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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01533181
First received: February 11, 2012
Last updated: October 2, 2014
Last verified: July 2014
  Purpose

This randomized phase II trial studies how well linsitinib or topotecan hydrochloride works in treating patients with relapsed small cell lung cancer. Linsitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether linsitinib is more effective than topotecan hydrochloride in treating small cell lung cancer.


Condition Intervention Phase
Recurrent Small Cell Lung Cancer
Drug: linsitinib
Drug: topotecan hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, 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)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • PFS [ Time Frame: From the time of randomization to time of disease progression or death, assessed up to 18 weeks ] [ Designated as safety issue: No ]
    PFS will be 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 will be constructed when appropriate.


Secondary Outcome Measures:
  • RR assessed by Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Will be summarized using both point estimates and exact confidence intervals based on the binomial distribution by arm.

  • DCR (complete response + partial response + stable disease) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Will be summarized using both point estimates and exact confidence intervals based on the binomial distribution by arm.

  • OS [ Time Frame: From study enrollment to death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    Will be summarized similarly to PFS utilizing the K-M method.

  • Incidence of toxicities as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Simple descriptive statistics will be utilized.


Other Outcome Measures:
  • Changes in biomarker expression [ Time Frame: Baseline to up to day 1 of course 3 ] [ Designated as safety issue: No ]
    Will be assessed by the Wilcoxon rank sum test.


Estimated Enrollment: 95
Study Start Date: February 2012
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (linsitinib)
Patients receive linsitinib PO BID on days 1-21.
Drug: linsitinib
Given PO
Other Name: OSI-906
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Active Comparator: Arm II (topotecan hydrochloride)
Patients receive topotecan hydrochloride IV over 30 minutes or PO QD on days 1-5.
Drug: topotecan hydrochloride
Given IV or PO
Other Names:
  • hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • TOPO
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

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.* NOTE: *Patients treated on arm II 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01533181

Locations
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 Hospitals and Clinics
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
Billings, Montana, United States, 59107-7000
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Singapore
Johns Hopkins Singapore International Medical Centre
Singapore, Singapore, 308433
Sponsors and Collaborators
Investigators
Principal Investigator: Alberto Chiappori Moffitt Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01533181     History of Changes
Obsolete Identifiers: NCT01387386
Other Study ID Numbers: NCI-2012-00245, NCI-2012-00245, CDR0000724806, MCC-16628, MCC 16628, 8873, N01CM00100, N01CM00070, N01CM00099, P30CA076292
Study First Received: February 11, 2012
Last Updated: October 2, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 20, 2014