Study of Blood and Tissue Samples in Predicting Response to Second-Line Therapy Using Erlotinib Hydrochloride or Chemotherapy in Patients With Advanced Non-Small Cell Lung Cancer
Lung Cancer
Conditions: official terms
Carcinoma, Non-Small-Cell Lung - Lung Neoplasms
Conditions: Keywords
recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer
Study Type
Study Phase
Phase 3
Study Design
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Name: docetaxel Type: Drug
Name: erlotinib hydrochloride Type: Drug
Name: pemetrexed disodium Type: Drug
Name: fluorescence in situ hybridization Type: Genetic
Name: mutation analysis Type: Genetic
Name: proteomic profiling Type: Genetic
Name: immunohistochemistry staining method Type: Other
Name: laboratory biomarker analysis Type: Other
Name: matrix-assisted laser desorption/ionization time of flight mass spectrometry Type: Other
Name: breath test Type: Procedure
Overall Status
RATIONALE: Studying the proteins expressed in samples of blood and tissue from patients with cancer may help doctors identify biomarkers related to cancer. It may also help doctors predict how patients will respond to treatment.

PURPOSE: This randomized phase III trial is studying blood and tissue samples in predicting response to second-line therapy using erlotinib hydrochloride or chemotherapy in patients with advanced non-small cell lung cancer.
Detailed Description

- To evaluate the predictive value of proteomic profiling on the effect of second-line therapy with erlotinib hydrochloride vs standard chemotherapy (pemetrexed disodium or docetaxel) in patients with advanced non-small cell lung cancer.

- To assess the role of other known tissue-based predictive markers (e.g., EGFR-gene copy number, EGFR-protein expression, pAkt, pMAPK, EGFR mutations, EMT markers, and k-Ras mutation).

OUTLINE: This is a multicenter study. Patients are stratified according to smoking status, performance status, proteomic profile, and participating center. Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive standard chemotherapy with pemetrexed disodium, docetaxel, or another standard drug.

- Arm II: Patients receive standard non-chemotherapy treatment with erlotinib hydrochloride.

Serum is collected after failure of first-line therapy for proteomic analysis by matrix-associated laser desorption/ionization-time of flight. Tissue and blood samples are collected periodically for analysis including EGFR based on IHC and FISH, EGFR and k-Ras mutations, pAkt, pMAPK by IHC, and EMT markers based on IHC and breath condensate protein profile.

After completion of study treatment, patients are followed every 2 months.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both

- Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)

- Advanced NSCLC (stage IIIB or IV)

- Measurable disease

- Underwent previous treatment with 1 non-tyrosine kinase inhibitor as first-line therapy for advanced NSCLC

- No clinical evidence of uncontrolled brain metastases


- Caucasian

- ECOG performance status 0-2

- Absolute granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 2.5 times ULN in patients with known liver metastases)

- ALT or AST ≤ 3 times ULN (≤ 5 times ULN in patients with known liver metastases)

- Creatinine clearance ≥ 50 mL/min

- Not pregnant or nursing

- Able to comply with planned study procedures

- No multiple severe diseases that can compromise safety (cardiac and renal failure, peripheral neuropathy)

- No other malignancy (except for basal cell skin carcinoma) or pre-neoplastic condition requiring chemotherapeutic treatment


- See Disease Characteristics

- At least 3 weeks since prior surgery or radiotherapy
Istituto Scientifico H. San Raffaele
Milan, Italy
Status: Recruiting
Contact: Vanesa Gregor, MD - 39-02-2643-7623
Start Date
February 2008
Istituto Scientifico H. San Raffaele
National Cancer Institute (NCI)
Record processing date processed this data on July 28, 2015 page