Pemetrexed Disodium or Erlotinib Hydrochloride as Second-Line Therapy in Treating Patients With Advanced Non-small Cell Lung Cancer

Stage IV Non-Small Cell Lung Cancer Clinical Trial

— MARVEL  

Official title:

MARVEL: Marker Validation of Erlotinib in Lung Cancer- A Phase III Biomarker Validation Study of Second-Line Therapy in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) Randomized to Pemetrexed Versus Erlotinib

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00738881
• Other study ID #: NCI-2009-00663
• Secondary ID: NCI-2009-00663CD
• Status: Terminated
• Phase: Phase 3
• First received: August 20, 2008
• Last updated: October 6, 2015
• Start date: October 2008
• Est. completion date: December 2014

Study information

• Verified date: December 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies pemetrexed disodium to see how well it works compared with erlotinib hydrochloride as second-line therapy in treating patients with non-small cell lung cancer that has spread to other places in the body. Pemetrexed disodium and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether pemetrexed disodium is more effective than erlotinib hydrochloride in treating advanced non-small cell lung cancer.

Description:

PRIMARY OBJECTIVES:

I. To evaluate whether there are differences in progression-free survival due to treatment with erlotinib (erlotinib hydrochloride) compared to pemetrexed (pemetrexed disodium) for subsets of previously treated non-small cell lung cancer (NSCLC) patients defined by epidermal growth factor receptor (EGFR)-fluorescent in situ hybridization (FISH) positive versus negativity.

SECONDARY OBJECTIVES:

I. Ascertain the presence or absence of true differences due to treatment in the objective clinical endpoints of overall survival, confirmed response rate, and adverse event profile for subsets of patients defined on the basis of the epidermal growth factor receptor (EGFR)-FISH positivity versus negativity.

II. Ascertain the presence or absence of true differences due to treatment in objective clinical endpoints (i.e., progression free survival, overall survival, confirmed response rate, and adverse event profile) for subsets of patients defined on the basis of the epidermal growth factor receptor (EGFR) expression as measured by immunohistochemistry (IHC).

III. Ascertain the presence or absence of true differences due to treatment in objective clinical endpoints (i.e., progression free survival, overall survival, confirmed response rate, and adverse event profile) for subsets of patients defined on the basis of the epidermal growth factor receptor (EGFR) gene mutation status (MUT).

IV. To evaluate the prognostic effect of EGFR copy number as measured by FISH separately by treatment arm, i.e., is there a difference in outcome for FISH(+) patients receiving erlotinib compared to FISH (-) patients receiving erlotinib, and similarly is there a difference in outcome for FISH(+) patients receiving pemetrexed compared to FISH (-) patients receiving pemetrexed.

V. To evaluate the prognostic effect of EGFR expression as measured by IHC separately by treatment arm, i.e., is there a difference in outcome for IHC(+) patients receiving erlotinib compared to IHC (-) patients receiving erlotinib, and similarly is there a difference in outcome for IHC(+) patients receiving pemetrexed compared to IHC (-)patients receiving pemetrexed.

VI. To evaluate the prognostic effect of EGFR mutation status separately by treatment arm, i.e., is there a difference in outcome for MUT(+) patients receiving erlotinib compared to MUT(-) patients receiving erlotinib, and similarly is there a difference in outcome for MUT(+) patients receiving pemetrexed compared to MUT(-) patients receiving pemetrexed.

VII. To prospectively test the hypothesis that functionally relevant polymorphisms in the genes encoding for pemetrexed targets, as well as genes encoding for one or more of the key enzymes involved in the transport, activation, and inactivation of pemetrexed, either singly or in combination, play a role in the efficacy and/or toxicity of pemetrexed.

VIII. To prospectively test the hypothesis that functionally relevant polymorphisms in the EGFR gene as well as genes encoding for one or more of the key enzymes involved in the metabolism of erlotinib, either singly or in combination, play a role in the efficacy and/or toxicity of erlotinib.

IX. Evaluate proteomic signatures in blood samples as predictors of survival and response to treatment with erlotinib.

X. To evaluate expression of thymidylate synthase, dihydrofolate reductase, phosphoribosylglycineamide (GAR) formyltransferase, and methylthioadenosine phosphorylase gene expression in tumor samples, as measured by IHC or quantitative polymerase chain reaction, as predictors of survival and response to treatment with pemetrexed.

XI. To evaluate proteomic signatures in blood samples of patients as predictors of response and survival to treatment with erlotinib.

