patients must have a measurable disease per Response
Evaluation Criteria in Solid Tumors (RECIST) criteria

- Be greater than or equal to 18 years old

- Not eligible for therapy of higher curative potential

- Have a Karnofsky Performance Status (KPS) greater than or equal to 70

- Have an estimated life expectancy of greater than or equal to 12 weeks

- Have a negative serum or urine pregnancy test within 7 days of study enrollment (if
patient is a female of childbearing potential)

- Male and female patients who are fertile must agree to use an effective barrier
method of birth control (latex condom, diaphragm, cervical cap, etc.) to avoid
pregnancy

- Sign a written informed consent form

- Able to comply with study procedures and follow-up examinations

- Have adequate organ function as indicated by the following laboratory values,
obtained within 2 weeks prior to registration: ANC: greater than or equal to 1.5 × 10
9th/L; Platelets: greater than or equal to 100 × 10 9th/L; Serum bilirubin: less
than 2.0 mg/dL; AST and ALT: less than 3 x ULN (Institutional Upper Limit of Normal)
without liver involvement OR less than 5 x ULN(*) with liver involvement; Serum
creatinine: less than 2.0 mg/dL; Echocardiogram shortening fraction: greater than or
equal to 28%(Not on pharmacologic support); or Ejection fraction greater than or
equal to 50% (Not on pharmacologic support).

Exclusion Criteria:

- Received previous treatment with clofarabine.

- Have an active, uncontrolled systemic infection considered opportunistic, life
threatening, or clinically significant at the time of treatment.

- Prior malignancy with less than a 2-year disease-free interval, except for adequately
treated basal cell or squamous cell skin cancer; or in situ cancer of the cervix.

- Are pregnant or lactating.

- Have a psychiatric disorder(s) that would interfere with consent, study
participation, or follow-up.

- Have received any chemotherapy, major surgery, or irradiation, whether conventional
or investigational, < 4 weeks before enrollment in this study (6 weeks for
mitomycin-C or nitrosourea) and/or have not recovered from acute toxicities of all
previous therapy prior to enrollment.

- Have any other severe concurrent disease, which, in the judgment of the investigator,
would make the patient inappropriate for entry into this study (eg, uncontrolled
severe insulin-dependent diabetes, uncontrolled hypertension, transient ischemic
attacks, uncontrolled symptomatic coronary artery disease, etc.).

- Have received prior radiation therapy to greater than or equal to 25% of the bone
marrow (eg, no whole pelvic irradiation is allowed) and have not recovered from the
acute side effects of radiotherapy.

- Have received prior radiation therapy to the mediastinal region.

- Have a broncho-alveolar pattern evident on chest x-ray.

- Have symptomatic or untreated central nervous system (CNS) metastases.