Temozolomide With or Without Veliparib in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer
Condition: Recurrent Small Cell Lung Carcinoma
MeSH terms: Small Cell Lung Carcinoma
Intervention: Laboratory Biomarker Analysis; Placebo; Temozolomide; Veliparib
Intervention description: Correlative studies; Given PO; Given PO; Given PO
Intervention MeSH terms: Temozolomide; Veliparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 97.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well temozolomide with or without veliparib works
      in treating patients with small cell lung cancer that has returned or does not respond to
      treatment. Temozolomide works by damaging molecules inside the cancer cells, such as
      deoxyribonucleic acid (DNA), that are needed for cancer survival and growth. Veliparib may
      stop the growth of tumor cells by blocking proteins that are needed for repairing the damaged
      DNA and it may also help temozolomide to kill more cancer cells. It is not yet know whether
      temozolomide is more effective with or without veliparib in treating patients with relapsed
      or refractory small cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed small cell lung cancer;
             confirmation will be done at Memorial Sloan-Kettering Cancer Center (MSKCC) or locally
             for participating sites

          -  Patients' disease has relapsed or progressed after one or two prior chemotherapy
             regimens, one of which must have been an etoposide-platinum doublet; eligible patients
             will be defined as follows:

               -  "Sensitive" disease: patients who had one previous line of chemotherapy and
                  maintained an appropriate response for > 60 days

               -  "Refractory" disease: those patients with either (a) no response to first-line
                  chemotherapy or progression =< 60 days after completing treatment, or (b)
                  "sensitive" or "refractory" disease in need of third-line therapy (i.e. completed
                  or failed two previous lines of chemotherapy)

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

          -  Patients with asymptomatic brain metastases that do not require immediate whole brain
             radiation therapy and are on stable doses of steroids are allowed

          -  Patients must have measurable disease, which is defined as at least one lesion that
             can be accurately measured in at least one dimension on a computed tomography (CT)
             scan as per RECIST version 1.1; brain metastases can be considered measurable disease
             if they meet this criterion

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin >= 8.5 g/dL; the use of transfusion to achieve this criterion should be at
             the discretion of the investigators

          -  Total bilirubin =< 1.5 mg/dL x institutional upper limit of normal

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 3.0 x institutional upper limit of normal

          -  Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 50
             mL/min/1.73 m^2 for patients with creatinine levels >= 1.5 x upper limit of
             institutional normal

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

          -  For women of child-bearing potential, negative pregnancy test within 14 days prior to
             starting temozolomide and ABT-888

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Able to swallow pills

          -  Patients will not be excluded based on the diagnosis of acquired immune deficiency
             syndrome (AIDS); given the increased risk of infection, these patients should have
             cluster of differentiation (CD)4 counts above 200 cells/mm^3; patients with AIDS or
             human immunodeficiency virus (HIV) not receiving agents with the potential for
             pharmacokinetic interactions with ABT-888 may be eligible

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 3 weeks prior to entering
             the study

          -  Patients who have not recovered from adverse events due to agents administered more
             than 3 weeks earlier; toxicities should have resolved to baseline or to within one
             grade level of their baseline (not to exceed grade 2)

          -  Patients who have been administered ABT-888, any other PARP-inhibitor, or temozolomide

          -  Patients may not be receiving any other investigational agents

          -  Patients with leptomeningeal involvement

          -  Patients with active seizures or a history of seizures

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ABT-888 or temozolomide

          -  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; breastfeeding should be discontinued if
             the mother is treated with ABT-888; these potential risks also apply to temozolomide

          -  Patients with either AIDS or HIV on combination antiretroviral therapy are ineligible

          -  Patients with a synchronous active malignancy requiring treatment