Study of Arsenic Trioxide in Small Cell Lung Cancer
Condition: Lung Cancer; Cancer of Lung; Pulmonary Cancer; Pulmonary Neoplasms; Carcinoma, Small Cell
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Carcinoma, Small Cell
Intervention: Arsenic Trioxide
Intervention description: Drug will be given as a loading dose of 0.32mg/kg/day for 4 days in Week 1, followed by 0.25mg/kg/day twice per week for 5 weeks, followed by 2 weeks of rest, at which time response assessment will be performed. Patients will be restaged prior to the beginning of a new cycle, every 2 months on average. Maximum of 6 cycles of therapy will be administered in the absence of tumor progression or excessive side effects
Intervention MeSH terms: Arsenic Trioxide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lung Cancer; Carcinoma, small cell; Trisenox; Arsenic trioxide; phase II trial

Summary:

      The purpose of this study is to study the effect of an anticancer drug, Arsenic Trioxide, in
      patients with small cell lung cancer who have failed at least one standard chemotherapy
      regimen as well as patients who are unable to tolerate the standard treatment for their
      cancer. The investigators seek to establish the safety of and efficacy of Arsenic Trioxide in
      this patient group. The study will include up to 36 participants with small cell lung cancer.

      The investigators want to find out what effects, good or bad, that the study drug has on your
      cancer. This study will also look at specific biomarkers in your blood and in the tumor
      tissue which may help the investigators to determine if the levels of these biomarkers are
      related to tumor response to treatment.

      Arsenic Trioxide, also known by the brand name, Trisenox, is a chemotherapy drug approved by
      the Food and Drug Administration (FDA) for the treatment of a specific type of blood cancer
      called Acute Promyelocytic Leukemia. It works in part by making cancer cells become more
      mature thereby stopping them from growing in number and more likely to die off.
    

Eligibility criteria:

        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.

          -  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

          -  Eastern Cooperative Oncology Group (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

               -  aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 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., granulocyte-colony stimulating factor [G-CSF],
             granulocyte-macrophage colony-stimulating factor [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, ductal carcinoma in situ (DCIS), early stage prostate cancer
             without detectable prostate-specific antigen (PSA) or excised carcinoma in situ of the
             cervix

          -  Patient is unable or unwilling to abide by the study protocol