Pemetrexed and/or Sunitinib as Second-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer

NCT ID: NCT00698815

Last Updated: 2022-02-08

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-04-15

Brief Summary

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This randomized phase II trial studies pemetrexed disodium and sunitinib malate to compare how well they work when given alone or together as second-line therapy in treating patients with stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether pemetrexed disodium and sunitinib malate are more effective when given alone or together in treating non-small cell lung cancer.

Detailed Description

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PRIMARY OBJECTIVES:

I. To estimate the 18 week progression-free survival rate of pemetrexed (pemetrexed disodium) alone (Arm I), sunitinib (sunitinib malate) alone (Arm II) and pemetrexed plus sunitinib (Arm III) in the second-line setting of advanced non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To compare the progression-free survival of the three arms. II. To estimate the response rate, duration of response, rate of stable disease, overall survival and to characterize the toxicity profiles of the three arms.

III. To estimate the response rate, duration of response, rate of stable disease, overall survival and toxicity of sunitinib in those patients on Arm I that receive this regimen in the third line setting.

IV. To assess vascular endothelial growth factor (VEGF) haplotypes in advanced non-small cell lung cancer.

V. To test change in tumor size at 6 weeks (after 2 cycles of therapy, typically the first evaluation point in this type of study) as an early predictor of therapeutic activity in second-line treatment of non-small cell lung cancer.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: 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. Patients with documented disease progression may then receive sunitinib malate as in Arm II as third-line therapy.

ARM II: Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in Arm I as third-line therapy.

ARM III: Patients receive pemetrexed disodium IV over 10 minutes on day 1 and sunitinib malate PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.

After completion of study treatment, patients are followed up every 6 weeks until disease progression and then every 6 months for 2 years.

Conditions

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Recurrent Non-Small Cell Lung Carcinoma Stage IIIB Non-Small Cell Lung Cancer AJCC v7 Stage IV Non-Small Cell Lung Cancer AJCC v7

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I (pemetrexed)

Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in Arm II as third-line therapy.

Group Type EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pemetrexed Disodium

Intervention Type DRUG

Given IV

Arm II (sunitinib)

Patients receive sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in Arm I as third-line therapy.

Group Type EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Sunitinib Malate

Intervention Type DRUG

Given PO

Arm III (pemetrexed and sunitinib)

Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.

Group Type EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pemetrexed Disodium

Intervention Type DRUG

Given IV

Sunitinib Malate

Intervention Type DRUG

Given PO

Interventions

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Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pemetrexed Disodium

Given IV

Intervention Type DRUG

Sunitinib Malate

Given PO

Intervention Type DRUG

Other Intervention Names

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Alimta LY231514 N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt SU011248 SU11248 sunitinib Sutent

Eligibility Criteria

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Inclusion Criteria

* Histologic documentation: histologic or cytologic documentation of NSCLC
* Stage: IIIB/IV with evidence of disease progression following first-line therapy
* Tumor site: lung (non-small cell)
* No cavitary lesions
* Only one prior chemotherapy regimen in the first-line stage IIIB/IV setting is allowed; this could have been either a platinum- or non-platinum-based regimen
* First-line therapy must be completed \>= 28 days before registration
* Prior adjuvant therapy is allowed provided the patient had one previous regimen in the advanced stage IIIB/IV setting
* At least 28 days from prior major surgery and at least 14 days from any prior radiotherapy before registration
* No prior inhibitors of VEGF receptor (VEGFR) (e.g., SU5416, SU6668, AZ6474, SU11248, PTK787, AZD2171, AEE-788, sorafenib); prior treatment with epidermal growth factor receptor (EGFR) inhibitors and bevacizumab is allowed, provided at least 4 weeks has elapsed
* No prior pemetrexed
* Patients must have measurable or non-measurable disease

* Measurable disease

* Lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 2 cm with conventional techniques or as \>= 1 cm with spiral computed tomography (CT) scan
* Non-measurable disease

* All other lesions, including small lesions (longest diameter \< 20 mm with conventional techniques or \< 10 mm with spiral CT scan) and truly nonmeasurable lesions
* Lesions that are considered non-measurable include the following:

