CompletedNCT00499655Updated Mar 29, 2017Results posted

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

A Phase 2 interventional study of erlotinib hydrochloride and celecoxib in Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer and Stage IV Non-small Cell Lung Cancer, sponsored by City of Hope Medical Center. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-03-29.

Sponsored by City of Hope Medical Center · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 107
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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.

Read the 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.

Conditions studied

Recurrent Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer

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In context

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,558 are open to participants now.

This study's enrollment of 107 is above the median of 60 across 5,296 interventional studies indexed under Lung Neoplasms.

Browse Lung Neoplasms studies →

Lead sponsor

City of Hope Medical Center is the lead sponsor of 670 studies on the registry; 181 are open to participants now.

Of its 30 completed or terminated interventional studies of FDA-regulated products, 12 (40%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Pathologically proven NSCLC, stage IIIB (defined as: with pleural effusion or recurrence after mediastinal radiation and chemotherapy) or IV
Available tumor tissue for mutation screening
Measurable stage IIIb or IV disease by RECIST guidelines
ECOG performance status of 0 or 1
Progressive disease despite >= 1 prior chemotherapy regimens as standard of care or subject's refusal or inability to receive standard chemotherapy
Normal renal function (defined as serum creatinine =\< 2mg/dl)
Normal liver function (defined as serum total bilirubin =\< 1.5, and serum transaminases =\< 2.5X the upper limits of normal [ULN]); if liver metastases are present, serum transaminases > 5X the ULN
No evidence of coagulopathy (defined as PT and/or PTT =\< 1.5X ULN or platelets >= 100,000)
No evidence of leukopenia (defined as absolute neutrophil count >= 1,500 mm\^3)
Negative pregnancy test prior to initiation of treatment and adequate contraception throughout treatment

Exclusion criteria

Exclusion

Cytotoxic chemotherapy agents within 4 weeks of initiating treatment; all toxicities must be recovered to baseline or NCI CTCAE v3.0 Grade 1 from all acute effects of prior cancer treatment, except alopecia or any clinically insignificant effect, prior to study initiation
Evidence of NYHA class III or greater cardiac disease, history of myocardial infarction, cerebral vascular accident, symptomatic ventricular arrhythmia, or symptomatic conduction abnormality
Non-cytoxic therapy within 2 weeks of initiating treatment ; all toxicities must be recovered to baseline or NCI CTCAE v3.0 Grade 1 from all acute effects of prior cancer treatment, except alopecia or any clinically insignificant effect, prior to study initiation
Prior radiotherapy to target lesions is not permitted unless completed more than 4 weeks prior to treatment within the study and that there has been documented progression at these sites (Radiotherapy to non-target lesions is permitted within 2 weeks of study entry provided all acute effects of the radiotherapy have resolved at least grade 1)
Comorbid disease or a medical condition that would impair the ability of the subject to receive or comply with the study protocol
Prior malignancy within the last 3 years with the exception of non-melanoma skin cancer or cervical cancer in situ
Hypersensitivity of erlotinib or celecoxib or to any of the excipients of these products
Hypersensitivity to sulfonamides, aspirin or other NSAIDS
Prior history of EGFR inhibitor for the treatment of cancer
Previous history of gastrointestinal ulceration, bleeding or perforation
Concurrent use of COX-2 inhibitors or other NSAIDS (For subjects on NSAIDS prior to study initiation, cessation of the drug for 72 hours prior to study entry is required)
Chronic or concurrent use of steroids (topical steroids are acceptable if medically indicated)
Subjects who require treatment with fluconazole or lithium
Any evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded)
Renal insufficiency (defined as serum creatinine > 2 mg/dl)
Liver insufficiency (defined as serum total bilirubin > 1.5, or serum transaminases > 2.5C the upper limits of normal [ULN]); if liver metastases are present, serum transaminases > 5X the ULN
Coagulopathy (defined as PT and/or PTT > 1.5X ULN or platelets \< 100,000)
Leukopenia (defined as absolute neutrophil count \< 1,500/mm\^3)
Pregnancy or inadequate contraception
Lactating females
Active CNS metastasis (stable, treated CNS metastasis acceptable)

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 107 participants (actual)

Study arms

Active comparator
Arm I
Patients receive oral erlotinib hydrochloride once daily and oral placebo twice daily on days 1-28.
Drug: erlotinib hydrochloride · 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
Experimental
Arm II
Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily on days 1-28.
Drug: erlotinib hydrochloride · Drug: celecoxib · Other: laboratory biomarker analysis · Other: immunohistochemistry staining method · Genetic: fluorescence in situ hybridization · Genetic: mutation analysis · Genetic: protein expression analysis · Genetic: gene expression analysis

Interventions

Drugerlotinib hydrochloride
Given orally
Also known as: CP-358,774, erlotinib, OSI-774, Tarceva
Drugcelecoxib
Given orally
Also known as: Celebrex, SC-58635, YM 177
Otherplacebo
Given orally
Also known as: PLCB
Otherlaboratory biomarker analysis
Correlative studies
Otherimmunohistochemistry staining method
Correlative studies
Also known as: immunohistochemistry
Geneticfluorescence in situ hybridization
Correlative studies
Also known as: fluorescence in situ hybridization (FISH)
Geneticmutation analysis
Correlative studies
Geneticprotein expression analysis
Correlative studies
Geneticgene expression analysis
Correlative studies

What researchers measure

Primary outcomes

Progression-free Survival
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.
Time frame: Until disease progression, up to 5 years.

