Clinical trial NCT00453154: Cisplatin or Carboplatin, and Etoposide With or Without Sunitinib Malate in Treating Patients With Extensive-Stage Small Cell Lung Cancer
Official title: Combination Chemotherapy With or Without Maintenance Sunitinib Malate (NSC 736511) for Untreated Extensive Stage Small Cell Lung Cancer: A Phase IB/Randomized Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Extensive Stage Lung Small Cell Carcinoma
Recurrent Lung Small Cell Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-03-28
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This partially randomized phase I/II trial studies the side effects and best dose of sunitinib malate and to see how well it works when given together with cisplatin or carboplatin and etoposide in treating patients with extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as cisplatin, carboplatin, and etoposide, 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 cisplatin or carboplatin and etoposide are more effective when given with or without sunitinib malate in treating small cell lung cancer.

Detailed description: PRIMARY OBJECTIVES:

I. To determine the phase II dose for sunitinib (sunitinib malate) combined with cisplatin and etoposide. (Phase IB) II. To compare the progression-free survival of patients with extensive stage small cell lung cancer treated with cisplatin or carboplatin and etoposide followed by maintenance sunitinib to patients receiving the same chemotherapy followed by placebo. (Phase II)

SECONDARY OBJECTIVES:

I. To assess the single agent response rate for sunitinib given as monotherapy after chemotherapy. (Phase II) II. To assess the overall survival of patients treated with cisplatin or carboplatin and etoposide followed by sunitinib. (Phase II) III. To evaluate the toxicity and tolerability of maintenance sunitinib after cisplatin or carboplatin and etoposide. (Phase II) IV. To determine the association between vascular endothelial growth factor (VEGF) plasma levels and tumor response. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of sunitinib malate followed by a randomized phase II study.

PHASE I (close to accrual 5/17/08):

COMBINATION THERAPY: Patients receive cisplatin or carboplatin intravenously (IV) on day 1, etoposide IV on days 1-3, and sunitinib malate orally (PO) once daily (QD) on days 1-14. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive sunitinib malate PO alone QD. Treatment continues in the absence of disease progression or unacceptable toxicity.

PHASE II:

COMBINATION THERAPY: Patients receive cisplatin or carboplatin and etoposide as in Phase I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Beginning 3-8 weeks after completion of combination chemotherapy or \>= 4 courses of combination therapy, patients with a responding or stable disease are randomized to 1 of 2 treatment arms. All patients must be euthyroid before starting on maintenance therapy.

ARM I: Patients receive sunitinib malate PO QD. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO QD. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm I.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.

Eligibility criteria: Inclusion Criteria:

* All patients must have histologically or cytologically documented small cell lung cancer

  * Eligible disease stages: the extensive disease classification for this protocol includes all patients with disease sites not defined as limited stage; limited stage disease category includes patients with disease restricted to one hemithorax with regional lymph node metastases, including hilar, ipsilateral and contralateral mediastinal, and/or ipsilateral supraclavicular nodes; extensive stage patients are defined as those patients with extrathoracic metastatic, malignant pleural effusion, bilateral or contralateral supraclavicular adenopathy or contralateral hilar adenopathy
* All patients must have measurable disease:

  * Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
  * Lesions that are considered non-measurable, which would make the patient not eligible, 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
* No prior chemotherapy for small cell lung cancer (SCLC)
* Radiation therapy must have been completed at least one week before initiation of protocol therapy
* Common Toxicity Criteria (CTC) performance status:

  * Phase IB: 0-1
  * Phase II: 0-2
* No "currently active" second malignancy other than non-melanoma skin cancers
* No history of brain metastases, spinal cord compression, or carcinomatous meningitis
* No ongoing cardiac dysrhythmias, atrial fibrillation, or QTc interval \>= 500 msec; the use of agents with proarrhythmic potential (e.g., quinidine, procainamide, disopyramide, sotalol, probucol, pedridel, haloperidol, risperidone, indapamide, flecainide) is not recommended while on protocol therapy
* Patients with class I New York Heart Association (NYHA) are eligible; patients with a history of class II NYHA are eligible, provided they meet 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 class III or IV NYHA heart failure within 12 months prior to registration are not eligible
* Additionally, no myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft or stenting, cerebrovascular accident including transient ischemic attack, or pulmonary embolism 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 doses of coumarin-derivative anticoagulants such as warfarin are excluded, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis; Note: Low molecular weight heparin is permitted provided the patient's prothrombin time (PT) international normalized ratio (INR) is =\< 1.5
* No evidence of hemoptysis within 4 weeks prior to starting study treatment; 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
* None of the following within 28 days of 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 there use is discouraged
* Non-pregnant and non-nursing
* Granulocytes \>= 1,500/ul
* Platelets \>= 100,000/ul
* Creatinine clearance \>= 70 ml/min
* Total bilirubin =\< 1.5 mg/dl
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN) (patients w/ liver metastases may have AST/ALT =\< 5 x ULN)
* Partial thromboplastin time (PTT) =\< 1.5 x ULN

Primary outcomes:
measure: Maximum Tolerated of Sunitinib Combined With Cisplatin and Etoposide (Phase I)
timeFrame: 21 days
measure: Progression-free Survival (Phase II)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to 3 years
measure: Number of Participants With Overall Tumor Response
timeFrame: Up to 3 years
Other outcomes:
measure: Change in Plasma Levels of VEGF Prior to, During Single-agent, and Following Treatment With Sunitinib Malate
timeFrame: Baseline to within 7 days of sunitinib/placebo therapy discontinuation
measure: Change in Plasma Levels of PDGF
timeFrame: Baseline to within 7 days of sunitinib/placebo therapy discontinuation
Locations:
city: Arroyo Grande
country: United States
facility: Arroyo Grande Community
state: California
city: Arroyo Grande
country: United States
facility: PCR Oncology
state: California
city: Castro Valley
country: United States
facility: East Bay Radiation Oncology 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: Fremont
country: United States
facility: Valley Medical Oncology Consultants-Fremont
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: San Francisco
country: United States
facility: UCSF Medical Center-Mount Zion
state: California
city: San Pablo
country: United States
facility: Doctors Medical Center- JC Robinson Regional Cancer Center
state: California
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: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Gainesville
country: United States
facility: Florida Cancer Specialists-Gainesville Cancer Center
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: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Bloomington
country: United States
facility: Saint Joseph Medical Center
state: Illinois
city: Bloomington
country: United States
facility: Illinois CancerCare-Bloomington
state: Illinois
city: Canton
country: United States
facility: Graham Hospital Association
state: Illinois
city: Canton
country: United States
facility: Illinois CancerCare-Canton
state: Illinois
city: Carthage
country: United States
facility: Illinois CancerCare-Carthage
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Decatur
country: United States
facility: Heartland Cancer Research NCORP
state: Illinois
city: Eureka
country: United States
facility: Eureka Hospital
state: Illinois
city: Eureka
country: United States
facility: Illinois CancerCare-Eureka
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare-Galesburg
state: Illinois
city: Havana
country: United States
facility: Illinois CancerCare-Havana
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex - Hospital
state: Illinois
city: Kewanee
country: United States
facility: Illinois CancerCare-Kewanee Clinic
state: Illinois
city: Kewanee
country: United States
facility: Kewanee Hospital
state: Illinois
city: La Grange
country: United States
facility: AMITA Health Adventist Medical Center
state: Illinois
city: Macomb
country: United States
facility: Illinois CancerCare-Macomb
state: Illinois
city: Macomb
country: United States
facility: Mcdonough District Hospital
state: Illinois
city: Monmouth
country: United States
facility: Holy Family Medical Center
state: Illinois
city: Monmouth
country: United States
facility: Illinois CancerCare-Monmouth
state: Illinois
city: Normal
country: United States
facility: Bromenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center Foundation
state: Illinois
city: Normal
country: United States
facility: Illinois CancerCare-Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Illinois CancerCare-Ottawa Clinic
state: Illinois
city: Ottawa
country: United States
facility: Ottawa Regional Hospital and Healthcare Center
state: Illinois
city: Pekin
country: United States
facility: Illinois CancerCare-Pekin
state: Illinois
city: Pekin
country: United States
facility: OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
state: Illinois
city: Pekin
country: United States
facility: Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois CancerCare-Peru
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Hospital
state: Illinois
city: Princeton
country: United States
facility: Illinois CancerCare-Princeton
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Rockford
country: United States
facility: OSF Saint Anthony Medical Center
state: Illinois
city: Spring Valley
country: United States
facility: Illinois CancerCare-Spring Valley
state: Illinois
city: Spring Valley
country: United States
facility: Saint Margaret's Hospital
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: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology Inc-Parkview
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: South Bend Clinic
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: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Elkton
country: United States
facility: Union Hospital of Cecil County
state: Maryland
city: Salisbury
country: United States
facility: Peninsula Regional Medical Center
state: Maryland
city: Gloucester
country: United States
facility: Addison Gilbert Hospital
state: Massachusetts
city: Niles
country: United States
facility: Lakeland Hospital Niles
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Medical Center Saint Joseph
state: Michigan
city: Saint Joseph
country: United States
facility: Marie Yeager Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis VA Medical Center
state: Minnesota
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: Saint Louis
country: United States
facility: Washington University School of Medicine
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 Health Callahan Cancer Center
state: Nebraska
city: Omaha
country: United States
facility: Missouri Valley Cancer Consortium
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: Concord
country: United States
facility: New Hampshire Oncology Hematology PA-Concord
state: New Hampshire
city: Hooksett
country: United States
facility: New Hampshire Oncology Hematology PA-Hooksett
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: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
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: New York
country: United States
facility: Ralph Lauren Center for Cancer Care and Prevention
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital
state: North Carolina
city: Hendersonville
country: United States
facility: Margaret R Pardee Memorial Hospital
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth of the Carolinas-Moore Regional Hospital
state: North Carolina
city: Statesville
country: United States
facility: Iredell Memorial Hospital
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: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: Miriam Hospital
state: Rhode Island
city: Beaufort
country: United States
facility: Beaufort Memorial Hospital
state: South Carolina
city: Florence
country: United States
facility: McLeod Regional Medical Center
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 and State Agricultural College
state: Vermont
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
Study officials:
affiliation: Alliance for Clinical Trials in Oncology
name: Neal E Ready
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy With or Without Maintenance Sunitinib for Untreated Extensive-Stage Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase II Study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. doi: 10.1200/JCO.2014.57.3105. Epub 2015 Mar 2.