XII. To evaluate the following variables measured in tumor samples, as predictors of response and survival to treatment with pemetrexed: Expression of thymidylate synthase, dihydrofolate reductase and GAR formyltransferase genes methylthioadenosine phosphorylase expression by IHC or quantitative polymerase chain reaction (PCR).

XIII. To evaluate the following variables measured in tumor samples, as predictors of response and survival to treatment with erlotinib: Rat sarcoma (Ras) mutational status, EGFR mutational status and, epithelial to mesenchymal transition (EMT) status (measured by E-cadherin expression and vimentin expression) by IHC.

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

ARM I: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive pemetrexed disodium intravenously (IV) over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: December 2014
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented recurrence or disease progression of NSCLC

• NSCLC must be confirmed by pathologic examination, either on initial diagnosis or disease recurrence/progression; mixed histology allowed if all components consistent with NSCLC

• Measurable disease, defined as at least one lesion whose longest diameter can be accurately measured as >= 2.0 cm by conventional techniques or as >= 1.0 cm by spiral computed tomography (CT); if spiral CT is used, it must be used for both pre- and post- treatment tumor assessments

• Prior radiation therapy is permitted as long as:

• Recovered from the toxic effects of radiation treatment before study entry, except for alopecia

• =< 25% of bone marrow radiated

• Presence of measurable disease whether in-field disease progression/recurrence or disease outside the treatment fields of radiation port

• Absolute neutrophil count (ANC) >= 1,500 uL

• Platelet (PLT) >= 100,000 uL

• Hemoglobin (Hgb) >= 10 g/dL

• Total bilirubin: within normal institutional limits (WNL) OR direct bilirubin =< upper limit of normal (ULN)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

• International normalized ratio (INR) =< 1.5

• Calculated creatinine clearance >= 45 mL/min using the Cockcroft-Gault formula

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

• Negative pregnancy test done =< 7 days prior to pre-registration, for women of childbearing potential only

• Ability to provide informed consent

• Life expectancy >= 12 weeks

• Tissue available and willing to submit tissue for central pathology review and EGFR evaluation; performed on original diagnostic/recurrent tissue (preferably paraffin-embedded tissue blocks); if institution unable to release tissue blocks, willing to submit 25 unstained slides (15 sections cut at 5 microns mounted on charged slides and 10 sections cut at 10 microns mounted on uncharged slides)

• Must be previously treated for advanced disease with only 1 chemotherapy regimen which must contain cytotoxic agent(s); adjuvant/neoadjuvant treatment with cytotoxic agent(s) administered < 12 months (from date chemotherapy was started) prior to pre-registration will be considered as one prior treatment; NOTE: adjuvant/neoadjuvant treatment administered >= 12 months, use of targeted agents such as monoclonal antibodies prior to pre-registration will NOT be counted as one prior treatment; patient could have had adjuvant/neoadjuvant chemotherapy >= 12 months and 1 systemic chemotherapy regimen for metastatic or recurrent disease

• Able to take folic acid, vitamin B12 supplementation, and dexamethasone

• Able to permanently discontinue aspirin dose of >= 1.3 grams/day >= 10 days before and after pemetrexed treatment

• Fertile patients must use effective contraception

• Able to take folic acid, vitamin B_12 supplementation, and dexamethasone

• Stable brain metastasis that have been treated with either whole brain radiation therapy or gamma knife surgery and are off steroid treatment for > 14 days prior to pre-registration, if applicable

• Willingness to return to enrolling institution for treatment and follow-up

Exclusion Criteria:

• Any of the following:

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequate contraception

• Any clinically significant infection, at the treating physician's discretion

• Known human immunodeficiency virus (HIV) positive patients

• Impairment of gastrointestinal (GI) function, inability to swallow pills in the absence of a feeding tube, or GI disease that may significantly alter absorption of oral medications (e.g. ulcerative disease, uncontrolled nausea and vomiting, malabsorption syndromes, bowel obstruction, etc)

• Serious condition that, in the opinion of the investigator, would compromise the patient's ability to complete the study or increase the risk for serious adverse events

• Any of the following prior therapies:

• Prior radiation to > 25% of bone marrow

• EGFR tyrosine kinase inhibitors

• Pemetrexed

• Chemotherapy =< 3 weeks prior to pre-registration

• Mitomycin C/nitrosoureas =< 6 weeks prior to pre-registration

• Immunotherapy =< 2 weeks prior to pre-registration

• Biologic therapy =< 2 weeks prior to pre-registration

• Gene therapy =< 2 weeks prior to pre-registration

• Full field radiation therapy =< 4 weeks prior to pre-registration

• Limited field radiation therapy =< 2 weeks prior to pre-registration

• Major surgery (i.e., laparotomy), open biopsy, or significant traumatic injury =< 4 weeks prior to pre-registration or anticipation of need for major surgical procedure during the course of the study; minor surgery =< 2 weeks prior to pre-registration; insertion of a vascular access device is not considered major or minor surgery in this regard