Secondary outcomes

Number of Participants With Overall Response
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
Time frame: 16 weeks post start of treatment
Progression-free Survival - Elevated PGEM
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.
Time frame: Until disease progression, up to 5 years.
Progression-free Survival - EGRF
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.
Time frame: Until disease progression, up to 5 years.
Progression-free Survival - Low PGEM
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.
Time frame: Until disease progression, up to 5 years.

Results

Posted Mar 1, 2017

Participant flow

Participant flow — Overall Study
Milestone	Erlotinib\Placebo	Erlotinib\Celecoxib
Started	53	54
Completed	53	54
Not completed	0	0

Outcome measures

PrimaryProgression-free Survival

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.

Time frame:: Until disease progression, up to 5 years.
Reported as:: Median · Months

Progression-free Survival
Months	Erlotinib\Placebo	Erlotinib\Celecoxib
Progression-free Survival	3.5 (1.8 to 5.5)	5.4 (2 to 7.6)

SecondaryNumber of Participants With Overall Response

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

Time frame:: 16 weeks post start of treatment
Reported as:: Count of participants · Participants

Number of Participants With Overall Response
Participants	Erlotinib\Placebo	Erlotinib\Celecoxib
Number of Participants With Overall Response	17	12

SecondaryProgression-free Survival - Elevated PGEM

Time frame:: Until disease progression, up to 5 years.
Reported as:: Median · Months

Progression-free Survival - Elevated PGEM
Months	Erlotinib\Placebo	Erlotinib\Celecoxib
Progression-free Survival - Elevated PGEM	2.2 (1.8 to 5.5)	5.4 (1.8 to 12.9)

SecondaryProgression-free Survival - EGRF

Time frame:: Until disease progression, up to 5 years.
Reported as:: Median · Months

Progression-free Survival - EGRF
Months	Erlotinib\Placebo	Erlotinib\Celecoxib
Progression-free Survival - EGRF	1.8 (1.7 to 3.5)	3.2 (1.7 to 6.7)

SecondaryProgression-free Survival - Low PGEM

Time frame:: Until disease progression, up to 5 years.
Reported as:: Median · Months

Progression-free Survival - Low PGEM
Months	Erlotinib\Placebo	Erlotinib\Celecoxib
Progression-free Survival - Low PGEM	5.4 (1.7 to 7.2)	6.8 (1.7 to 9.0)

Adverse events

Collected over Adverse events occurred over a period of 6 years.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Erlotinib\Placebo	—	1/53 (1.9%)	53/53 (100%)
Erlotinib\Celecoxib	—	2/54 (3.7%)	54/54 (100%)

Most frequent serious events

Most frequent serious events
Event	Erlotinib\Placebo	Erlotinib\Celecoxib
cerebrovascular ischemiaVascular disorders	0/53	2/54
cardiac ischemiaVascular disorders	1/53	0/54

Most frequent other events

Showing 10 of 17

Most frequent other events
Event	Erlotinib\Placebo	Erlotinib\Celecoxib
RashSkin and subcutaneous tissue disorders	42/53	43/54
DiarrheaGastrointestinal disorders	40/53	38/54
Dry skinSkin and subcutaneous tissue disorders	40/53	36/54
FatigueGeneral disorders	31/53	28/54
Elevated ASTInvestigations	27/53	25/54
AnorexiaPsychiatric disorders	26/53	17/54
AnemiaBlood and lymphatic system disorders	8/53	18/54
NauseaGeneral disorders	17/53	14/54
Elevated creatinineInvestigations	8/53	17/54
HypoalbuminemiaInvestigations	14/53	16/54

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Erlotinib\Placebo	Erlotinib\Celecoxib	Total
Median	65 (30 to 80)	63.5 (41 to 80)	64 (30 to 80)

Sex: Female, Male
Sex: Female, Male(Participants)	Erlotinib\Placebo	Erlotinib\Celecoxib	Total
Female	29	28	57
Male	24	26	50

Region of Enrollment
Region of Enrollment(Participants)	Erlotinib\Placebo	Erlotinib\Celecoxib	Total
United States	53	54	107

Study locations

2 sites

City of Hope Medical Center
Duarte, California 91010, United States
South Pasadena Cancer Center
South Pasadena, California 91030, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 29, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00499655
Lead sponsor: City of Hope Medical Center
Collaborators: OSI Pharmaceuticals
Responsible party: Sponsor
First posted: Jul 11, 2007
Start date: Nov 2007
Primary completion: Dec 2016
Completion: Dec 2016
Results posted: Mar 1, 2017
Last update: Mar 29, 2017

Study contacts

Karen Reckamp

principal investigator · City of Hope Medical Center

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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