* Bone lesions
* Leptomeningeal disease
* Ascites
* Pleural/pericardial effusion
* Lymphangitis cutis/pulmonis
* Abdominal masses that are not confirmed and followed by imaging techniques
* Cystic lesions
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Pregnant or nursing mothers are not eligible for this study; patients in their child bearing years must have a baseline negative pregnancy test (in the case of females); males and females must practice appropriate contraceptive measures during the period of protocol therapy and for 6 months after completion of protocol therapy; appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives (Norplant), or double barrier method (diaphragm plus condom)
* No ongoing cardiac dysrhythmias, atrial fibrillation, or history of corrected QT interval (QTc interval) \> 500 msec (within 2 years prior to registration); the use of agents with proarrhythmic potential (e.g., quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, flecainide) is not recommended while on protocol therapy
* Patients with class I New York Heart Association (NYHA) heart failure are eligible; patients with a history of class II NYHA heart failure are eligible, provided they meet at least one of the following criteria:

* Patients with a history of class II heart failure who are asymptomatic on treatment
* Patients with prior anthracycline exposure
* Patients who have received central thoracic radiation that included the heart in the radiotherapy port
* Patients with a history of symptomatic congestive heart failure within 12 months prior to entry are not eligible
* No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft or stenting, cerebrovascular accident or transient ischemic attack within the last year
* Patients with hypertension that cannot be controlled by medications (\> 150/100 mmHg despite optimal medical therapy) are not eligible
* Patients who require use of therapeutic anticoagulation for thromboembolic disease are not eligible; Note: low doses of Coumadin (up to 2 mg daily) are permitted for prophylaxis of thrombosis
* No history of venous thrombosis, pulmonary embolism, or hypercoagulopathy syndrome
* No history of pulmonary hemorrhage, bleeding diathesis, or evidence of hemoptysis; patients with blood-tinged or blood-streaked sputum will be permitted on study if the hemoptysis amounts to less than 5 mL of blood per episode and less than 10 mL of blood per 24-hour period in the best estimate of the investigator
* Patients with a history of hypothyroidism or hyperthyroidism are eligible, provided they are currently euthyroid
* None of the following within 28 days of beginning treatment: abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, serious or non-healing wound, ulcer, or bone fracture
* The use of the following specific inhibitors and inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) is not permitted; the following inhibitors of CYP3A4 are prohibited within 7 days before and during treatment with sunitinib: azole antifungals (ketoconazole, itraconazole), diltiazem, clarithromycin, erythromycin, verapamil, delavirdine, and human immunodeficiency virus (HIV) protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir); the following inducers of CYP3A4 are prohibited within 12 days before beginning and during treatment with sunitinib: rifampin, rifabutin, carbamazepine, phenobarbital, phenytoin, St. John's Wort, efavirenz, tipranavir

* Other inhibitors and inducers of CYP3A4 may be used if necessary, but their use is discouraged
* No symptomatic or untreated central nervous system (CNS) metastases; patients with CNS metastases must be asymptomatic, must have received definitive therapy (\>= 6 weeks since resection or \>= 2 weeks since radiotherapy) for brain metastases, and be off steroids or on a stable dose for 2 weeks prior to registration
* No chronic daily treatment with aspirin (\> 325 mg/day) or non-steroidal antiinflammatory agents known to inhibit platelet function; treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal) is not allowed
* No pleural effusions or ascites that are detectable on physical exam
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rebecca Heist