• Other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) =< 4 weeks prior to pre-registration

• Steroid therapy for brain metastasis =< 14 days prior to pre-registration

• Symptomatic serosal effusion (>= Common Terminology Criteria for Adverse Events [CTCAE] v3.0 grade 2 dyspnea) that is not amenable to drainage prior to pre-registration

• Other invasive solid or hematologic malignancy; exceptions: prior malignancy was diagnosed and definitively treated >= 5 years previously with no subsequent evidence of recurrence; patients with a history of low-grade (Gleason score =< 6) localized prostate cancer will be eligible even if diagnosed < 3 years prior to pre-registration; these patients may continue on medications concomitantly to maintain their disease remission as necessary; patients with carcinoma in situ, regardless of organ involvement, or non-melanoma cutaneous carcinomas are eligible if these were definitively treated >= 3 years previously with no subsequent evidence of recurrence; Note: patients with breast cancer that was definitively treated > 5 years earlier but continue to receive aromatase inhibitors are NOT eligible

• Only non-measurable disease, defined as all other lesions, including small lesions whose longest diameter measures < 2 cm with conventional techniques or < 1.0 cm with spiral CT, and truly non-measurable lesions, which include the following as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria dated June 1999:

• Bone lesions

• Leptomeningeal disease

• Ascites

• Pleural/pericardial effusion

• Inflammatory breast disease

• Lymphangitis cutis/pulmonis

• Abdominal masses that are not confirmed and followed by imaging techniques

• Cystic lesions

• Single disease site in prior radiation field

• Any of the following concurrent severe and/or uncontrolled medical conditions:

• Angina pectoris

• History of congestive heart failure =< 3 months prior to pre-registration, unless ejection fraction > 40%

• Myocardial infarction =< 6 months prior to pre-registration

• Cardiac arrhythmia

• Diabetes mellitus

• Hypertension

• Any other severe underlying diseases which are, in the judgment of the investigator, inappropriate for entry into this study

• Respiratory symptoms > CTCAE grade 1

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Recurrent Non-Small Cell Lung Carcinoma
• Stage IIIA Non-Small Cell Lung Cancer
• Stage IIIB Non-Small Cell Lung Cancer
• Stage IV Non-Small Cell Lung Cancer

