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

Primary Purpose

Lung Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

bevacizumab

carboplatin

erlotinib hydrochloride

paclitaxel

gene expression analysis

protein expression analysis

proteomic profiling

laboratory biomarker analysis

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Florida Shands Cancer Center
Emory University
University of Michigan Comprehensive Cancer Center
Vanderbilt-Ingram Cancer Center - Cool Springs
Vanderbilt-Ingram Cancer Center at Franklin
Vanderbilt-Ingram Cancer Center
M. D. Anderson Cancer Center at University of Texas

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression.

Outcomes

Primary Outcome Measures

Pre-treatment Tumor Proteomic Profile as a Predictor of Response, Stable Disease, or Progressive Disease

Secondary Outcome Measures

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

Tumor Proteomic Profiles as Predictors of Response to Carboplatin and Paclitaxel After Failing Treatment With Erlotinib Hydrochloride

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

Correlation of the Efficacy and Toxicity of Erlotinib Hydrochloride With Expression of EGFR, EGFR Pathway, ErbB Family, and Other Related Biomarkers

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

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.

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.

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

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.

Full Information

NCT ID

NCT00550537

First Posted

October 26, 2007

Last Updated

May 12, 2017

Sponsor

Vanderbilt-Ingram Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00550537

Brief Title

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

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Completed

Study Start Date

October 2007 (undefined)

Primary Completion Date

September 2011 (Actual)

Study Completion Date

December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vanderbilt-Ingram Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

116 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression.

Intervention Type

Drug

Intervention Name(s)

bevacizumab

Intervention Description

15 mg/m2 given through a vein for every 3 weeks

Intervention Type

Drug

Intervention Name(s)

carboplatin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

erlotinib hydrochloride

Intervention Description

150 mg taken by mouth daily

Intervention Type

Drug

Intervention Name(s)

paclitaxel

Intervention Description

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

Intervention Type

Genetic

Intervention Name(s)

gene expression analysis

Intervention Description

Blood and tissue collection.

Intervention Type

Genetic

Intervention Name(s)

protein expression analysis

Intervention Description

Blood and tissue collection.

Intervention Type

Genetic

Intervention Name(s)

proteomic profiling

Intervention Description

Blood and tissue collection.

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

Blood and tissue collection.

Primary Outcome Measure Information:

Title

Pre-treatment Tumor Proteomic Profile as a Predictor of Response, Stable Disease, or Progressive Disease

Time Frame

End of treatment date

Secondary Outcome Measure Information:

Title

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

Title

Tumor Proteomic Profiles as Predictors of Response to Carboplatin and Paclitaxel After Failing Treatment With Erlotinib Hydrochloride

Time Frame

End of treatment date

Title

Analysis of Individual and Pattern(s) of Erlotinib Hydrochloride-induced Genomic and Proteomic Biomarker Changes in Relation to Response or Non-response to Treatment

Description

End of treatment date

Time Frame

End of treatment date

Title

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

Title

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

Title

Response Rate for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC

Description

Time Frame

Through study completion, an average of 1 year

Title

Progression-free Survival (PFS) for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC

Description

Time Frame

Through study completion, an average of 1 year

Title

Number of Patients With Worst-grade Toxicities Per Grade

Description

Time Frame

Through study completion, an average of 1 year

Title

Overall Survival for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC

Description

Time Frame

Through study completion, an average of 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Carbone, M.D., Ph.D.

Organizational Affiliation

Vanderbilt-Ingram Cancer Center

Official's Role

Study Chair

Facility Information:

Facility Name

University of Florida Shands Cancer Center

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32610-0232

Country

United States

Facility Name

Emory University

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30308

Country

United States

Facility Name

University of Michigan Comprehensive Cancer Center

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109-0942

Country

United States

Facility Name

Vanderbilt-Ingram Cancer Center - Cool Springs

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37064

Country

United States

Facility Name

Vanderbilt-Ingram Cancer Center at Franklin

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37064

Country

United States

Facility Name

Vanderbilt-Ingram Cancer Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232-6838

Country

United States

Facility Name

M. D. Anderson Cancer Center at University of Texas

City

Houston

State/Province

Texas

ZIP/Postal Code

77030-4009

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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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