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Trial record 18 of 24 for:    "Adenosquamous Lung Carcinoma" | "Antineoplastic Agents, Phytogenic"

Proteomic Profiling in Predicting Response in Patients Receiving Erlotinib for Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT00550537
Recruitment Status : Completed
First Posted : October 30, 2007
Results First Posted : April 25, 2017
Last Update Posted : June 8, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Leora Horn, MD, Vanderbilt-Ingram Cancer Center

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.


Condition or disease Intervention/treatment Phase
Lung Cancer Drug: bevacizumab Drug: carboplatin Drug: erlotinib hydrochloride Drug: paclitaxel Genetic: gene expression analysis Genetic: protein expression analysis Genetic: proteomic profiling Other: laboratory biomarker analysis Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 116 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : October 2007
Actual Primary Completion Date : September 2011
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Treatment
Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression.
Drug: bevacizumab
15 mg/m2 given through a vein for every 3 weeks

Drug: carboplatin
AUC = 6 given through a vein on day 1 of each cycle.

Drug: erlotinib hydrochloride
150 mg taken by mouth daily

Drug: paclitaxel
200 mg/m2 given through a vein on day 1 of each cycle.

Genetic: gene expression analysis
Blood and tissue collection.

Genetic: protein expression analysis
Blood and tissue collection.

Genetic: proteomic profiling
Blood and tissue collection.

Other: laboratory biomarker analysis
Blood and tissue collection.




Primary Outcome Measures :
  1. Pre-treatment Tumor Proteomic Profile as a Predictor of Response, Stable Disease, or Progressive Disease [ Time Frame: End of treatment date ]

Secondary Outcome Measures :
  1. 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 [ Time Frame: End of treatment date ]
  2. Tumor Proteomic Profiles as Predictors of Response to Carboplatin and Paclitaxel After Failing Treatment With Erlotinib Hydrochloride [ Time Frame: End of treatment date ]
  3. Analysis of Individual and Pattern(s) of Erlotinib Hydrochloride-induced Genomic and Proteomic Biomarker Changes in Relation to Response or Non-response to Treatment [ Time Frame: End of treatment date ]
    End of treatment date

  4. Correlation of the Efficacy and Toxicity of Erlotinib Hydrochloride With Expression of EGFR, EGFR Pathway, ErbB Family, and Other Related Biomarkers [ Time Frame: End of treatment date ]
  5. 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 [ Time Frame: End of treatment date ]
  6. Response Rate for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC [ Time Frame: Through study completion, an average of 1 year ]
    Number of patients in each response category, per RECIST v1.1, summarized as follows for target lesion criteria (see RECIST v1.1 for additional details): complete response (CR),disappearance of target lesions; partial response (PR), >=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), >=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD. The response rate is calculated as the percentage of PR+CR among patients assessed for response.

  7. Progression-free Survival (PFS) for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC [ Time Frame: Through study completion, an average of 1 year ]
    PFS is defined as the time from on erlotinib treatment date to progression or death (whichever comes first) before cross-over to PC or PC+B. For those did not progressed nor died, they were censored at the last follow up (either the off erlotinib treatment date or lost follow up date). The median survival time and 95% confidence interval were estimated using Kaplan-meier method.

  8. Number of Patients With Worst-grade Toxicities Per Grade [ Time Frame: Through study completion, an average of 1 year ]

    The intensity of the AE will be graded according to the Common Toxicity Criteria (CTC) of the (US) National Cancer Institute (NCI) - Cancer Therapy Evaluation Program (CTEP) [version 3.0 of December 2003] (Appendix B).

    Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE


  9. Overall Survival for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC [ Time Frame: Through study completion, an average of 1 year ]
    The overall survival time is defined as the time from on treatment to death. Patients were censored of they were alive at the last follow up date. The median survival time and its confidence interval were estimated using Kaplan-meier method.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00550537


Locations
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United States, Florida
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30308
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0942
United States, Tennessee
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
National Cancer Institute (NCI)
Investigators
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Study Chair: David Carbone, M.D., Ph.D. Vanderbilt-Ingram Cancer Center

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Responsible Party: Leora Horn, MD, Assistant Professor of Medicine, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00550537     History of Changes
Other Study ID Numbers: VICC-THO-0640
P30CA068485 ( U.S. NIH Grant/Contract )
VU-VICC-THO-0640
VU-VICC-070494
First Posted: October 30, 2007    Key Record Dates
Results First Posted: April 25, 2017
Last Update Posted: June 8, 2017
Last Verified: May 2017

Keywords provided by Leora Horn, MD, Vanderbilt-Ingram Cancer Center:
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

Additional relevant MeSH terms:
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Antineoplastic Agents, Phytogenic
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
Paclitaxel
Bevacizumab
Carboplatin
Erlotinib Hydrochloride
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors