Clinical trial NCT00698815: Pemetrexed and/or Sunitinib as Second-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Non-Small Cell Lung Carcinoma
Stage IIIB Non-Small Cell Lung Cancer AJCC v7
Stage IV Non-Small Cell Lung Cancer AJCC v7
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-06-17
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 18 Week Progression-free Survival (PFS) Rate
timeFrame: At 18 weeks
Secondary outcomes:
measure: PFS
timeFrame: Time from randomization to disease progression and death of any cause, whichever comes first (up to 3 years)
measure: Overall Response Rate
timeFrame: Duration of treatment (up to 3 years)
measure: Overall Survival (OS)
timeFrame: Time from randomization to death (up to 3 years)
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Kaiser Permanente-Anaheim
state: California
city: Arroyo Grande
country: United States
facility: Arroyo Grande Community
state: California
city: Baldwin Park
country: United States
facility: Kaiser Permanente-Baldwin Park
state: California
city: Bellflower
country: United States
facility: Kaiser Permanente-Bellflower
state: California
city: Castro Valley
country: United States
facility: East Bay Radiation Oncology Center
state: California
city: Castro Valley
country: United States
facility: Eden Hospital Medical Center
state: California
city: Castro Valley
country: United States
facility: Valley Medical Oncology Consultants-Castro Valley
state: California
city: Emeryville
country: United States
facility: Bay Area Breast Surgeons Inc
state: California
city: Fontana
country: United States
facility: Kaiser Permanente Hospital
state: California
city: Fremont
country: United States
facility: Valley Medical Oncology Consultants-Fremont
state: California
city: Harbor City
country: United States
facility: Kaiser Permanente - Harbor City
state: California
city: Irvine
country: United States
facility: Kaiser Permanente-Irvine
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente-Cadillac
state: California
city: Martinez
country: United States
facility: Contra Costa Regional Medical Center
state: California
city: Mountain View
country: United States
facility: El Camino Hospital
state: California
city: Oakland
country: United States
facility: Highland General Hospital
state: California
city: Oakland
country: United States
facility: Alta Bates Summit Medical Center - Summit Campus
state: California
city: Oakland
country: United States
facility: Bay Area Tumor Institute
state: California
city: Oakland
country: United States
facility: Hematology and Oncology Associates-Oakland
state: California
city: Oakland
country: United States
facility: Tom K Lee Inc
state: California
city: Panorama City
country: United States
facility: Kaiser Permanente - Panorama City
state: California
city: Pismo Beach
country: United States
facility: PCR Oncology
state: California
city: Pleasanton
country: United States
facility: Valley Care Health System - Pleasanton
state: California
city: Pleasanton
country: United States
facility: Valley Medical Oncology Consultants
state: California
city: Riverside
country: United States
facility: Kaiser Permanente-Riverside
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: San Diego
country: United States
facility: Kaiser Permanente-San Diego Mission
state: California
city: San Diego
country: United States
facility: Kaiser Permanente-San Diego Zion
state: California
city: San Marcos
country: United States
facility: Kaiser Permanente-San Marcos
state: California
city: San Pablo
country: United States
facility: Doctors Medical Center- JC Robinson Regional Cancer Center
state: California
city: Woodland Hills
country: United States
facility: Kaiser Permanente
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Middletown
country: United States
facility: Middlesex Hospital
state: Connecticut
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Jupiter
country: United States
facility: Jupiter Medical Center
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Chicago
country: United States
facility: Jesse Brown Veterans Affairs Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates Limited
state: Illinois
city: La Grange
country: United States
facility: AMITA Health Adventist Medical Center
state: Illinois
city: Elkhart
country: United States
facility: Elkhart Clinic
state: Indiana
city: Elkhart
country: United States
facility: Michiana Hematology Oncology PC-Elkhart
state: Indiana
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Kokomo
country: United States
facility: Community Howard Regional Health
state: Indiana
city: La Porte
country: United States
facility: IU Health La Porte Hospital
state: Indiana
city: Mishawaka
country: United States
facility: Michiana Hematology Oncology PC-Mishawaka
state: Indiana
city: Mishawaka
country: United States
facility: Saint Joseph Regional Medical Center-Mishawaka
state: Indiana
city: Plymouth
country: United States
facility: Michiana Hematology Oncology PC-Plymouth
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: South Bend
country: United States
facility: Michiana Hematology Oncology PC-South Bend
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Westville
country: United States
