Erlotinib Hydrochloride With or Without Celecoxib in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer

Phase 2

Completed

• Conditions: Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer
• Interventions: Drug: erlotinib hydrochloride; Drug: celecoxib; Other: placebo; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: fluorescence in situ hybridization; Genetic: mutation analysis; Genetic: protein expression analysis; Genetic: gene expression analysis

• Registration Number: NCT00499655
• Lead Sponsor: City of Hope Medical Center

Brief Summary

RATIONALE: Erlotinib hydrochloride and celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Celecoxib may also stop the growth of lung cancer by blocking blood flow to the tumor. Giving erlotinib hydrochloride together with celecoxib may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving erlotinib hydrochloride together with celecoxib works compared with erlotinib hydrochloride alone in treating patients with stage IIIB-IV non-small cell lung cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. Comparison of progression-free survival (PFS) in patients receiving erlotinib + celecoxib vs. erlotinib + placebo for advanced NSCLC.

SECONDARY OBJECTIVES:

I. Objective tumor response rate as defined by RECIST Criteria for subjects receiving erlotinib/celecoxib treatment arms.

II. Categorize the change in e-cadherin expression from baseline to week 8 in a subset of subjects.

III. Evaluation of overall survival (OS). IV. Measurement of COX-2, EGFR by immunohistochemistry and EGFR amplification by FISH, and EGFR mutation status to correlate with clinical response.

V. Measurement of change in urinary PGE-M and correlation with response.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral erlotinib hydrochloride once daily and oral placebo twice daily on days 1-28.

ARM II: Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily on days 1-28.

In both arms, treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Study Timeline

• Study First Submitted: 2007-07-10
• Study First Submitted QC: 2007-07-10
• Study First Posted: 2007-07-11
• Study Start: 2007-11
• Primary Completion: 2016-12
• Study Completion: 2016-12
• Results First Submitted: 2017-01-06
• Results First Submitted QC: 2017-01-06
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-28
• Results First Posted: 2017-03-01
• Last Update Posted: 2017-03-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 107

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II	laboratory biomarker analysis	Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily on days 1-28.
Arm I	erlotinib hydrochloride	Patients receive oral erlotinib hydrochloride once daily and oral placebo twice daily on days 1-28.
Arm I	protein expression analysis	Patients receive oral erlotinib hydrochloride once daily and oral placebo twice daily on days 1-28.
Arm I	gene expression analysis	Patients receive oral erlotinib hydrochloride once daily and oral placebo twice daily on days 1-28.
Arm II	celecoxib	Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily on days 1-28.
Arm I	placebo	Patients receive oral erlotinib hydrochloride once daily and oral placebo twice daily on days 1-28.
Arm I	immunohistochemistry staining method	Patients receive oral erlotinib hydrochloride once daily and oral placebo twice daily on days 1-28.
Arm I	fluorescence in situ hybridization	Patients receive oral erlotinib hydrochloride once daily and oral placebo twice daily on days 1-28.
Arm II	mutation analysis	Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily on days 1-28.
Arm I	laboratory biomarker analysis	Patients receive oral erlotinib hydrochloride once daily and oral placebo twice daily on days 1-28.
Arm II	fluorescence in situ hybridization	Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily on days 1-28.
Arm I	mutation analysis	Patients receive oral erlotinib hydrochloride once daily and oral placebo twice daily on days 1-28.
Arm II	immunohistochemistry staining method	Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily on days 1-28.
Arm II	erlotinib hydrochloride	Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily on days 1-28.
Arm II	protein expression analysis	Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily on days 1-28.
Arm II	gene expression analysis	Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily on days 1-28.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	Until disease progression, up to 5 years.	Estimated using the product-limit method of Kaplan and Meier.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Overall Response	16 weeks post start of treatment	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Progression-free Survival - Elevated PGEM	Until disease progression, up to 5 years.	Estimated using the product-limit method of Kaplan and Meier.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Progression-free Survival - Low PGEM	Until disease progression, up to 5 years.	Estimated using the product-limit method of Kaplan and Meier.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Progression-free Survival - EGRF	Until disease progression, up to 5 years.	Estimated using the product-limit method of Kaplan and Meier.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

Trial Locations

Locations (2)

South Pasadena Cancer Center; 🇺🇸 South Pasadena, California, United States

City of Hope Medical Center; 🇺🇸 Duarte, California, United States