R-(-)-Gossypol Acetic Acid in Treating Patients With Recurrent Extensive-Stage Small Cell Lung Cancer
Condition: Extensive Stage Small Cell Lung Cancer; Recurrent Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Recurrence
Intervention: R-(-)-gossypol acetic acid; pharmacological study; laboratory biomarker analysis
Intervention description: Given orally; Correlative studies; Correlative studies
Intervention MeSH terms: Acetic Acid; Retinol acetate; Gossypol acetic acid; Gossypol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well R-(-)-gossypol acetic acid works in treating
      patients with recurrent extensive-stage small cell lung cancer. Drugs used in chemotherapy,
      such as R-(-)-gossypol acetic acid, work in different ways to stop the growth of tumor cells,
      either by killing the cells or by stopping them from dividing.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed small cell lung cancer

               -  Extensive stage disease

               -  Recurrent disease

          -  Measurable disease

          -  Chemotherapy-sensitive disease, defined as:

               -  No progression during first-line chemotherapy

               -  No disease recurrence < 2 months after completion of first-line chemotherapy

          -  Must have received prior platinum-based chemotherapy

          -  No symptomatic or progressive brain metastases

               -  Patients with previously treated brain metastases who are clinically and
                  radiographically stable or improved and have been off steroids ≥ 14 days are
                  eligible

          -  ECOG performance status 0-2

          -  Life expectancy > 12 weeks

          -  Leukocytes ≥ 3,000/μL

          -  ANC ≥ 1,500/μL

          -  Platelet count ≥ 100,000/μL

          -  Total bilirubin < 1.5 mg/dL

          -  AST and ALT ≤ 2.5 times upper limit of normal

          -  Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min

          -  Hemoglobin > 8 g/dL

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception before, during, and for 30 days
             after completion of study therapy

          -  Able to take oral medications on a regular basis

          -  Willing to provide blood samples for mandatory correlative studies

          -  No condition that impairs the ability to swallow and retain R-(-)-gossypol tablets,
             including the following:

               -  Gastrointestinal tract disease resulting in an inability to take oral medication
                  or a requirement for IV alimentation

               -  Active peptic ulcer disease

          -  No malabsorption syndrome or disease significantly affecting gastrointestinal function

          -  No ulcerative colitis, inflammatory bowel disease, or a partial or complete small
             bowel obstruction

          -  No uncontrolled concurrent illness including, but not limited to, any of the
             following:

               -  Ongoing or active infection

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia

               -  Psychiatric illness or social situations that would limit compliance with study
                  requirements

          -  No symptomatic hypercalcemia > grade 2

          -  No requirement for routine use of hematopoietic growth factors (including G-CSF,
             GM-CSF, or IL-11) or platelet transfusions to maintain ANC or platelet counts

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to R-(-)-gossypol

          -  No HIV positivity

          -  Recovered from all prior therapy, including prior surgical procedures

          -  No prior surgical procedures affecting absorption

          -  No prior resection of the stomach or small bowel

          -  No more than one prior chemotherapy regimen

          -  No prior racemic gossypol or R-(-)-gossypol

          -  At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)

          -  At least 4 weeks since prior radiotherapy, hormonal agents, or biologic response
             modifiers

          -  At least 4 weeks since prior and no concurrent investigational agents or devices

          -  No concurrent prophylactic hematopoietic growth factors (including filgrastim [G-CSF],
             sargramostim [GM-CSF], or interleukin-11 [IL-11]) during course one

          -  No concurrent combination antiretroviral therapy for HIV-positive patients