Intervention

Drug:
• Erlotinib Hydrochloride
Given PO
• Pemetrexed Disodium
Given IV

Locations

Country	Name	City	State
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa
United States	AnMed Health Hospital	Anderson	South Carolina
United States	Michigan Cancer Research Consortium CCOP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Hospital District Sixth of Harper County	Anthony	Kansas
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Franciscan St. Francis Health-Beech Grove	Beech Grove	Indiana
United States	MacNeal Hospital and Cancer Center	Berwyn	Illinois
United States	Hematology Oncology Associates-Quad Cities	Bettendorf	Iowa
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Frontier Cancer Center and Blood Institute-Billings	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Mid Dakota Clinic	Bismarck	North Dakota
United States	Saint Alexius Medical Center	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Boca Raton Comprehensive Cancer Center	Boca Raton	Florida
United States	Lynn Regional Cancer Center - West	Boca Raton	Florida
United States	Boston Medical Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Steward Saint Elizabeth's Medical Center	Brighton	Massachusetts
United States	Bristol Hospital	Bristol	Connecticut
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Graham Hospital Association	Canton	Illinois
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Cedar Rapids Oncology Association	Cedar Rapids	Iowa
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	North Coast Cancer Care-Clyde	Clyde	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Danville Regional Medical Center	Danville	Virginia
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Genesis Medical Center - East Campus	Davenport	Iowa
United States	Genesis Medical Center - West Campus	Davenport	Iowa
United States	Dayton CCOP	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Colorado Cancer Research Program CCOP	Denver	Colorado
United States	Exempla Saint Joseph Hospital	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa Oncology Research Association CCOP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Capitol	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey
United States	The Memorial Hospital at Easton	Easton	Maryland
United States	Hematology Oncology Center Incorporated	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Hunterdon Medical Center	Flemington	New Jersey
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Sparks Regional Medical Center	Fort Smith	Arkansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Illinois CancerCare Galesburg	Galesburg	Illinois
United States	Illinois CancerCare-Cottage	Galesburg	Illinois
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Wayne Hospital	Greenville	Ohio
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Northern Montana Hospital	Havre	Montana
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois
United States	Hopedale Medical Complex - Hospital	Hopedale	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cape Cod Hospital	Hyannis	Massachusetts
United States	Allegiance Health	Jackson	Michigan
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Midwest Center for Hematology Oncology	Joliet	Illinois
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Joseph Health Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Truman Medical Center	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Sparrow Hospital	Lansing	Michigan
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Liberty Hospital	Liberty	Missouri
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	NorthShore Hematology Oncology-Libertyville	Libertyville	Illinois
United States	Lima Memorial Hospital	Lima	Ohio
United States	Meeker County Memorial Hospital	Litchfield	Minnesota
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Memorial Hospital Of Martinsville	Martinsville	Virginia
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Saint Luke's Hospital	Maumee	Ohio
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Middlesex Hospital	Middletown	Connecticut
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Minnesota Cooperative Group Outreach Program	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Community Medical Hospital	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Holy Family Medical Center	Monmouth	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County	Mount Holly	New Jersey
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	DuPage Medical Group-Ogden	Naperville	Illinois
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Illinois CancerCare-Community Cancer Center	Normal	Illinois
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Pekin Cancer Treatment Center	Pekin	Illinois
United States	Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois Oncology Research Association CCOP	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CC	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Valley Care Health System - Pleasanton	Pleasanton	California
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Riverview Medical Center/Booker Cancer Center	Red Bank	New Jersey
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Hospital and Health Care Services	Richmond	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Cancer Trials Support Unit	Rockville	Maryland
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Center for Cancer Care and Research	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis University Hospital	Saint Louis	Missouri
United States	Regions Hospital	Saint Paul	Minnesota
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Mercy Hospital	Scranton	Pennsylvania
United States	Scranton Hematology Oncology	Scranton	Pennsylvania
United States	Shawnee Mission Medical Center-KCCC	Shawnee Mission	Kansas
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	Saint Margaret's Hospital	Spring Valley	Illinois
United States	Memorial Medical Center	Springfield	Illinois
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Flower Hospital	Sylvania	Ohio
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Syracuse Veterans Administration Medical Center	Syracuse	New York
United States	North Suburban Medical Center	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Saint Anne Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Stormont-Vail Regional Health Center	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	Tahoe Forest Cancer Center	Truckee	California
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Virtua West Jersey Hospital Voorhees	Voorhees	New Jersey
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Covenant Medical Center	Waterloo	Iowa
United States	Fulton County Health Center	Wauseon	Ohio
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Southeast Cancer Consortium-Upstate NCORP	Winston-Salem	North Carolina
United States	Metro Health Hospital	Wyoming	Michigan
United States	Greene Memorial Hospital	Xenia	Ohio

Sponsors (5)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Canadian Cancer Trials Group, Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, Southwest Oncology Group

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	Estimated using the method of Kaplan-Meier survival curves to compare PFS between the erlotinib and pemetrexed arms using an intent-to-treat (ITT) analysis. Due to the small sample size (21 of the required 954 patients ~2%), analyses within the FISH(+) and FISH(-) groups were not performed, and no formal analyses for the primary or the secondary efficacy outcomes were performed.	Time from randomization to the first date of documented disease progression or death, assessed up to 5 years	No
Secondary	Time to Treatment Failure	The distribution of all time to event data will be estimated using the method of Kaplan-Meier survival curves.	The time from date of randomization to the date at which the patient is removed from the treatment, assessed up to 5 years	No
Secondary	Overall Survival	Will be estimated using the method of Kaplan-Meier survival curves. A 1-sided stratified log rank test [accounting for all the stratification factors except FISH status and cooperative group] will be used to compare overall survival between the erlotinib and pemetrexed arms within the FISH(+) and FISH(-) subgroups, compare overall and progression free survival between the erlotinib and pemetrexed arms within the subgroups defined on the basis of the epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC), and EGFR gene mutation status (MUT). Cox proportional hazards model will be used to assess potential differences.	Time from randomization to time of death from any cause, assessed up to 5 years	No
Secondary	Confirmed Response Rate Defined as Complete Response (CR) or a Partial Response (PR) Per Response Evaluation Criteria In Solid Tumors (RECIST)	Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. The proportion of patients with confirmed CR and PR will be computed within each treatment arm and exact binomial confidence intervals for the true proportion computed. Chi-square test and Fisher's exact test will be used to compare the response rates between the treatment arms within the subgroups defined by FISH status, IHC, and MUT.	Up to 5 years	No