Clinical trial NCT00989690: 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
Official title: Randomized Proteomic Stratified Phase III Study of Second-Line Erlotinib Versus Chemotherapy in Patients With Inoperable Non Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Lung Cancer
Keywords: recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2009-10-05
Enrollment: 275
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Overall survival
Secondary outcomes:
measure: Progression-free survival
measure: Overall response rate according to RECIST criteria
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Istituto Scientifico H. San Raffaele
Study officials:
affiliation: Istituto Scientifico H. San Raffaele
name: Vanesa Gregor, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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, Vigano 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.