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Phase II Randomized Study of Enzastaurin Hydrochloride in Preventing Non-Small Cell Lung Cancer in Former Smokers
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Trial Contact Information Registry Information
Alternate Title
Enzastaurin in Preventing Non-Small Cell Lung Cancer in Former Smokers
Basic Trial Information
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Protocol IDs
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Phase II
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Biomarker/Laboratory analysis, Prevention
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Active
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45 and over
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NCI, Pharmaceutical / Industry
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MCC-14787 MCC-104545, LILLY-H6Q-MC-S009A, U01-CA-101222, NCT00387816
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Objectives Primary - Compare the difference between the average Ki-67 LI (percentage of cells positively labeled with Ki-67, a marker of cellular proliferation) in all bronchial biopsy specimens of former smokers before and after treatment with enzastaurin hydrochloride vs placebo.
Secondary - Compare the adverse events in patients treated with these regimens.
Tertiary - Assess target inhibition in patients treated with these regimens.
- Assess target inhibition of GSK3β in patients treated with these regimens.
- Assess MCM2, cleaved caspase 3, pPKCβ, and pGSK3β by immunohistochemistry in patients treated with these regimens.
- Measure metaplasia/dysplasia by light microscopy in samples from patients treated with these regimens.
- Assess fractional allele loss by single nucleotide polymorphism chip arrays in samples from patients treated with these regimens.
- Assess cytokine response profiles by western analysis for pStat3 and pErk1/2 of short-term cultures after exposure to epidermal growth factor and interleukin-6 in samples from patients treated with these regimens.
Entry Criteria Disease Characteristics:
- History of cigarette smoking ≥ 30 pack years
- Quit smoking ≥ 1 year prior to study entry
- Must be willing to abstain from smoking and avoid second-hand smoke exposure
- Negative cotinine by urine dipstick
- Cytologically confirmed sputum atypia in an induced sputum specimen collected on site
- Metaplasia or dysplasia on at least one bronchoscopy specimen
- No evidence of lung cancer or carcinoma in situ by sputum cytology, helical CT scan, or bronchoscopy
- Patients with history of stage IA or IB non-small cell lung cancer allowed provided all of the following criteria are met:
- Completely resected ≥ 12 months ago
- No evidence of recurrence
- At least 1 mediastinal lymph node station negative for cancer
- No history of small cell lung cancer
Prior/Concurrent Therapy:
- No prior anticancer chemotherapy or hormonal therapy
- More than 5 years since prior radiotherapy to the chest
- More than 6 months since prior major surgery
- More than 6 months since prior cardiac surgery or percutaneous transluminal coronary angioplasty
- At least 6 months since prior chemoprevention trial
- No concurrent participation in another chemoprevention trial
- At least 14 days since prior and no concurrent enzyme-inducing antiepileptic drugs
- More than 30 days since prior and no concurrent investigational agents
- No concurrent illicit drug or ethanol abuse
- No other concurrent anticancer therapy, immunotherapy, hormonal therapy, or curative radiotherapy
Patient Characteristics:
- ECOG performance status 0-1
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9 g/dL
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 1.5 times ULN
- ALT and AST ≤ 1.5 times ULN
- Creatinine < 1.5 mg/dL
- Able to undergo bronchoscopy and helical CT scanning of the chest
- Able to swallow tablets
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No known coagulopathy (INR > 1.5, PT > 37.0 sec)
- No history of malignancy within the past 5 years, except for any of the following:
- Nonmelanoma skin cancer
- Cervical carcinoma in situ
- No active pulmonary infection
- No sarcoidosis
- No connective tissue disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, scleroderma, sclerosing cholangitis, or Wegener’s granulomatosis)
- No chronic obstructive pulmonary disease, asthma, or sleep apnea requiring inhaled steroids, bronchodilators, or oxygen
- No cerebrovascular accident or transient ischemic attack within the past 6 months
- No active coronary artery disease
- No ECG abnormalities indicative of cardiac disease
- No active peptic ulcer disease
- No mental illness that would preclude study participation
- No investigator site personnel directly affiliated with study and/or their immediate families
- Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted
- Not an employee at Eli Lilly and Company
Expected Enrollment 186 A total of 186 patients will be accrued for this study. Outcomes Primary Outcome(s)Difference between average Ki-67 LI (percentage of cells positively labeled with Ki-67) before and after completion of treatment
Secondary Outcome(s)Target inhibition Target inhibition of GSK3β Biomarkers MCM2, cleaved caspase 3, pPKCβ, and pGSK3β as assessed by immunohistochemistry Metaplasia or dysplasia as assessed by light microscopy Fractional allele loss as assessed by single nucleotide polymorphism chip arrays Cytokine response profiles as measured by western analysis
Outline This is a randomized, placebo-controlled, double-blind study. Patients are stratified according to history of stage I non-small cell lung cancer (yes vs no), evidence of airway obstruction (FEV1/FVC ≤ 0.7 vs > 0.7), and pretreatment bronchial biopsy histology (presence vs absence of dysplasia). Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive oral enzastaurin hydrochloride once daily for 6 months in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive oral placebo once daily for 6 months in the absence of disease progression or unacceptable toxicity.
In both arms, all patients undergo blood collection and bronchoscopy with brushings and biopsies after completion of treatment. Laboratory studies are conducted on tissue and blood samples to measure biological markers, including Ki-67, PKCβ2, GSK3β, and MCM2, and to assess apoptosis, morphology, cytokine response profiles, and genetic alterations by immunohistochemistry and western analysis. After completion of study treatment, patients are followed at 12 and 24 months.
Trial Contact Information
Trial Lead Organizations H. Lee Moffitt Cancer Center and Research Institute at University of South Florida | | | Gerold Bepler, MD, PhD, Principal investigator | | | | Trial Sites
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U.S.A. |
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Florida |
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Tampa |
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| | | | | | | | H. Lee Moffitt Cancer Center and Research Institute at University of South Florida |
| | Clinical Trials Office - H. Lee Moffitt Cancer Center and Reseach Institute | |
| Email:
canceranswers@moffitt.org |
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Registry Information | | Official Title | | A Phase IIB Randomized, Placebo-Controlled, Double-Blind Study of Enzastaurin HCL (LY317615) for Lung Cancer Prevention in Former Smokers | | Trial Start Date | | 2007-10-15 | | Trial Completion Date | | 2008-10-15 (estimated) | | Registered in ClinicalTrials.gov | | NCT00387816 | | Date Submitted to PDQ | | 2006-09-14 | | Information Last Verified | | 2008-04-20 | | NCI Grant/Contract Number | | CA101222, CA76292 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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