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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01533181
Recruitment Status : Completed
First Posted : February 15, 2012
Results First Posted : January 14, 2016
Last Update Posted : January 14, 2016
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief 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.

Condition or disease Intervention/treatment Phase
Recurrent Small Cell Lung Carcinoma Other: Laboratory Biomarker Analysis Drug: Linsitinib Other: Pharmacological Study Drug: Topotecan Hydrochloride Phase 2

Detailed Description:


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).


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.


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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of Single Agent OSI-906, an Oral, Small Molecule, Tyrosine Kinase Inhibitor (TKI) of the Insulin Growth Factor-1 Receptor (IGF-1R) Versus Topotecan for the Treatment of Patients With Relapsed Small Cell Lung Cancer (SCLC)
Study Start Date : February 2012
Actual Primary Completion Date : November 2014
Actual Study Completion Date : November 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Arm I: OS-906 (linsitinib)
OS-906 daily, continuously, every 3 weeks.
Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Linsitinib
150 mg given orally (PO) twice a day (BID)
Other Names:
  • IGF-1R inhibitor OSI-906
  • OSI-906
  • OSI-906AA

Other: Pharmacological Study
Correlative studies

Active Comparator: Arm II (topotecan hydrochloride)
Patients receive topotecan hydrochloride IV over 30 minutes or PO QD on days 1-5. Patients may crossover to Arm I at the time of progressive disease.
Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Drug: Topotecan Hydrochloride
1.5 mg/m^2 intravenously (IV) or 2.3 mg/m^2 orally (PO)
Other Names:
  • Hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • Topotecan HCl
  • topotecan hydrochloride (oral)

Primary Outcome Measures :
  1. Median Progression Free Survival (PFS) [ Time Frame: Up to 6 months ]
    PFS: Time from randomization to time of disease progression or death. PFS summarized with the Kaplan-Meier (K-M) method by two arms (experimental versus control). Confidence intervals for the median PFS and PFS rates at different time points to be constructed when appropriate.

Secondary Outcome Measures :
  1. Disease Control Rate (DCR) [ Time Frame: Up to 2 years ]
    DCR: Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) + Progressive Disease (PD). DCR summarized using both point estimates and exact confidence intervals based on the binomial distribution by arm.

  2. Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs [ Time Frame: 1 year, 6 months ]
    Participants with Grade 3 and 4 toxicities, possibly/probably/definitely related to study drugs. Number of Participants is per Event Category. Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

  3. Overall Survival (OS) [ Time Frame: Up to 2 years ]
    OS: Time from study enrollment to death from any cause. OS summarized similarly to PFS utilizing the K-M method.

Other Outcome Measures:
  1. Changes in Biomarker Expression [ Time Frame: Baseline to up to day 1 of course 3 ]
    To be assessed by the Wilcoxon rank sum test.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01533181

United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States, 52242
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
Baltimore, Maryland, United States, 21231
United States, Montana
Billings Clinic Cancer Center
Billings, Montana, United States, 59107
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
United States, Tennessee
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Johns Hopkins Singapore
Singapore, Singapore, 308433
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Alberto Chiappori Moffitt Cancer Center

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI) Identifier: NCT01533181     History of Changes
Obsolete Identifiers: NCT01387386
Other Study ID Numbers: NCI-2012-00245
NCI-2012-00245 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MCC 16628 ( Other Identifier: Moffitt Cancer Center )
8873 ( Other Identifier: CTEP )
N01CM00070 ( U.S. NIH Grant/Contract )
N01CM00099 ( U.S. NIH Grant/Contract )
N01CM00100 ( U.S. NIH Grant/Contract )
P30CA076292 ( U.S. NIH Grant/Contract )
First Posted: February 15, 2012    Key Record Dates
Results First Posted: January 14, 2016
Last Update Posted: January 14, 2016
Last Verified: August 2015

Additional relevant MeSH terms:
Small Cell Lung Carcinoma
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents