Pemetrexed and/or Sunitinib as Second-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer
- Conditions
- Recurrent Non-Small Cell Lung CarcinomaStage IIIB Non-Small Cell Lung Cancer AJCC v7Stage IV Non-Small Cell Lung Cancer AJCC v7
- Interventions
- Registration Number
- NCT00698815
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 130
-
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
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No history of venous thrombosis, pulmonary embolism, or hypercoagulopathy syndrome
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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
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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
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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
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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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (pemetrexed) Pemetrexed Disodium 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. Arm III (pemetrexed and sunitinib) Pemetrexed Disodium 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. Arm II (sunitinib) Laboratory Biomarker Analysis 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. Arm I (pemetrexed) Laboratory Biomarker Analysis 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. Arm III (pemetrexed and sunitinib) Laboratory Biomarker Analysis 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. Arm II (sunitinib) Sunitinib Malate 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. Arm III (pemetrexed and sunitinib) Sunitinib Malate 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.
- Primary Outcome Measures
Name Time Method 18 Week Progression-free Survival (PFS) Rate At 18 weeks The 18 week progression-free survival rate was defined as the proportion of patients that were alive and progression-free 18 weeks after registration into the study. Disease progression was assessed per modified RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, in either primary or nodal lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of new lesions. Kaplan-Meier estimate of 18-week progression-free survival was calculated.
- Secondary Outcome Measures
Name Time Method PFS Time from randomization to disease progression and death of any cause, whichever comes first (up to 3 years) PFS was defined as the time from randomization until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. Progression is defined as in the primary outcome measure.
Overall Response Rate Duration of treatment (up to 3 years) The proportion of patients who respond (completely or partially) to each combination regimen will be estimated. An exact binomial confidence interval will be computed for these estimates.
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions.Overall Survival (OS) Time from randomization to death (up to 3 years) OS is defined as the time from patient randomization to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.
Trial Locations
- Locations (129)
University of Vermont College of Medicine
🇺🇸Burlington, Vermont, United States
Iredell Memorial Hospital
🇺🇸Statesville, North Carolina, United States
Greenville Health System Cancer Institute-Spartanburg
🇺🇸Spartanburg, South Carolina, United States
Kaiser Permanente-Riverside
🇺🇸Riverside, California, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
University of Iowa Healthcare Cancer Services Quad Cities
🇺🇸Bettendorf, Iowa, United States
Michiana Hematology Oncology PC-Westville
🇺🇸Westville, Indiana, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Iowa City VA Healthcare System
🇺🇸Iowa City, Iowa, United States
Union Hospital of Cecil County
🇺🇸Elkton, Maryland, United States
Great Plains Regional Medical Center
🇺🇸North Platte, Nebraska, United States
Harold Alfond Center for Cancer Care
🇺🇸Augusta, Maine, United States
Nebraska Cancer Research Center
🇺🇸Lincoln, Nebraska, United States
CHI Health Saint Francis
🇺🇸Grand Island, Nebraska, United States
Saint Francis Hospital
🇺🇸Greenville, South Carolina, United States
McLeod Regional Medical Center
🇺🇸Florence, South Carolina, United States
Greenville Health System Cancer Institute-Faris
🇺🇸Greenville, South Carolina, United States
LRGHealthcare-Lakes Region General Hospital
🇺🇸Laconia, New Hampshire, United States
Self Regional Healthcare
🇺🇸Greenwood, South Carolina, United States
Central Vermont Medical Center/National Life Cancer Treatment
🇺🇸Berlin, Vermont, United States
Greenville Health System Cancer Institute-Greer
🇺🇸Greer, South Carolina, United States
Greenville Health System Cancer Institute-Seneca
🇺🇸Seneca, South Carolina, United States
Greenville Health System Cancer Institute-Eastside
🇺🇸Greenville, South Carolina, United States
Greenville Health System Cancer Institute-Butternut
🇺🇸Greenville, South Carolina, United States
Saint Mary's Medical Center
🇺🇸Huntington, West Virginia, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Greenville Health System Cancer Institute-Easley
🇺🇸Easley, South Carolina, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Nevada Cancer Research Foundation CCOP
🇺🇸Las Vegas, Nevada, United States
Dana-Farber/Brigham and Women's Cancer Center at Milford Regional
🇺🇸Milford, Massachusetts, United States
University of California San Diego
🇺🇸San Diego, California, United States
Capital Region Medical Center-Goldschmidt Cancer Center
🇺🇸Jefferson City, Missouri, United States
Exeter Hospital
🇺🇸Exeter, New Hampshire, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
Syracuse Veterans Administration Medical Center
