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 Clinical Trial

Official title:

Randomized Proteomic Stratified Phase III Study of Second-Line Erlotinib Versus Chemotherapy in Patients With Inoperable Non Small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00989690
• Other study ID #: SRSI-HSRL-02-2007
• Secondary ID: CDR0000652115200
• Status: Recruiting
• Phase: Phase 3
• First received: October 2, 2009
• Last updated: August 9, 2013
• Start date: February 2008

Study information

• Verified date: October 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

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.

Description:

OBJECTIVES:

• 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 275
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 3 weeks since prior surgery or radiotherapy

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• docetaxel

• erlotinib hydrochloride

• pemetrexed disodium

Genetic:
• fluorescence in situ hybridization

• mutation analysis

• proteomic profiling

Other:
• immunohistochemistry staining method

• laboratory biomarker analysis

• matrix-assisted laser desorption/ionization time of flight mass spectrometry

Procedure:
• breath test

Locations

Country	Name	City	State
Italy	Istituto Scientifico H. San Raffaele	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Scientifico H. San Raffaele

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival			No
Secondary	Progression-free survival			No
Secondary	Overall response rate according to RECIST criteria			No