Lung CancerPhase 2NCT00550537
Proteomic Profiling in Predicting Response in Patients Receiving Erlotinib for Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer
A Phase 2 study testing bevacizumab, carboplatin and erlotinib hydrochloride in people with Lung Cancer, run by Vanderbilt-Ingram Cancer Center at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Lung Cancer
- What is being tested?
- bevacizumab, carboplatin and erlotinib hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 7 sitesUnited States
- Study dates
- Oct 2007to Dec 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109-0942
Emory University
Atlanta, Georgia, 30308
University of Florida Shands Cancer Center
Gainesville, Florida, 32610-0232
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, 37064
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, 37064
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
About this study
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
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.
Read the 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.
- Conditions
- Lung Cancer
- Being tested
- bevacizumab, carboplatin, erlotinib hydrochloride, paclitaxel, gene expression analysis
- 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
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Adenocarcinoma, Bronchiolo-Alveolar, Adenocarcinoma of Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabDrug
15 mg/m2 given through a vein for every 3 weeks
carboplatinDrug
AUC = 6 given through a vein on day 1 of each cycle.
erlotinib hydrochlorideDrug
150 mg taken by mouth daily
paclitaxelDrug
200 mg/m2 given through a vein on day 1 of each cycle.
gene expression analysisGenetic
Blood and tissue collection.
protein expression analysisGenetic
Blood and tissue collection.
proteomic profilingGenetic
Blood and tissue collection.
laboratory biomarker analysisOther
Blood and tissue collection.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression. Receives: Drug: bevacizumab; Drug: carboplatin; Drug: erlotinib hydrochloride; Drug: paclitaxel; Genetic: gene expression analysis; Genetic: protein expression analysis; Genetic: proteomic profiling; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pre-treatment Tumor Proteomic Profile as a Predictor of Response, Stable Disease, or Progressive Disease
Measured: End of treatment date
Secondary outcomes (9)
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
Measured: End of treatment date
Tumor Proteomic Profiles as Predictors of Response to Carboplatin and Paclitaxel After Failing Treatment With Erlotinib Hydrochloride
Measured: 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
Measured: 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
Measured: 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
Measured: End of treatment date
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.
Measured: Through study completion, an average of 1 year
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.
Measured: Through study completion, an average of 1 year
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
Measured: Through study completion, an average of 1 year
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.
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2007 (estimated)
- Study startOct 2007
- Primary completionSep 2011
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Leora Horn, MD, Vanderbilt-Ingram Cancer Center
- Investigators
- David Carbone, M.D., Ph.D., Study chair, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00550537
- Sponsor's protocol ID
- VICC-THO-0640
- Other IDs
- P30CA068485, VU-VICC-THO-0640, VU-VICC-070494
- Status last verified
- May 2017
- First submitted
- 26 Oct 2007
- Last updated
- 8 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00550537
- Acronym / sponsor ID
- VICC-THO-0640
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Oct 2007
- Primary completion
- Sep 2011 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 30 Oct 2007 (estimated)
- Results
- Posted 25 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: bevacizumab, Drug: carboplatin, Drug: erlotinib hydrochloride, Drug: paclitaxel, Genetic: gene expression analysis, Genetic: protein expression analysis, Genetic: proteomic profiling, Other: laboratory biomarker analysisErlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bevacizumab15 mg/m2 given through a vein for every 3 weeks | Drug | Treatment |
| carboplatinAUC = 6 given through a vein on day 1 of each cycle. | Drug | Treatment |
| erlotinib hydrochloride150 mg taken by mouth daily | Drug | Treatment |
| paclitaxel200 mg/m2 given through a vein on day 1 of each cycle. | Drug | Treatment |
| gene expression analysisBlood and tissue collection. | Genetic | Treatment |
| protein expression analysisBlood and tissue collection. | Genetic | Treatment |
| proteomic profilingBlood and tissue collection. | Genetic | Treatment |
| laboratory biomarker analysisBlood and tissue collection. | Other | Treatment |
Primary outcome
Pre-treatment Tumor Proteomic Profile as a Predictor of Response, Stable Disease, or Progressive Disease
Time frame: End of treatment date
9 secondary outcomes
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
Tumor Proteomic Profiles as Predictors of Response to Carboplatin and Paclitaxel After Failing Treatment With Erlotinib Hydrochloride
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: End of treatment date
Response Rate for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
Time frame: Through study completion, an average of 1 year
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
Number of Patients With Worst-grade Toxicities Per Grade
Time frame: Through study completion, an average of 1 year
Overall Survival for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
Time frame: Through study completion, an average of 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Carbone, M.D., Ph.D. study chair
Vanderbilt-Ingram Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bevacizumab, carboplatin and erlotinib hydrochloride in people with Lung Cancer, run by Vanderbilt-Ingram Cancer Center at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pre-treatment Tumor Proteomic Profile as a Predictor of Response, Stable Disease, or Progressive Disease (time frame: End of treatment date). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2017.