Role: PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Locations

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Kaiser Permanente-Anaheim

Anaheim, California, United States

Site Status

Arroyo Grande Community

Arroyo Grande, California, United States

Site Status

Kaiser Permanente-Baldwin Park

Baldwin Park, California, United States

Site Status

Kaiser Permanente-Bellflower

Bellflower, California, United States

Site Status

East Bay Radiation Oncology Center

Castro Valley, California, United States

Site Status

Eden Hospital Medical Center

Castro Valley, California, United States

Site Status

Valley Medical Oncology Consultants-Castro Valley

Castro Valley, California, United States

Site Status

Bay Area Breast Surgeons Inc

Emeryville, California, United States

Site Status

Kaiser Permanente Hospital

Fontana, California, United States

Site Status

Valley Medical Oncology Consultants-Fremont

Fremont, California, United States

Site Status

Kaiser Permanente - Harbor City

Harbor City, California, United States

Site Status

Kaiser Permanente-Irvine

Irvine, California, United States

Site Status

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Site Status

Kaiser Permanente-Cadillac

Los Angeles, California, United States

Site Status

Contra Costa Regional Medical Center

Martinez, California, United States

Site Status

El Camino Hospital

Mountain View, California, United States

Site Status

Highland General Hospital

Oakland, California, United States

Site Status

Alta Bates Summit Medical Center - Summit Campus

Oakland, California, United States

Site Status

Bay Area Tumor Institute

Oakland, California, United States

Site Status

Hematology and Oncology Associates-Oakland

Oakland, California, United States

Site Status

Tom K Lee Inc

Oakland, California, United States

Site Status

Kaiser Permanente - Panorama City

Panorama City, California, United States

Site Status

PCR Oncology

Pismo Beach, California, United States

Site Status

Valley Care Health System - Pleasanton

Pleasanton, California, United States

Site Status

Valley Medical Oncology Consultants

Pleasanton, California, United States

Site Status

Kaiser Permanente-Riverside

Riverside, California, United States

Site Status

University of California San Diego

San Diego, California, United States

Site Status

Kaiser Permanente-San Diego Mission

San Diego, California, United States

Site Status

Kaiser Permanente-San Diego Zion

San Diego, California, United States

Site Status

Kaiser Permanente-San Marcos

San Marcos, California, United States

Site Status

Doctors Medical Center- JC Robinson Regional Cancer Center

San Pablo, California, United States

Site Status

Kaiser Permanente

Woodland Hills, California, United States

Site Status

Hartford Hospital

Hartford, Connecticut, United States

Site Status

Middlesex Hospital

Middletown, Connecticut, United States

Site Status

Norwalk Hospital

Norwalk, Connecticut, United States

Site Status

Beebe Medical Center

Lewes, Delaware, United States

Site Status

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Site Status

Jupiter Medical Center

Jupiter, Florida, United States

Site Status

Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

Jesse Brown Veterans Affairs Medical Center

Chicago, Illinois, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Joliet Oncology-Hematology Associates Limited

Joliet, Illinois, United States

Site Status

AMITA Health Adventist Medical Center

La Grange, Illinois, United States

Site Status

Elkhart Clinic

Elkhart, Indiana, United States

Site Status

Michiana Hematology Oncology PC-Elkhart

Elkhart, Indiana, United States

Site Status

Elkhart General Hospital

Elkhart, Indiana, United States

Site Status

Community Howard Regional Health

Kokomo, Indiana, United States

Site Status

IU Health La Porte Hospital

La Porte, Indiana, United States

Site Status

Michiana Hematology Oncology PC-Mishawaka

Mishawaka, Indiana, United States

Site Status

Saint Joseph Regional Medical Center-Mishawaka

Mishawaka, Indiana, United States

Site Status

Michiana Hematology Oncology PC-Plymouth

Plymouth, Indiana, United States

Site Status

Memorial Hospital of South Bend

South Bend, Indiana, United States

Site Status

Michiana Hematology Oncology PC-South Bend

South Bend, Indiana, United States

Site Status

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

Site Status

Michiana Hematology Oncology PC-Westville

Westville, Indiana, United States

Site Status

University of Iowa Healthcare Cancer Services Quad Cities

Bettendorf, Iowa, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

Iowa City VA Healthcare System

Iowa City, Iowa, United States

Site Status

Harold Alfond Center for Cancer Care

Augusta, Maine, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

Union Hospital of Cecil County

Elkton, Maryland, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Dana-Farber/Brigham and Women's Cancer Center at Milford Regional

