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

NCT01533181 | Completed Phase 2 Results

• 9 other identifiers: NCI-2012-00245CDR0000724806MCC-16628MCC 166288873N01CM00070N01CM00099N01CM00100P30CA076292
• Study Type: interventional
• Target: 44
• Locations: 2 countries
• Sites: 11

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.

Conditions

Recurrent Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (1)

• Median Progression Free Survival (PFS)

  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.

  Up to 6 months

Secondary Outcomes (3)

• Disease Control Rate (DCR)

  Up to 2 years

• Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs

  1 year, 6 months

• Overall Survival (OS)

  Up to 2 years

Other Outcomes (1)

• Changes in Biomarker Expression

  Baseline to up to day 1 of course 3

Study Arms (2)

Arm I: OS-906 (linsitinib)

EXPERIMENTAL

OS-906 daily, continuously, every 3 weeks.

Other: Laboratory Biomarker Analysis; Drug: Linsitinib; Other: Pharmacological Study

Arm II (topotecan hydrochloride)

ACTIVE COMPARATOR

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; Other: Pharmacological Study; Drug: Topotecan Hydrochloride

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I: OS-906 (linsitinib); Arm II (topotecan hydrochloride)

Linsitinib DRUG

150 mg given orally (PO) twice a day (BID)

Also known as: IGF-1R inhibitor OSI-906, OSI-906, OSI-906AA

Arm I: OS-906 (linsitinib)

Pharmacological Study OTHER

Correlative studies

Arm I: OS-906 (linsitinib); Arm II (topotecan hydrochloride)

Topotecan Hydrochloride DRUG

1.5 mg/m\^2 intravenously (IV) or 2.3 mg/m\^2 orally (PO)

Also known as: Hycamptamine, Hycamtin, SKF S-104864-A, Topotecan HCl, topotecan hydrochloride (oral)

Arm II (topotecan hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (11)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

Billings Clinic Cancer Center

Billings, Montana, 59107, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Johns Hopkins Singapore

Singapore, 308433, Singapore

Location

Related Publications (1)

• Chiappori AA, Otterson GA, Dowlati A, Traynor AM, Horn L, Owonikoko TK, Ross HJ, Hann CL, Abu Hejleh T, Nieva J, Zhao X, Schell M, Sullivan DM. A Randomized Phase II Study of Linsitinib (OSI-906) Versus Topotecan in Patients With Relapsed Small-Cell Lung Cancer. Oncologist. 2016 Oct;21(10):1163-1164. doi: 10.1634/theoncologist.2016-0220. Epub 2016 Sep 30.

  PMID: 27694157 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol; Topotecan

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Alberto Chiappori
• Organization: H. Lee Moffitt Cancer Center and Research Institute

alberto.chiappori@moffitt.org

813-745-2158

Study Officials

• Alberto Chiappori

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2012
• First Posted: February 15, 2012
• Study Start: February 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: January 14, 2016
• Results First Posted: January 14, 2016

Record last verified: 2015-08

Locations

SG (1); US (10)