7-hydroxystaurosporine and Topotecan Hydrochloride in Treating Patients With Relapsed or Progressed Small Cell Lung Cancer
Condition: Extensive Stage Small Cell Lung Cancer; Recurrent Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: topotecan hydrochloride; 7-hydroxystaurosporine
Intervention description: Given IV; Given IV
Intervention MeSH terms: Topotecan; 7-hydroxystaurosporine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving UCN-01 together with topotecan works in
      treating patients with small cell lung cancer that relapsed or progressed after previous
      chemotherapy. Drugs used in chemotherapy, such as topotecan, work in different ways to stop
      the growth of tumor cells, either by killing the cells or by stopping them from dividing.
      UCN-01 may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth. It may also increase the effectiveness of topotecan by making tumor cells more
      sensitive to the drug. Giving UCN-01 together with topotecan may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed extensive stage small cell lung cancer
             that is incurable but amenable to treatment with chemotherapy

          -  Patients must have measurable disease as defined by the Response Evaluation Criteria
             in Solid Tumours (RECIST); they must have either measurable disease outside the field
             or progression post radiation therapy

          -  Patient must have received ONLY first-line platinum-based chemotherapy and relapsed or
             progressed >= 3 months post completion of therapy (patients with chemo-sensitive
             disease)

          -  Patient must have completed any prior chemotherapy at least 3 months before study
             entry, have completed surgery or radiotherapy at least 4 weeks before study entry and
             must have recovered from the toxic effects from any prior therapy; patient must not
             have had more than 40% of their bone marrow radiated

          -  ECOG performance status =< 2 (Karnofsky >= 60%)

          -  Leucocytes >= 3 x 10^9/L OR

          -  ANC >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Total serum bilirubin =< 1.5 x UNL

          -  AST/ALT =< 3 x UNL (=< 5 x UNL if documented liver metastases)

          -  Creatinine =< institutional upper limit of normal OR creatinine clearance >= 50
             ml/min/1.73m^2 for patients with creatinine levels above institutional normal

          -  The effects of UCN-01 on the developing human fetus are unknown; for this reason,
             women of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control) prior to study entry and for the
             duration of study participation; contraception should be continued at least 3 months
             after the last dose of UCN-01; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had prior therapy with a topoisomerase I inhibitor (topotecan or
             irinotecan) will be excluded

          -  Patients who have had other chemotherapy regimens other than first-line platinum-based
             chemotherapy will be excluded

          -  Patients may not be receiving any other investigational agents

          -  Patients may not be receiving concurrent radiation therapy while on study treatment

          -  Patients with uncontrolled/symptomatic CNS metastases; routine CT scans are not
             required to rule these out except when there is clinical suspicion of CNS disease

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to UCN-01 or other agents used in study

          -  Because of cardiopulmonary toxicity seen in patients on other studies, patients with a
             history of coronary artery disease and/or symptomatic cardiac dysfunction should be
             excluded

          -  Because UCN-01 may cause hyperglycemia, patients with insulin dependent diabetes
             mellitus will be excluded; patients with diet-controlled diabetes mellitus or those on
             oral hypoglycemic agents can be entered at the discretion of the investigator

          -  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 UCN-01 is a serine-threonine
             kinase inhibitor with the potential for teratogenic or abortifacient effects; because
             there is an unknown but potential risk for adverse events in nursing infants secondary
             to treatment of the mother with UCN-01, breastfeeding should be discontinued if the
             mother is treated with UCN-01; these potential risks may also apply to other agents
             used in this study

          -  Because patients with immune deficiency are at increased risk of lethal infections
             when treated with marrow-suppressive therapy, HIV-positive patients receiving
             combination anti-retroviral therapy are excluded from the study because of possible
             pharmacokinetic interactions with UCN-01 or other agents administered during the
             study; appropriate studies will be undertaken in patients receiving combination
             anti-retroviral therapy when indicated

          -  Patients may not have had any other active malignancy in the past 5 years except for
             cervical carcinoma in situ and non-melanomatous skin cancer