Milford, Massachusetts, United States

Site Status

Newton-Wellesley Hospital

Newton, Massachusetts, United States

Site Status

Lakeland Community Hospital

Niles, Michigan, United States

Site Status

Lakeland Hospital

Saint Joseph, Michigan, United States

Site Status

Marie Yeager Cancer Center

Saint Joseph, Michigan, United States

Site Status

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

University of Missouri - Ellis Fischel

Columbia, Missouri, United States

Site Status

Capital Region Medical Center-Goldschmidt Cancer Center

Jefferson City, Missouri, United States

Site Status

Missouri Baptist Medical Center

St Louis, Missouri, United States

Site Status

Center for Cancer Care and Research

St Louis, Missouri, United States

Site Status

Comprehensive Cancer Care PC

St Louis, Missouri, United States

Site Status

CHI Health Saint Francis

Grand Island, Nebraska, United States

Site Status

Nebraska Cancer Research Center

Lincoln, Nebraska, United States

Site Status

Great Plains Regional Medical Center

North Platte, Nebraska, United States

Site Status

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Site Status

Alegent Health Immanuel Medical Center

Omaha, Nebraska, United States

Site Status

Alegent Health Bergan Mercy Medical Center

Omaha, Nebraska, United States

Site Status

Creighton University Medical Center

Omaha, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States

Site Status

Nevada Cancer Research Foundation CCOP

Las Vegas, Nevada, United States

Site Status

Exeter Hospital

Exeter, New Hampshire, United States

Site Status

LRGHealthcare-Lakes Region General Hospital

Laconia, New Hampshire, United States

Site Status

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Site Status

Hematology Oncology Associates of Central New York-East Syracuse

East Syracuse, New York, United States

Site Status

Glens Falls Hospital

Glens Falls, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

Northwell Health/Center for Advanced Medicine

New Hyde Park, New York, United States

Site Status

State University of New York Upstate Medical University

Syracuse, New York, United States

Site Status

Syracuse Veterans Administration Medical Center

Syracuse, New York, United States

Site Status

Randolph Hospital

Asheboro, North Carolina, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Site Status

Wayne Memorial Hospital

Goldsboro, North Carolina, United States

Site Status

Cone Health Cancer Center

Greensboro, North Carolina, United States

Site Status

Kinston Medical Specialists PA

Kinston, North Carolina, United States

Site Status

Annie Penn Memorial Hospital

Reidsville, North Carolina, United States

Site Status

Iredell Memorial Hospital

Statesville, North Carolina, United States

Site Status

Marion L Shepard Cancer Center at Vidant Beaufort Hospital

Washington, North Carolina, United States

Site Status

New Hanover Regional Medical Center/Zimmer Cancer Center

Wilmington, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Memorial Hospital of Rhode Island

Pawtucket, Rhode Island, United States

Site Status

Greenville Health System Cancer Institute-Easley

Easley, South Carolina, United States

Site Status

McLeod Regional Medical Center

Florence, South Carolina, United States

Site Status

Saint Francis Hospital

Greenville, South Carolina, United States

Site Status

Greenville Health System Cancer Institute-Andrews

Greenville, South Carolina, United States

Site Status

Greenville Health System Cancer Institute-Butternut

Greenville, South Carolina, United States

Site Status

Greenville Health System Cancer Institute-Faris

Greenville, South Carolina, United States

Site Status

Greenville Memorial Hospital

Greenville, South Carolina, United States

Site Status

Greenville Health System Cancer Institute-Eastside

Greenville, South Carolina, United States

Site Status

Self Regional Healthcare

Greenwood, South Carolina, United States

Site Status

Greenville Health System Cancer Institute-Greer

Greer, South Carolina, United States

Site Status

Greenville Health System Cancer Institute-Seneca

Seneca, South Carolina, United States

Site Status

Greenville Health System Cancer Institute-Spartanburg

Spartanburg, South Carolina, United States

Site Status

Central Vermont Medical Center/National Life Cancer Treatment

Berlin Corners, Vermont, United States

Site Status

University of Vermont College of Medicine

Burlington, Vermont, United States

Site Status

Danville Regional Medical Center

Danville, Virginia, United States

Site Status

Memorial Hospital Of Martinsville

Martinsville, Virginia, United States

Site Status

Saint Mary's Medical Center

Huntington, West Virginia, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2009-00471

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000589102

Identifier Type: -

Identifier Source: secondary_id

CALGB 30704

Identifier Type: OTHER

Identifier Source: secondary_id

CALGB-30704

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00471

Identifier Type: -

Identifier Source: org_study_id

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