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

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
Lung Cancer	Drug: docetaxel; Drug: erlotinib hydrochloride; Drug: pemetrexed disodium; Genetic: fluorescence in situ hybridization; Genetic: mutation analysis; Genetic: proteomic profiling; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Other: matrix-assisted laser desorption/ionization time of flight mass spectrometry; Procedure: breath test	Phase 3

Detailed 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	275 participants
Allocation:	Randomized
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Randomized Proteomic Stratified Phase III Study of Second-Line Erlotinib Versus Chemotherapy in Patients With Inoperable Non Small Cell Lung Cancer
Study Start Date :	February 2008

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

1. Overall survival

Secondary Outcome Measures :

1. Progression-free survival
2. Overall response rate according to RECIST criteria

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

Italy
Istituto Scientifico H. San Raffaele	Recruiting
Milan, Italy, 20132
Contact: Vanesa Gregor, MD 39-02-2643-7623

Sponsors and Collaborators

Istituto Scientifico H. San Raffaele

Investigators

Principal Investigator:	Vanesa Gregor, MD	Istituto Scientifico H. San Raffaele

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gregorc V, Novello S, Lazzari C, Barni S, Aieta M, Mencoboni M, Grossi F, De Pas T, de Marinis F, Bearz A, Floriani I, Torri V, Bulotta A, Cattaneo A, Grigorieva J, Tsypin M, Roder J, Doglioni C, Levra MG, Petrelli F, Foti S, Viganò M, Bachi A, Roder H. Predictive value of a proteomic signature in patients with non-small-cell lung cancer treated with second-line erlotinib or chemotherapy (PROSE): a biomarker-stratified, randomised phase 3 trial. Lancet Oncol. 2014 Jun;15(7):713-21. doi: 10.1016/S1470-2045(14)70162-7. Epub 2014 May 13.

ClinicalTrials.gov Identifier:	NCT00989690 History of Changes
Other Study ID Numbers:	SRSI-HSRL-02-2007; CDR0000652115 ( Registry Identifier: PDQ (Physician Data Query) ); 2007-006299-13; EU-20975
First Posted:	October 5, 2009
Last Update Posted:	August 12, 2013
Last Verified:	October 2009

Keywords provided by National Cancer Institute (NCI):

recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic	Bronchial Neoplasms; Erlotinib Hydrochloride; Pemetrexed; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors