Clinical trial NCT00550537: Proteomic Profiling in Predicting Response in Patients Receiving Erlotinib for Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer
Official title: A Feasibility Study Investigating Translational Science in Chemotherapy-Naive Patients With Stage IIIb or IV Non-Small Cell Lung Cancer (NSCLC) Treated With the EGFR-TKI, Erlotinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent non-small cell lung cancer
squamous cell lung cancer
adenosquamous cell lung cancer
bronchoalveolar cell lung cancer
large cell lung cancer
adenocarcinoma of the lung
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-10-30
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Studying samples of tumor tissue, blood, and urine in the laboratory from patients receiving erlotinib may help doctors predict how patients will respond to treatment.

PURPOSE: The phase II trial is studying proteomic profiling to see how well it predicts response in patients receiving erlotinib for stage IIIB, stage IV, or recurrent non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* To define a pre-treatment tumor proteomic profile that predicts response, stable disease, or progressive disease in patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer treated with erlotinib hydrochloride.

Secondary

* To test and refine a pre-treatment serum proteomic expression pattern that predicts response to erlotinib hydrochloride and/or carboplatin and paclitaxel after failing treatment with erlotinib hydrochloride.
* To test and refine tumor proteomic profiles that predict response to carboplatin and paclitaxel after failing treatment with erlotinib hydrochloride.
* To analyze individual and pattern(s) of erlotinib hydrochloride-induced genomic and proteomic biomarker changes in relation to response or non-response to treatment.
* To correlate the efficacy and toxicity of erlotinib hydrochloride with expression of EGFR, EGFR pathway, ErbB family, and other related biomarkers.
* To determine a set of biomarkers to be evaluated in tumor tissue or surrogate tissues prior to treatment with erlotinib hydrochloride to enable patient selection for therapy.
* To estimate response rate and progression-free and overall survival of patients treated with erlotinib hydrochloride as initial therapy.
* To characterize the safety profile of erlotinib hydrochloride in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride once daily until disease progression.

At the time of disease progression, patients receive standard chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Patients with non-squamous cell non-small cell lung cancer also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses.

Tumor tissue, plasma, serum, and urine samples are collected at baseline for proteomics analysis.

After the completion of study treatment, patients are followed every 8 weeks.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed non-small cell lung cancer (NSCLC), meeting 1 of the following criteria:

  * Stage IIIB (with pleural effusion) or stage IV disease
  * Recurrent disease after prior surgery
* Measurable or evaluable disease is desirable but not required
* No untreated symptomatic brain metastases

  * Patients who are neurologically unstable despite radiotherapy for the brain metastases are not eligible
  * No requirement for steroids to control neurological symptoms

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* ANC ≥ 1,500/mm³
* Hemoglobin ≥ 9 g/dL
* Platelet count ≥ 100,000/mm³
* Creatinine ≤ 2.0 mg/dL
* Total bilirubin ≤ 1.5 mg/dL
* Normal hemostasis by history
* PT/PTT within 0.5 seconds of normal range
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Willing to undergo biopsy procedures
* No known severe hypersensitivity to erlotinib hydrochloride or any of the excipients of this product
* No other concurrent malignancies or malignancies diagnosed within the past 5 years, except basal cell carcinoma or cervical cancer in situ
* No significant cardiac disease, including any of the following:

  * NYHA class III or IV heart disease
  * Uncontrolled dysrhythmia
  * Myocardial infarction within the past 6 months
* No evidence of clinically active interstitial lung disease

  * Chronic stable radiographic changes that are asymptomatic allowed
* No evidence of any other severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
* No evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial
* No uncontrolled hypertension

  * Blood pressure must be ≤ 150/90 mmHg on a stable antihypertensive regimen

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 6 months since prior adjuvant chemotherapy
* No unresolved chronic toxicity \> CTC grade 2 from prior anticancer therapy (except alopecia)
* More than 30 days since prior non-approved or investigational drugs
* No prior chemotherapy for advanced NSCLC
* No concurrent phenytoin, carbamazepine, rifampin, barbiturates, or St. John's wort
* No concurrent administration of other drugs known to inhibit EGFR
* No other concurrent anti-neoplastic or anti-tumor agents, including chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy
* No other concurrent investigational agents
* Concurrent cardioprotective doses of aspirin, as recommended by the physician, for cardiovascular disease allowed

Primary outcomes:
measure: Pre-treatment Tumor Proteomic Profile as a Predictor of Response, Stable Disease, or Progressive Disease
timeFrame: End of treatment date
Secondary outcomes:
measure: Pre-treatment Serum Proteomic Expression Pattern as a Predictor of Response to Erlotinib Hydrochloride and/or Carboplatin and Paclitaxel After Failing Treatment With Erlotinib Hydrochloride
timeFrame: End of treatment date
measure: Tumor Proteomic Profiles as Predictors of Response to Carboplatin and Paclitaxel After Failing Treatment With Erlotinib Hydrochloride
timeFrame: End of treatment date
measure: Analysis of Individual and Pattern(s) of Erlotinib Hydrochloride-induced Genomic and Proteomic Biomarker Changes in Relation to Response or Non-response to Treatment
timeFrame: End of treatment date
measure: Correlation of the Efficacy and Toxicity of Erlotinib Hydrochloride With Expression of EGFR, EGFR Pathway, ErbB Family, and Other Related Biomarkers
timeFrame: End of treatment date
measure: Determination of a Set of Biomarkers to be Evaluated in Tumor Tissue or Surrogate Tissues Prior to Treatment With Erlotinib Hydrochloride to Enable Patient Selection for Therapy
timeFrame: End of treatment date
measure: Response Rate for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
timeFrame: Through study completion, an average of 1 year
measure: Progression-free Survival (PFS) for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
timeFrame: Through study completion, an average of 1 year
measure: Number of Patients With Worst-grade Toxicities Per Grade
timeFrame: Through study completion, an average of 1 year
measure: Overall Survival for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center - Cool Springs
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Franklin
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: David Carbone, M.D., Ph.D.
role: STUDY_CHAIR
References: