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Tailored Second Line Treatment by Epidermal Growth Factor Receptor (EGFR) Mutation in Patients With Advanced Lung Adenocarcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00903292
Recruitment Status : Unknown
Verified May 2009 by National Cheng-Kung University Hospital.
Recruitment status was:  Recruiting
First Posted : May 18, 2009
Last Update Posted : May 18, 2009
Information provided by:
National Cheng-Kung University Hospital

Brief Summary:
Currently the investigators have two different classes of second-line treatment options in recurrent non-small Cell Lung Cancer (NSCLC). In chemotherapy, docetaxel and pemetrexed produced similar treatment efficacy outcomes, while pemetrexed had a better tolerability. In recent analysis of pemetrexed clinical studies, a strong treatment-by-histology interaction in overall survival and progression free survival that indicated better efficacy for non-squamous patients treated with pemetrexed. These data supports that pemetrexed could be a preferable chemotherapy drug especially in adenocarcinoma NSCLC patients.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: erlotinib (Tarceva) Drug: pemetrexed (Alimta) Not Applicable

Detailed Description:

On the other hand, EGFR TKI (gefitinib or erlotinib) both produced somewhat similar higher response rate (around 25%) in general Taiwan adenocarcinoma NSCLC patients, while the median overall survival time didn't longer than chemotherapy treated patients. A recent prospective study of gefitinib in chemonaive adenocarcinoma NSCLC patients showed that the objective response rate was lower to be only 1.1% among EGFR mutation negative patients.

Since typical EGFR gene mutations (i.e., the deletion of typically five amino acids at codons 746-750 (ELREA) in exon 19 and a leucine-to-arginine mutation at codon 858 (L858R)) are a good predictor for tumor response to tyrosine kinase inhibitor, this present study is to tailor the patient's treatment according to his/her EGFR gene mutation status. Receptor tyrosine kinase inhibitor (erlotinib in this study) will be the suggested second-line drug of recommendation for typical EGFR gene mutation patients, and chemotherapy (pemetrexed in this study) will be the suggested second-line drug of recommendation for EGFR wild type patients.

The aim of this study is to increase the overall tumor response rate to 40% from current treatment outcome (around 25%) by this tailored second line treatment. The further interests of this study include prospectively evaluate the predictivity of EGFR gene mutation to tumor response.

The primary objective of this study is to determine the overall tumor response rate of tailored second line treatment determined by typical EGFR gene mutation in patients with advanced lung adenocarcinoma.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Tailored Second Line Treatment by EGFR Mutation in Patients With Advanced Lung Adenocarcinoma
Study Start Date : March 2009
Estimated Primary Completion Date : April 2010
Estimated Study Completion Date : December 2010

Arm Intervention/treatment
Active Comparator: A, erlotinib
If EGFR mutation found then assigned to thyrosine kinase inhibitor (erlotinib)
Drug: erlotinib (Tarceva)
chemotherapy with erlotinib

Active Comparator: B, pemetrexed
If EGFR wild type found then assigned to chemotherapy (pemetrexed)
Drug: pemetrexed (Alimta)
Chemotherapy with pemetrexed

Primary Outcome Measures :
  1. The primary analysis will be the overall best response rate, including a 95% confidence interval (Leemis and Trivedi 1996). [ Time Frame: 02/2009 - 04/2010 ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologic diagnosis of adenocarcinoma of NSCLC.
  • Locally advanced or metastatic disease (stage IIIB or IV), defined by the American Joint Committee on Cancer Staging Criteria for NSCLC (Fleming et al. 1997; Mountain 1997)
  • Patients must have previously received one chemotherapy regimen for palliative therapy of locally advanced or metastatic disease.

    • NOTE: First-line therapy with a tyrosine kinase inhibitor alone or regimens including pemetrexed, docetaxel, cetuximab, and trastuzumab is not allowed for enrollment in this study.
    • Prior chemotherapy for earlier stage disease is allowed, but only a single regimen is allowed for prior palliative therapy of locally advanced or metastatic disease.
  • Prior chemotherapy must be completed at least 2 weeks prior to study enrollment and the patient must have recovered from the acute toxic effects of the treatment.
  • Disease status must be that of measurable disease as defined by RECIST criteria (Therasse et al. 2000).
  • Performance status of 0 to 2 on the ECOG Scale (See Protocol Attachment 2.).
  • Estimated life expectancy of at least 8 weeks.
  • Adequate organ function including the following:

    • Bone marrow: absolute neutrophil count (ANC) 1.5* 109/L, platelets 100*109/L, hemoglobin 9 g/dL.
    • Hepatic: bilirubin 1.5ULN, AST and ALT 2.5 ULN (AST, ALT 5 ULN is acceptable if liver has tumor involvement).
    • Renal: serum creatine 1.5 ULN; Calculated creatinine clearance 45 mL/min (using the standard Cockcroft-Gault formula; Cockcroft and Gault 1976).
  • For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test and must not be lactating.
  • For men: Must be surgically sterile, or compliant with a contraceptive regimen during and for 6 months after the treatment period.
  • Men or women of at least 20 years of age, and signed informed consent from the patient.

Exclusion Criteria:

  • Subject has untreated brain or meningeal metastases.

    • CT scans are not required to rule out brain or meningeal metastases unless there is a clinical suspicion of central nervous system disease).
    • Subjects with treated brain metastases that are radiographically or clinically stable for at least 2 weeks after therapy and have no evidence of cavitation or hemorrhage in the brain lesion are eligible providing that they are asymptomatic.
  • Have previously completed or withdrawn from this study, or received pemetrexed, thymidylate synthetase or dihydrofolate reductase previously outside this study.
  • Concurrent administration of any other tumor therapy.
  • Active infection (at the discretion of the investigator).
  • History of significant neurological or mental disorder, including seizures or dementia.
  • Second primary malignancy that is clinically detectable within 5 years of consideration for study enrollment.
  • Have received treatment within the last 30 days with a drug that has not received regulatory approval (e.g., warfarin or Coumadin) for any indication at the time of study entry.
  • Inability to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) 2 days before, the day of, and 2 days after the dose of pemetrexed.

    • If a patient is taking an NSAID (Cox-2 inhibitors included) or salicylate with a long half-life (e.g., naproxen, piroxicam, diflunisal, nabumetone, rofecoxib, or celecoxib) it should not be taken 5 days before, the day of, and 2 days after the dose of pemetrexed.
  • Inability or unwillingness to take erlotinib, folic acid, vitamin B12 supplementation, or dexamethasone.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00903292

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Contact: Wu-Chou Su, PHD 886-6-2353535 ext 4289

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National Cheng-Kung University Hospital Recruiting
Tainan, Taiwan, 704
Contact: Hui-Shu Yang, Bachelor    +886-6-2353535 ext 4289   
Sponsors and Collaborators
National Cheng-Kung University Hospital
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Principal Investigator: Wu-Chou Su, PhD National Cheng-Kung University Hospital
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Responsible Party: Wu- Chou Su, National Cheng-Kung University Hospital Identifier: NCT00903292    
Other Study ID Numbers: HR98004
First Posted: May 18, 2009    Key Record Dates
Last Update Posted: May 18, 2009
Last Verified: May 2009
Keywords provided by National Cheng-Kung University Hospital:
EGFR mutation rate
Additional relevant MeSH terms:
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Adenocarcinoma of Lung
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Erlotinib Hydrochloride
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Protein Kinase Inhibitors