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Recurrent Small Cell Lung CarcinomaPhase 2NCT01533181

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

A Phase 2 study testing Laboratory Biomarker Analysis, Linsitinib and Pharmacological Study in people with Recurrent Small Cell Lung Carcinoma, run by National Cancer Institute (NCI) at 11 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Small Cell Lung Carcinoma
What is being tested?
Laboratory Biomarker Analysis, Linsitinib and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
11 sitesin 2 countries
Study dates
Feb 2012to Nov 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

11 sites in 2 countries.

11 sites in 2 countries

United States10 sites

  • Emory University/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital

    Baltimore, Maryland, 21231

  • Billings Clinic Cancer Center

    Billings, Montana, 59107

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

Singapore1 site

  • Johns Hopkins Singapore

    Singapore, 308433

Other trials in Singapore

About this study

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)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Laboratory Biomarker Analysis, Linsitinib, Pharmacological Study, Topotecan Hydrochloride
Medical subject headings
Small Cell Lung Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LinsitinibDrug

    Also called IGF-1R inhibitor OSI-906, OSI-906, OSI-906AA

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

  • Pharmacological StudyOther

    Correlative studies

  • Topotecan HydrochlorideDrug

    Also called Hycamptamine, Hycamtin, SKF S-104864-A, Topotecan HCl

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

Study groups in NCT01533181
Study groupRoleWhat they receive
Arm I: OS-906 (linsitinib)ExperimentalOS-906 daily, continuously, every 3 weeks.
Receives: Other: Laboratory Biomarker Analysis; Drug: Linsitinib; Other: Pharmacological Study
Arm II (topotecan hydrochloride)Active comparatorPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Topotecan Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 6 months

Secondary outcomes (3)

  1. Disease Control Rate (DCR)

    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.

    Measured: Up to 2 years

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

    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.

    Measured: 1 year, 6 months

  3. Overall Survival (OS)

    OS: Time from study enrollment to death from any cause. OS summarized similarly to PFS utilizing the K-M method.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2012 (estimated)
  2. Study startFeb 2012
  3. Primary completionNov 2014
  4. Study completionNov 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01533181
Sponsor's protocol ID
NCI-2012-00245
Other IDs
NCI-2012-00245, CDR0000724806, MCC-16628, MCC 16628, 8873, N01CM00070, N01CM00099, N01CM00100
Status last verified
Aug 2015
First submitted
11 Feb 2012
Last updated
14 Jan 2016
Data monitoring committee
No

Publications

  • 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.

    PubMed 27694157

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis, Linsitinib and Pharmacological Study in people with Recurrent Small Cell Lung Carcinoma, run by National Cancer Institute (NCI) at 11 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median Progression Free Survival (PFS) (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01533181, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2016.

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