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)
18 Years
N/A
Both
Combined Type Small Cell Lung Cancer, Fusiform Type Small Cell Lung Cancer, Lymphocyte-like Type Small Cell Lung Cancer, Polygonal Type Small Cell Lung Cancer, Recurrent Small Cell Lung Cancer
Trial Information
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)
PRIMARY OBJECTIVES:
I. To compare the progression-free survival (PFS) of single-agent linsitinib (OSI-906) to
that of single-agent topotecan hydrochloride (topotecan) 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 using Response Evaluation Criteria in
Solid Tumors (RECIST) v 1.1.
II. To describe the toxicity profile of single-agent OSI-906 in this population using the
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
v.4.0.
III. To evaluate potential predictive biomarkers of OSI-906 sensitivity by examining
multiple biomarkers (molecular and radiographic) and to correlate their pre- and
post-treatment samples with clinical outcomes (RR, DCR, PFS, and OS). (Exploratory) IV. To
determine whether the baseline IGF-1, IGF-BP's, or angiogenic markers (VEGF and 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. (Exploratory) V. To
assess whether the baseline AKT and/or ERK phosphorylation or the extent of inhibition of
AKT and/or ERK phosphorylation in peripheral blood mononuclear cells (PBMC) significantly
differs between progressors and non-progressors and to correlate them with survival.
(Exploratory) VI. 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. (Exploratory)
OUTLINE: This is a multicenter study. Patients are stratified according to response to prior
first-line platinum therapy (platinum sensitive vs platinum resistant) and ECOG performance
status (0-1 vs 2). 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 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. Patients undergo blood sample collection at baseline, at 6 weeks of
treatment, and at the time of disease progression for IGF-1, IGF-BP's, VEGF, IL-8, Akt,
and/or ERK phosphorylation analysis by ELISA and AQUA. Patients undergo enhanced thoracic
computed tomography scans at baseline, at 6 weeks of treatment, and at the time of
progression for radiomic analysis.
After completion of study treatment, patients are followed up for 4 weeks and then every 6
months for 2 years.
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed small cell lung cancer
(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 (either with etoposide or irinotecan)
- 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
- 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
- Available archival tumor tissue is NOT mandatory for enrollment (will be requested)
- Life expectancy of greater than 6 weeks
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2; (Karnofsky ≥
60%)
- Leukocytes (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 glutamic 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
- Fasting blood glucose < 160 mg/dL at baseline
- 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
- WOCBP must provide a negative pregnancy test (serum or urine) within 14 days prior to
registration
- Patients must have the ability to understand and the willingness to sign a written
informed consent document
- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to OSI-906 or other agents used in the study (topotecan)
- No 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
- Patients in the following scenarios are excluded:
- 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
- See Disease Characteristics
- 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)
- No 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
- No patients who are receiving any other investigational agents
- Potent CYP1A2 inhibitors (ciprofloxacin and fluvoxamine) are prohibited
- Concomitant use of glycoprotein inhibitors with topotecan capsules is not allowed
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Outcome Measure:
Progression-free survival
Outcome Description:
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.
Outcome Time Frame:
Time from the time of randomization to time of disease progression or death, up to 18 weeks
Safety Issue:
No
Principal Investigator
Alberto Chiappori
Investigator Role:
Principal Investigator
Investigator Affiliation:
H. Lee Moffitt Cancer Center and Research Institute
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-00245
NCT ID:
NCT01533181
Start Date:
February 2012
Completion Date:
Related Keywords:
- Combined Type Small Cell Lung Cancer
- Fusiform Type Small Cell Lung Cancer
- Lymphocyte-like Type Small Cell Lung Cancer
- Polygonal Type Small Cell Lung Cancer
- Recurrent Small Cell Lung Cancer
- Lung Neoplasms
- Small Cell Lung Carcinoma
Name | Location |
|---|---|
| H. Lee Moffitt Cancer Center and Research Institute | Tampa, Florida 33612 |
| University of Wisconsin Hospital and Clinics | Madison, Wisconsin 53792-0001 |
| Mayo Clinic in Arizona | Scottsdale, Arizona 85259-5404 |
| Vanderbilt University | Nashville, Tennessee 37232-6305 |
| University of North Carolina | Chapel Hill, North Carolina 27599 |
| Case Western Reserve University | Cleveland, Ohio 44106 |
| Emory University | Atlanta, Georgia 30322 |
| Ohio State University Medical Center | Columbus, Ohio 43210 |
| University of Chicago Comprehensive Cancer Center | Chicago, Illinois 60637-1470 |
| Billings Clinic | Billings, Montana 59107-7000 |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital | Baltimore, Maryland 21231 |