🇺🇸Syracuse, New York, United States
New Hanover Regional Medical Center/Zimmer Cancer Center
🇺🇸Wilmington, North Carolina, United States
Marion L Shepard Cancer Center at Vidant Beaufort Hospital
🇺🇸Washington, North Carolina, United States
Kinston Medical Specialists PA
🇺🇸Kinston, North Carolina, United States
Memorial Hospital of Rhode Island
🇺🇸Pawtucket, Rhode Island, United States
Greenville Health System Cancer Institute-Andrews
🇺🇸Greenville, South Carolina, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
Jesse Brown Veterans Affairs Medical Center
🇺🇸Chicago, Illinois, United States
Joliet Oncology-Hematology Associates Limited
🇺🇸Joliet, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
AMITA Health Adventist Medical Center
🇺🇸La Grange, Illinois, United States
Elkhart General Hospital
🇺🇸Elkhart, Indiana, United States
IU Health La Porte Hospital
🇺🇸La Porte, Indiana, United States
Lakeland Hospital
🇺🇸Saint Joseph, Michigan, United States
Michiana Hematology Oncology PC-Plymouth
🇺🇸Plymouth, Indiana, United States
Community Howard Regional Health
🇺🇸Kokomo, Indiana, United States
Northern Indiana Cancer Research Consortium
🇺🇸South Bend, Indiana, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Newton-Wellesley Hospital
🇺🇸Newton, Massachusetts, United States
Lakeland Community Hospital
🇺🇸Niles, Michigan, United States
Marie Yeager Cancer Center
🇺🇸Saint Joseph, Michigan, United States
Center for Cancer Care and Research
🇺🇸Saint Louis, Missouri, United States
University of Missouri - Ellis Fischel
🇺🇸Columbia, Missouri, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Northwell Health/Center for Advanced Medicine
🇺🇸New Hyde Park, New York, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Glens Falls Hospital
🇺🇸Glens Falls, New York, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
Hematology Oncology Associates of Central New York-East Syracuse
🇺🇸East Syracuse, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Randolph Hospital
🇺🇸Asheboro, North Carolina, United States
Annie Penn Memorial Hospital
🇺🇸Reidsville, North Carolina, United States
Cone Health Cancer Center
🇺🇸Greensboro, North Carolina, United States
Wayne Memorial Hospital
🇺🇸Goldsboro, North Carolina, United States
Greenville Memorial Hospital
🇺🇸Greenville, South Carolina, United States
Memorial Hospital Of Martinsville
🇺🇸Martinsville, Virginia, United States
Danville Regional Medical Center
🇺🇸Danville, Virginia, United States
Kaiser Permanente-Baldwin Park
🇺🇸Baldwin Park, California, United States
Kaiser Permanente-Anaheim
🇺🇸Anaheim, California, United States
Arroyo Grande Community
🇺🇸Arroyo Grande, California, United States
Kaiser Permanente-Bellflower
🇺🇸Bellflower, California, United States
Eden Hospital Medical Center
🇺🇸Castro Valley, California, United States
Bay Area Breast Surgeons Inc
🇺🇸Emeryville, California, United States
Kaiser Permanente Hospital
🇺🇸Fontana, California, United States
Tom K Lee Inc
🇺🇸Oakland, California, United States
Valley Medical Oncology Consultants-Fremont
🇺🇸Fremont, California, United States
Kaiser Permanente - Harbor City
🇺🇸Harbor City, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Highland General Hospital
🇺🇸Oakland, California, United States
Valley Care Health System - Pleasanton
🇺🇸Pleasanton, California, United States
Kaiser Permanente - Panorama City
🇺🇸Panorama City, California, United States
Bay Area Tumor Institute
🇺🇸Oakland, California, United States
Kaiser Permanente-San Diego Zion
🇺🇸San Diego, California, United States
PCR Oncology
🇺🇸Pismo Beach, California, United States
Kaiser Permanente-San Diego Mission
🇺🇸San Diego, California, United States
Doctors Medical Center- JC Robinson Regional Cancer Center
🇺🇸San Pablo, California, United States
Norwalk Hospital
🇺🇸Norwalk, Connecticut, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Middlesex Hospital
🇺🇸Middletown, Connecticut, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Alegent Health Immanuel Medical Center
🇺🇸Omaha, Nebraska, United States
Alegent Health Bergan Mercy Medical Center
🇺🇸Omaha, Nebraska, United States
Creighton University Medical Center
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Comprehensive Cancer Care PC
🇺🇸Saint Louis, Missouri, United States
Alta Bates Summit Medical Center - Summit Campus
🇺🇸Oakland, California, United States
Kaiser Permanente-Irvine
🇺🇸Irvine, California, United States
Kaiser Permanente-Cadillac
🇺🇸Los Angeles, California, United States
Kaiser Permanente-San Marcos
🇺🇸San Marcos, California, United States
Hematology and Oncology Associates-Oakland
🇺🇸Oakland, California, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Valley Medical Oncology Consultants-Castro Valley
🇺🇸Castro Valley, California, United States
East Bay Radiation Oncology Center
🇺🇸Castro Valley, California, United States
Contra Costa Regional Medical Center
🇺🇸Martinez, California, United States
Valley Medical Oncology Consultants
🇺🇸Pleasanton, California, United States
El Camino Hospital
🇺🇸Mountain View, California, United States
Kaiser Permanente
🇺🇸Woodland Hills, California, United States
Jupiter Medical Center
🇺🇸Jupiter, Florida, United States
Saint Joseph Regional Medical Center-Mishawaka
🇺🇸Mishawaka, Indiana, United States
Elkhart Clinic
🇺🇸Elkhart, Indiana, United States
Michiana Hematology Oncology PC-Elkhart
🇺🇸Elkhart, Indiana, United States
Michiana Hematology Oncology PC-Mishawaka
🇺🇸Mishawaka, Indiana, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
Michiana Hematology Oncology PC-South Bend
🇺🇸South Bend, Indiana, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
Beebe Medical Center
🇺🇸Lewes, Delaware, United States