Lung Cancer
Conditions
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
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.
Interventions
DRUGbevacizumab
15 mg/m2 given through a vein for every 3 weeks
DRUGcarboplatin
AUC = 6 given through a vein on day 1 of each cycle.
DRUGerlotinib hydrochloride
150 mg taken by mouth daily
DRUGpaclitaxel
200 mg/m2 given through a vein on day 1 of each cycle.
GENETICgene expression analysis
Blood and tissue collection.
GENETICprotein expression analysis
Blood and tissue collection.
GENETICproteomic profiling
Blood and tissue collection.
OTHERlaboratory biomarker analysis
Blood and tissue collection.
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pre-treatment Tumor Proteomic Profile as a Predictor of Response, Stable Disease, or Progressive Disease | End of treatment date |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Proteomic Profiles as Predictors of Response to Carboplatin and Paclitaxel After Failing Treatment With Erlotinib Hydrochloride | End of treatment date | — |
| Analysis of Individual and Pattern(s) of Erlotinib Hydrochloride-induced Genomic and Proteomic Biomarker Changes in Relation to Response or Non-response to Treatment | End of treatment date | End of treatment date |
| Correlation of the Efficacy and Toxicity of Erlotinib Hydrochloride With Expression of EGFR, EGFR Pathway, ErbB Family, and Other Related Biomarkers | End of treatment date | — |
| 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 | End of treatment date | — |
| 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 | End of treatment date | — |
| Progression-free Survival (PFS) for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC | 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. |
| Number of Patients With Worst-grade Toxicities Per Grade | 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 |
| Overall Survival for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC | 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. |
| Response Rate for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC | 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. |
Countries
United States
Participant flow
Recruitment details
The recruitment period for this trial was October 2007 to July 2011. Participants were recruited at Vanderbilt Medical Center, Emory University, M.D. Anderson Cancer Center, University of Florida - Gainesville.
Pre-assignment details
10 participants were consented to participate in this trial, but were determined to be ineligible; 3 participants withdrew from the study prior to beginning treatment; 1 participant progressed before beginning treatment.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression.
bevacizumab: 15 mg/m2 given through a vein for every 3 weeks
carboplatin: AUC = 6 given through a vein on day 1 of each cycle.
erlotinib hydrochloride: 150 mg taken by mouth daily
paclitaxel: 200 mg/m2 given through a vein on day 1 of each cycle.
gene expression analysis: Blood and tissue collection.
protein expression analysis: Blood and tissue collection.
proteomic profiling: Blood and tissue collection.
laboratory biomarker analysis: Blood and tissue collection. | 116 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 20 |
| Overall Study | Change in treatment plan | 4 |
| Overall Study | Death | 18 |
| Overall Study | Declining performance status | 2 |
| Overall Study | Disease progression before | 46 |
| Overall Study | Other complicating ilness | 3 |
| Overall Study | Treated closer to home | 4 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Treatment | — |
|---|---|---|
| Age, Continuous | 70.9 years STANDARD_DEVIATION 11.3 | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | — |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 112 Participants | — |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | — |
| Race (NIH/OMB) Asian | 4 Participants | — |
| Race (NIH/OMB) Black or African American | 7 Participants | — |
| Race (NIH/OMB) More than one race | 1 Participants | — |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | — |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | — |
| Race (NIH/OMB) White | 102 Participants | — |
| Region of Enrollment United States | 116 participants | — |
| Sex: Female, Male Female | 69 Participants | — |
| Sex: Female, Male Male | 47 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 108 / 116 |
| serious Total, serious adverse events | 8 / 116 |
Outcome results
Primary
Pre-treatment Tumor Proteomic Profile as a Predictor of Response, Stable Disease, or Progressive Disease
Time frame: End of treatment date
Population: Lab data was lost by the collaborating institution, Colorado.
Secondary
Analysis of Individual and Pattern(s) of Erlotinib Hydrochloride-induced Genomic and Proteomic Biomarker Changes in Relation to Response or Non-response to Treatment
End of treatment date
Time frame: End of treatment date
Population: Lab data was lost by the collaborating institution, Colorado.
Secondary
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
Population: Lab data was lost by the collaborating institution, Colorado.
Secondary
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
Population: Lab data was lost by the collaborating institution, Colorado.
Secondary
Number of Patients With Worst-grade Toxicities Per Grade
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
Time frame: Through study completion, an average of 1 year
Population: 116 paticipants, one patient was excluded due to death before any treatment. All patients who received erlotinib treatment and experienced an Adverse events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment | Number of Patients With Worst-grade Toxicities Per Grade | worst-grade 1 | 18 participants |
| Treatment | Number of Patients With Worst-grade Toxicities Per Grade | worst-grade 2 | 51 participants |
| Treatment | Number of Patients With Worst-grade Toxicities Per Grade | worst-grade 3 | 15 participants |
| Treatment | Number of Patients With Worst-grade Toxicities Per Grade | worst-grade 4 | 1 participants |
Secondary
Overall Survival for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
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.
Time frame: Through study completion, an average of 1 year
Population: Total 116 participants. One patient was excluded due to death before any treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment | Overall Survival for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC | 12.53 months |
| Erlotinib Followed by PC+B | Overall Survival for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC | 17.23 months |
| Erlotinib | Overall Survival for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC | 6.08 months |
Secondary
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
Population: Lab data was lost by the collaborating institution, Colorado.
Secondary
Progression-free Survival (PFS) for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
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.
Time frame: Through study completion, an average of 1 year
Population: Total 116 participants. One patient was excluded due to death before erlotinib treatment. Total 115 patients were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment | Progression-free Survival (PFS) for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC | 3.16 months |
Secondary
Response Rate for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
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.
Time frame: Through study completion, an average of 1 year
Population: Total 116 participants, 11 not assessed and 4 not evaluable. 101 assessed for response.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment | Response Rate for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC | 18.8 percentage of patients assessed |
Secondary
Tumor Proteomic Profiles as Predictors of Response to Carboplatin and Paclitaxel After Failing Treatment With Erlotinib Hydrochloride
Time frame: End of treatment date
Population: Lab data was lost by the collaborating institution, Colorado.