Linsitinib or Topotecan Hydrochloride in Treating Patients With Relapsed Small Cell Lung Cancer
Condition: Recurrent Small Cell Lung Carcinoma
MeSH terms: Small Cell Lung Carcinoma
Intervention: Laboratory Biomarker Analysis; Linsitinib; Pharmacological Study; Topotecan Hydrochloride
Intervention description: Correlative studies; 150 mg given orally (PO) twice a day (BID); Correlative studies; 1.5 mg/m^2 intravenously (IV) or 2.3 mg/m^2 orally (PO)
Intervention MeSH terms: Topotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate how OSI-906 compares to Topotecan in trying to slow
      down the growth and/or progression of the tumors of participants with relapsed or recurrent
      Small Cell Lung Cancer.

      This study also plans to find out what effects, good or bad (side effects), OSI-906 has on
      participants and or Small Cell Lung Cancer. The study will also investigate if some proteins
      measured in the blood or tumor and some imaging features obtained from computed tomography
      (CT) scans can help predict whether OSI-906 or topotecan will be effective against Small Cell
      Lung Cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed SCLC

          -  Patients must have measurable disease; at least one lesion that can be accurately
             measured is required

          -  Patients must have progression of disease after receiving ONLY 1 previous
             platinum-containing regimen; prior treatment with biological response modifiers or
             targeted agents will NOT count towards this requirement; previous topotecan or any
             type of pharmacologic IGF-1R inhibition are NOT allowed

          -  Life expectancy of greater than 6 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2; (Karnofsky >=
             60%)

          -  Leukocytes (white blood cell [WBC]) >= 3,000/mcL OR

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin within normal institutional limits (NIL)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.0 times institutional upper limit of normal (ULN) without demonstrable liver
             metastases OR < 5.0 times ULN with liver metastases present

          -  Serum creatinine within NIL OR measured/calculated creatinine clearance (CrCl) >= 60
             mL/min/1.73 m^2 for patients with creatinine levels above NIL

          -  Fasting blood glucose < 160 mg/dL at baseline

          -  Patients on oral antihyperglycemic therapies may be enrolled provided they have been
             taking a stable dose of these medications for >= 2 weeks at the time of randomization

          -  Prior radiation is permitted IF the site(s) of measurable disease has progressed since
             prior irradiation and radiation is completed at least 2 weeks before initiation of
             drug treatment (stereotactic radiotherapy excluded)

          -  Patients with central nervous system (CNS) metastases are ELIGIBLE, provided that
             prior to drug treatment, the metastases have been treated, remain clinically or
             radiographically stable and the patient has no significant neurologic symptoms

          -  Patients must NOT have prior malignancy EXCEPT for the following: adequately treated
             basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
             stage I or II cancer from which the patient is currently in complete remission, or any
             other cancer from which the patient has been disease-free for >= 3 years

          -  Women of child-bearing potential (WOCBP) 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 she or her partner is participating in this study, she
             should inform her treating physician immediately; WOCBP must provide a negative
             pregnancy test (serum or urine) within 14 days prior to registration

          -  Available archival tumor tissue is NOT mandatory for enrollment (will be requested)

          -  Patients must have the ability to understand and the willingness to sign a written
             informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy within 3 weeks (6 weeks for nitrosoureas or
             mitomycin C) or radiotherapy 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 who are receiving any other investigational agents

          -  Patients with CNS metastases are NOT EXCLUDED, provided that prior to drug treatment,
             the metastases have been treated, remain radiographically stable and the patient has
             no significant neurologic symptoms

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to OSI-906 or other agents used in the study (topotecan)

          -  While cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2)
             inhibitors/inducers are not specifically excluded, investigators should be aware that
             the metabolism and consequently overall pharmacokinetics (PKs) of OSI-906 (OSI-906
             exposure) could be altered by concomitant use of these drugs (inhibitors, inducers
             and/or other substrates of CYP1A2); exception: potent CYP1A2 inhibitors ciprofloxacin
             and fluvoxamine are prohibited; while cytochrome P450, family 2, subfamily C,
             polypeptide 9 (CYP2C9) substrates are not specifically excluded, investigators should
             be aware that levels of drugs metabolized by CYP2C9 may be increased by the
             concomitant administration of OSI-906; caution should be used when administering
             CYP2C9 substrates to study patients

          -  The concomitant use of p-glycoprotein inhibitors with topotecan capsules is not
             allowed

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, significant cardiac disease (i.e., symptomatic congestive heart failure,
             unstable angina pectoris, symptomatic or life-threatening cardiac arrhythmia), or
             psychiatric illness/social situations that would limit compliance with study
             requirements

          -  Pregnant or breast-feeding women are excluded from this study

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible

          -  Patients in the following scenarios are excluded:

               -  Corrected QT (QTc) interval > 450 msec at baseline

               -  Concomitant drugs that prolong the QTc interval

               -  Use of drugs that have a known risk of causing Torsades de Pointes (TdP) within
                  14 days prior to randomization

               -  Fasting blood glucose >= 160 mg/dL at baseline; these patients can initiate
                  allowed oral antihyperglycemic therapies and be retested or rescreened 2 weeks
                  later to meet baseline fasting blood glucose criteria

               -  Concomitant use of insulin or insulinotropic medications

          -  Patients with cirrhosis of the liver are excluded from this study

          -  Archival tumor tissue is NOT mandatory for enrollment, but will be requested