facility: Michiana Hematology Oncology PC-Westville
state: Indiana
city: Bettendorf
country: United States
facility: University of Iowa Healthcare Cancer Services Quad Cities
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Iowa City
country: United States
facility: Iowa City VA Healthcare System
state: Iowa
city: Augusta
country: United States
facility: Harold Alfond Center for Cancer Care
state: Maine
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Elkton
country: United States
facility: Union Hospital of Cecil County
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Milford
country: United States
facility: Dana-Farber/Brigham and Women's Cancer Center at Milford Regional
state: Massachusetts
city: Newton
country: United States
facility: Newton-Wellesley Hospital
state: Massachusetts
city: Niles
country: United States
facility: Lakeland Community Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: Marie Yeager Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota/Masonic Cancer Center
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri - Ellis Fischel
state: Missouri
city: Jefferson City
country: United States
facility: Capital Region Medical Center-Goldschmidt Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Center for Cancer Care and Research
state: Missouri
city: Saint Louis
country: United States
facility: Comprehensive Cancer Care PC
state: Missouri
city: Grand Island
country: United States
facility: CHI Health Saint Francis
state: Nebraska
city: Lincoln
country: United States
facility: Nebraska Cancer Research Center
state: Nebraska
city: North Platte
country: United States
facility: Great Plains Regional Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Omaha
country: United States
facility: Alegent Health Immanuel Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Alegent Health Bergan Mercy Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Creighton University Medical Center
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation CCOP
state: Nevada
city: Exeter
country: United States
facility: Exeter Hospital
state: New Hampshire
city: Laconia
country: United States
facility: LRGHealthcare-Lakes Region General Hospital
state: New Hampshire
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: East Syracuse
country: United States
facility: Hematology Oncology Associates of Central New York-East Syracuse
state: New York
city: Glens Falls
country: United States
facility: Glens Falls Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health/Center for Advanced Medicine
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Syracuse Veterans Administration Medical Center
state: New York
city: Asheboro
country: United States
facility: Randolph Hospital
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital
state: North Carolina
city: Greensboro
country: United States
facility: Cone Health Cancer Center
state: North Carolina
city: Kinston
country: United States
facility: Kinston Medical Specialists PA
state: North Carolina
city: Reidsville
country: United States
facility: Annie Penn Memorial Hospital
state: North Carolina
city: Statesville
country: United States
facility: Iredell Memorial Hospital
state: North Carolina
city: Washington
country: United States
facility: Marion L Shepard Cancer Center at Vidant Beaufort Hospital
state: North Carolina
city: Wilmington
country: United States
facility: New Hanover Regional Medical Center/Zimmer Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Pawtucket
country: United States
facility: Memorial Hospital of Rhode Island
state: Rhode Island
city: Easley
country: United States
facility: Greenville Health System Cancer Institute-Easley
state: South Carolina
city: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
city: Greenville
country: United States
facility: Saint Francis Hospital
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Andrews
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Butternut
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Faris
state: South Carolina
city: Greenville
country: United States
facility: Greenville Memorial Hospital
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Eastside
state: South Carolina
city: Greenwood
country: United States
facility: Self Regional Healthcare
state: South Carolina
city: Greer
country: United States
facility: Greenville Health System Cancer Institute-Greer
state: South Carolina
city: Seneca
country: United States
facility: Greenville Health System Cancer Institute-Seneca
state: South Carolina
city: Spartanburg
country: United States
facility: Greenville Health System Cancer Institute-Spartanburg
state: South Carolina
city: Berlin
country: United States
facility: Central Vermont Medical Center/National Life Cancer Treatment
state: Vermont
city: Burlington
country: United States
facility: University of Vermont College of Medicine
state: Vermont
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Martinsville
country: United States
facility: Memorial Hospital Of Martinsville
state: Virginia
city: Huntington
country: United States
facility: Saint Mary's Medical Center
state: West Virginia
Study officials:
affiliation: Alliance for Clinical Trials in Oncology
name: Rebecca Heist
role: PRINCIPAL_INVESTIGATOR
References: