Linsitinib or Topotecan Hydrochloride in Treating Patients With Relapsed Small Cell Lung Cancer

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.

PRIMARY OBJECTIVES:

I. To compare the progression-free survival (PFS) of single-agent OSI-906 (linsitinib) to that of single-agent topotecan (topotecan hydrochloride) in patients with relapsed small cell lung cancer (SCLC).

SECONDARY OBJECTIVES:

I. To evaluate the response rate (RR), disease-control rate (DCR) and overall survival (OS) of single-agent OSI-906 in patients with relapsed SCLC.

II. To describe the toxicity profile of single-agent OSI-906 in this population.

TERTIARY OBJECTIVES:

I. To evaluate potential predictive biomarkers of OSI-906 sensitivity. II. To determine whether the baseline insulin-like growth factor (IGF)-1, IGF-binding proteins (BPs), or angiogenic markers (vascular endothelial growth factor \[VEGF\] and interleukin \[IL\]-8) plasma levels or their pre- and post-treatment plasma level changes, significantly differ between progressor and non-progressor patients and correlate them with survival.

III. To assess whether the baseline protein kinase B (AKT) and/or mitogen-activated protein kinase 1 (ERK) phosphorylation or the extent of inhibition of AKT and/or ERK phosphorylation in peripheral blood mononuclear cells (PBMCs) significantly differs between progressors and non-progressors and to correlate them with survival.

IV. To determine whether the subcellular localization of IGF-1R, IGF-BPs, and/or the phosphorylation of IGF-1R throughout the cell by AQUA (automated quantitative immunofluorescence) significantly differs between progressors and non-progressors and correlate them with survival.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive linsitinib orally (PO) twice daily (BID) on days 1-21.

ARM II: Patients receive topotecan hydrochloride intravenously (IV) over 30 minutes or PO once daily (QD) on days 1-5. Patients may crossover to Arm I at the time of progressive disease.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks and then every 6 months for 2 years.

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