Expired Study
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Baltimore, Maryland 21231


Purpose:

RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer. It may also help doctors learn how well patients will respond to treatment. PURPOSE: This phase II trial is studying how well a laboratory test predicts response to erlotinib in patients with metastatic or unresectable non-small cell lung cancer that did not respond to previous treatment.


Study summary:

OBJECTIVES: Primary - Determine whether the extent of inhibition of ERK phosphorylation in lung cancer cells exposed ex vivo and in vivo to erlotinib hydrochloride significantly differs between responding and nonresponding patients with relapsed, metastatic or unresectable non-small cell lung cancer. Secondary - Determine whether the extent of inhibition of epidermal growth factor receptor (EGFR) and AKT phosphorylation in lung cancer cells exposed ex vivo and in vivo to erlotinib hydrochloride significantly differs between these 2 groups of patients. - Correlate the extent of inhibition of EGFR, ERK, and AKT phosphorylation in lung cancer cells exposed ex vivo with erlotinib hydrochloride with in vivo objective tumor response to erlotinib hydrochloride in these patients. - Correlate EGFR gene mutation and amplification status with pharmacodynamic evidence of response to erlotinib hydrochloride in these patients. OUTLINE: This is an open-label, pilot study. Patients receive oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients undergo tumor fine-needle aspiration biopsies under ultrasound or CT scan guidance at baseline and between days 12-15 for laboratory studies. Laboratory studies include quantitative western blot and enzyme-linked immunosorbent assays, gene mutation and amplification, and ex vivo assays. Tumor cells are also analyzed for changes in phosphorylation status and/or expression levels of pharmacodynamic markers, including total- and phospho-epidermal growth factor receptor, total- and phospho-ERK, and total- and phospho-AKT. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.


Criteria:

DISEASE CHARACTERISTICS: - Histologically or cytologically confirmed metastatic or unresectable non-small cell lung cancer - Relapsed disease - Failed ≥ 1 prior chemotherapy regimen - Measurable disease - Tumor must be accessible to fine-needle aspiration - No uncontrolled brain metastases - Patients with brain metastases must have stable neurologic status after local therapy (surgery or radiotherapy) for ≥ 4 weeks and no neurologic dysfunction that would preclude evaluation of neurologic and other adverse events PATIENT CHARACTERISTICS: - ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% - Life expectancy > 12 weeks - WBC > 3,000/mm³ - Absolute neutrophil count > 1,500/mm³ - Platelet count > 100,000/mm³ - Bilirubin normal - PT and activated PTT normal - Creatinine normal OR creatinine clearance > 60 mL/min - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - No uncontrolled intercurrent illness, including, but not limited to, any of the following: - Ongoing or active infection - Symptomatic congestive heart failure - Unstable angina pectoris - Cardiac arrhythmia - Psychiatric illness or social situation that would preclude study compliance - No significant ophthalmologic abnormalities*, including any of the following: - Severe dry eye syndrome - Keratoconjunctivitis sicca - Sjögren's syndrome - Severe exposure keratopathy - Disorders that might increase the risk for epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis) - No serious, nonhealing wound, ulcer, or bone fracture - No significant traumatic injury within the past 14 days NOTE: *Patients with mild forms of any of the above ophthalmologic abnormalities, an asymptomatic history, or a normal ophthalmologic examination allowed at the discretion of the investigator. Patients with treatable conditions (e.g., infectious keratitis/conjunctivitis or allergic conjunctivitis) allowed after treatment or resolution of the condition. PRIOR CONCURRENT THERAPY: - See Disease Characteristics - No prior small molecule inhibitors of epidermal growth factor receptor, including erlotinib hydrochloride or gefitinib - At least 4 weeks since prior anticancer therapy, including chemotherapy, radiotherapy, biologic therapy, or other investigational therapy (6 weeks for nitrosoureas or mitomycin C) - More than 14 days since prior major surgery or open biopsy and recovered - At least 7 days since prior and no concurrent inhibitors of CYP3A4, including any of the following: - Itraconazole - Herbal extracts and tinctures, including any of the following: - Hydrastis canadensis (goldenseal) - Uncaria tomentosa (cat's claw) - Echinacea angustifolia roots - Trifolium pratense (wild cherry) - Chamomile - Licorice root - Dillapiol - Naringenin - No concurrent inducers of CYP3A4, including any of the following: - Phenytoin - Carbamazepine - Rifampin - Barbiturates - Hypericum perforatum (St. John's wort) - No concurrent chemotherapy - No other concurrent investigational agents - No concurrent combination antiretroviral therapy for HIV-positive patients - No concurrent radiotherapy, including palliative radiotherapy - No concurrent therapeutic anticoagulation - No other concurrent anticancer agents or therapies


Study is Available At:


Original ID:

JHOC-J0655, CDR0000512886


NCT ID:

NCT00673569


Secondary ID:

P30CA006973


Study Acronym:


Brief Title:

Laboratory Test in Predicting Response to Erlotinib in Patients With Relapsed Metastatic or Unresectable Non-Small Cell Lung Cancer That Did Not Respo


Official Title:

A Phase II Single-Arm Trial Assessing the Use of an Ex Vivo Sensitivity Assay to Predict Response of Relapsed Metastatic Non-Small Cell Lung Cancer Patients to Erlotinib


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Sidney Kimmel Comprehensive Cancer Center


Oversight Authority:

United States: Federal Government


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Masking: Open Label, Primary Purpose: Treatment


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

40


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Charles M. Rudin, MD, PhD
Principal Investigator
Sidney Kimmel Comprehensive Cancer Center

Study Dates

Start Date:September 2006
Primary Completion Date:July 2007
Primary Completion Type:Actual
Verification Date:August 2010
Last Changed Date:August 5, 2010
First Received Date:May 6, 2008

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Proportion of patients with EGFR gene amplification and gene mutation with an ex vivo response and clinical response
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Comparison of ex vivo and in vivo effects of erlotinib hydrochloride
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Frequency and proportion of patients with complete response, partial response, stable disease, and progressive disease
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Toxicity
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Extent of inhibition of epidermal growth factor receptor (EGFR) and AKT phosphorylation by erlotinib hydrochloride
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Clinical response
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Extent of inhibition of ERK phosphorylation by erlotinib hydrochloride
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Quantitative assessment of phospho-ERK
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:erlotinib hydrochloride
Intervention Type:Genetic
Name:gene expression analysis
Intervention Type:Genetic
Name:protein expression analysis
Intervention Type:Other
Name:immunoenzyme technique
Intervention Type:Other
Name:immunologic technique
Intervention Type:Other
Name:laboratory biomarker analysis
Intervention Type:Procedure
Name:needle biopsy

Study Arms

There are no available Study Arms

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Sidney Kimmel Comprehensive Cancer Center
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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