A Single Arm, Two-Stage Phase II Study of Arsenic Trioxide in Previously Treated Small Cell Lung Cancer

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed small cell lung cancer

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded for
non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional
techniques or as >10 mm with spiral CT scan. See Section 11 for the evaluation of
measurable disease.

- Patient must have failed or found to be intolerant of standard frontline
platinum-based regimens. There is no limit on the number of prior regimens provided
the patient meets all the other eligibility criteria.

- Adult patients 18 years or older. Because no dosing or adverse event data are
currently available on the use of arsenic trioxide in patients <18 years of age,
children are excluded from this study but will be eligible for future pediatric
single-agent trials, if applicable.

- Life expectancy of greater than 3 months

- ECOG performance status of 0,1 or 2

- Patients must have normal organ and marrow function as defined below:

- absolute neutrophil count >1,500/mL

- platelets >100,000/mL

- total bilirubin ≤ 1.5 X institutional upper limits of normal

- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

- creatinine ≤ 1.5 X institutional upper limits of normal OR

- creatinine clearance >40 mL/min/1.73 m2 for patients with

- creatinine levels above institutional normal.

- Negative serum pregnancy test within 48 hours before starting study treatment in
women with childbearing potential

- Ability to understand and the willingness to sign a written informed consent
document.

- No history of QTc prolongation syndrome or any other cardiac conduction abnormality
evidenced by normal baseline EKG (QTc ≤450 in males and ≤470 in females)

- Both men and women and members of all races and ethnic groups are eligible for this
trial.

Exclusion Criteria:

- Need for treatment with chemotherapy (within 4 weeks; 6 weeks for nitrosoureas or
mitomycin C); radiotherapy or biologic agents (within 2 weeks) prior to entering the
study or those who have not recovered from adverse events due to agents administered
more than 4 weeks earlier.

- Patients may not be receiving any other investigational agents.

- Patients with uncontrolled symptomatic brain metastases. Patients with no known brain
metastasis are not required to undergo screening prior to enrolment.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to arsenic trioxide.

- 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.

- Pregnant women are excluded from this study because Trisenox is a category D agent
with the potential to cause fetal harm. Because there is an unknown but potential
risk for adverse events in nursing infants secondary to treatment of the mother with
Trisenox, breastfeeding should be discontinued if the mother is treated with
Trisenox.

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with Trisenox. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.

- Patients who require ongoing treatment with any hematopoietic colony-stimulating
growth factors (e.g., G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug.

- Patients who are currently receiving treatment with medication that has the potential
to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug

- Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy

- History of another malignancy within 3 years, except curatively treated basal cell
carcinoma of the skin, DCIS, early stage prostate cancer without detectable PSA or
excised carcinoma in situ of the cervix

- Patient is unable or unwilling to abide by the study protocol