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Tailored Second Line Treatment by EGFR Mutation in Patients With Advanced Lung Adenocarcinoma

20 Years
80 Years
Open (Enrolling)
Non-Small Cell Lung Cancer

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Trial Information

Tailored Second Line Treatment by EGFR Mutation in Patients With Advanced Lung Adenocarcinoma

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

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

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.

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

- 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

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

- 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

- 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.

Type of Study:


Study Design:

Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Screening

Outcome Measure:

The primary analysis will be the overall best response rate, including a 95% confidence interval (Leemis and Trivedi 1996).

Outcome Time Frame:

02/2009 - 04/2010

Safety Issue:


Principal Investigator

Wu-Chou Su, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cheng-Kung University Hospital


Taiwan: Department of Health

Study ID:




Start Date:

March 2009

Completion Date:

December 2010

Related Keywords:

  • Non-Small Cell Lung Cancer
  • EGFR
  • EGFR mutation rate
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms