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

Recurrent Non-Small Cell Lung Carcinoma Clinical Trial

Official title:

A Randomized Phase II Study to Assess the Efficacy of Pemetrexed or Sunitinib (NSC # 736511) or Pemetrexed Plus Sunitinib in the Second-Line Treatment of Advanced Non-small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00698815
• Other study ID #: NCI-2009-00471
• Secondary ID: NCI-2009-00471CD
• Status: Completed
• Phase: Phase 2
• Start date: April 15, 2008

Study information

• Verified date: January 2022
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 130
• Est. primary completion date: December 1, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Pemetrexed Disodium
Given IV
• Sunitinib Malate
Given PO

Locations

Country	Name	City	State
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	Arroyo Grande Community	Arroyo Grande	California
United States	Randolph Hospital	Asheboro	North Carolina
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	University of Vermont College of Medicine	Burlington	Vermont
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Jesse Brown Veterans Affairs Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Danville Regional Medical Center	Danville	Virginia
United States	Greenville Health System Cancer Institute-Easley	Easley	South Carolina
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Exeter Hospital	Exeter	New Hampshire
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Kaiser Permanente Hospital	Fontana	California
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Valley Medical Oncology Consultants-Fremont	Fremont	California
United States	Glens Falls Hospital	Glens Falls	New York
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Butternut	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Greenville Health System Cancer Institute-Greer	Greer	South Carolina
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	Hartford Hospital	Hartford	Connecticut
United States	Saint Mary's Medical Center	Huntington	West Virginia
United States	Iowa City VA Healthcare System	Iowa City	Iowa
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Capital Region Medical Center-Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois
United States	Jupiter Medical Center	Jupiter	Florida
United States	Kinston Medical Specialists PA	Kinston	North Carolina
United States	Community Howard Regional Health	Kokomo	Indiana
United States	AMITA Health Adventist Medical Center	La Grange	Illinois
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	LRGHealthcare-Lakes Region General Hospital	Laconia	New Hampshire
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Beebe Medical Center	Lewes	Delaware
United States	Nebraska Cancer Research Center	Lincoln	Nebraska
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente-Cadillac	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Memorial Hospital Of Martinsville	Martinsville	Virginia
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Middlesex Hospital	Middletown	Connecticut
United States	Dana-Farber/Brigham and Women's Cancer Center at Milford Regional	Milford	Massachusetts
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	El Camino Hospital	Mountain View	California
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	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Newton-Wellesley Hospital	Newton	Massachusetts
United States	Lakeland Community Hospital	Niles	Michigan
United States	Great Plains Regional Medical Center	North Platte	Nebraska
United States	Norwalk Hospital	Norwalk	Connecticut
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Hematology and Oncology Associates-Oakland	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Tom K Lee Inc	Oakland	California
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	Memorial Hospital of Rhode Island	Pawtucket	Rhode Island
United States	PCR Oncology	Pismo Beach	California
United States	Valley Care Health System - Pleasanton	Pleasanton	California
United States	Valley Medical Oncology Consultants	Pleasanton	California
United States	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Kaiser Permanente-Riverside	Riverside	California
United States	Lakeland Hospital	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Center for Cancer Care and Research	Saint Louis	Missouri
United States	Comprehensive Cancer Care PC	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Kaiser Permanente-San Diego Mission	San Diego	California
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	University of California San Diego	San Diego	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California
United States	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
United States	Iredell Memorial Hospital	Statesville	North Carolina
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	Marion L Shepard Cancer Center at Vidant Beaufort Hospital	Washington	North Carolina
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Michiana Hematology Oncology PC-Westville	Westville	Indiana
United States	New Hanover Regional Medical Center/Zimmer Cancer Center	Wilmington	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Kaiser Permanente	Woodland Hills	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	18 Week Progression-free Survival (PFS) Rate	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.	At 18 weeks
Secondary	PFS	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.	Time from randomization to disease progression and death of any cause, whichever comes first (up to 3 years)
Secondary	Overall Response Rate	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.	Duration of treatment (up to 3 years)
Secondary	Overall Survival (OS)	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.	Time from randomization to death (up to 3 years)