Cisplatin or Carboplatin, and Etoposide With or Without Sunitinib Malate in Treating Patients With Extensive-Stage Small Cell Lung Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Extensive Stage Lung Small Cell Carcinoma; Recurrent Lung Small Cell Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Carboplatin; Drug: Etoposide; Drug: Cisplatin; Other: Placebo Administration; Drug: Sunitinib Malate

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.

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Arroyo Grande, California, United States, 93420
      • PCR Oncology
    • Arroyo Grande, California, United States, 93420
      • Arroyo Grande Community
    • Castro Valley, California, United States, 94546
      • East Bay Radiation Oncology Center
    • Castro Valley, California, United States, 94546
      • Valley Medical Oncology Consultants-Castro Valley
    • Emeryville, California, United States, 94608
      • Bay Area Breast Surgeons Inc
    • Fremont, California, United States, 94538
      • Valley Medical Oncology Consultants-Fremont
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Mountain View, California, United States, 94040
      • El Camino Hospital
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94609
      • Hematology and Oncology Associates-Oakland
    • Oakland, California, United States, 94602
      • Highland General Hospital
    • Oakland, California, United States, 94609
      • Tom K Lee Inc
    • Oakland, California, United States, 94609
      • Bay Area Tumor Institute
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • San Pablo, California, United States, 94806
      • Doctors Medical Center- JC Robinson Regional Cancer Center
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Gainesville, Florida, United States, 32605
      • Florida Cancer Specialists-Gainesville Cancer Center
    • Jupiter, Florida, United States, 33458
      • Jupiter Medical Center
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
  • Georgia
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Bloomington, Illinois, United States, 61701
      • Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Canton, Illinois, United States, 61520
      • Graham Hospital Association
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Decatur, Illinois, United States, 62526
      • Heartland Cancer Research NCORP
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Eureka, Illinois, United States, 61530
      • Eureka Hospital
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Havana, Illinois, United States, 62644
      • Illinois CancerCare-Havana
    • Hopedale, Illinois, United States, 61747
      • Hopedale Medical Complex - Hospital
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Kewanee, Illinois, United States, 61443
      • Kewanee Hospital
    • La Grange, Illinois, United States, 60525
      • AMITA Health Adventist Medical Center
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Monmouth, Illinois, United States, 61462
      • Illinois CancerCare-Monmouth
    • Monmouth, Illinois, United States, 61462
      • Holy Family Medical Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center Foundation
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Illinois CancerCare-Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Ottawa, Illinois, United States, 61350
      • Ottawa Regional Hospital and Healthcare Center
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Pekin, Illinois, United States, 61554
      • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
    • Pekin, Illinois, United States, 61554
      • Pekin Hospital
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Peru, Illinois, United States, 61354
      • Illinois Valley Hospital
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Rockford, Illinois, United States, 61108
      • OSF Saint Anthony Medical Center
    • Spring Valley, Illinois, United States, 61362
      • Saint Margaret's Hospital
    • Spring Valley, Illinois, United States, 61362
      • Illinois CancerCare-Spring Valley
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Elkhart, Indiana, United States, 46514
      • Michiana Hematology Oncology PC-Elkhart
    • Elkhart, Indiana, United States, 46514-2098
      • Elkhart Clinic
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology Inc-Parkview
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Mishawaka, Indiana, United States, 46545
      • Michiana Hematology Oncology PC-Mishawaka
    • Mishawaka, Indiana, United States, 46545
      • Saint Joseph Regional Medical Center-Mishawaka
    • Plymouth, Indiana, United States, 46563
      • Michiana Hematology Oncology PC-Plymouth
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • Michiana Hematology Oncology PC-South Bend
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium
    • South Bend, Indiana, United States, 46617
      • South Bend Clinic
    • Westville, Indiana, United States, 46391
      • Michiana Hematology Oncology PC-Westville
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Elkton, Maryland, United States, 21921
      • Union Hospital of Cecil County
    • Salisbury, Maryland, United States, 21801
      • Peninsula Regional Medical Center
  • Massachusetts
    • Gloucester, Massachusetts, United States, 01930
      • Addison Gilbert Hospital
  • Michigan
    • Niles, Michigan, United States, 49120
      • Lakeland Hospital Niles
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center Saint Joseph
    • Saint Joseph, Michigan, United States, 49085
      • Marie Yeager Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota/Masonic Cancer Center
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Medical Center
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • CHI Health Saint Francis
    • Lincoln, Nebraska, United States, 68510
      • Nebraska Cancer Research Center
    • North Platte, Nebraska, United States, 69101
      • Great Plains Health Callahan Cancer Center
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegent Health Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68122
      • Alegent Health Immanuel Medical Center
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
    • Omaha, Nebraska, United States, 68106
      • Missouri Valley Cancer Consortium
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • New Hampshire Oncology Hematology PA-Concord
    • Hooksett, New Hampshire, United States, 03106
      • New Hampshire Oncology Hematology PA-Hooksett
    • Laconia, New Hampshire, United States, 03246
      • LRGHealthcare-Lakes Region General Hospital
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of Central New York-East Syracuse
    • Glens Falls, New York, United States, 12801
      • Glens Falls Hospital
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10035
      • Ralph Lauren Center for Cancer Care and Prevention
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth of the Carolinas-Moore Regional Hospital
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
    • Providence, Rhode Island, United States, 02906
      • Miriam Hospital
  • South Carolina
    • Beaufort, South Carolina, United States, 29902
      • Beaufort Memorial Hospital
    • Florence, South Carolina, United States, 29506
      • McLeod Regional Medical Center
  • Vermont
    • Berlin, Vermont, United States, 05602
      • Central Vermont Medical Center/National Life Cancer Treatment
    • Burlington, Vermont, United States, 05405
      • University of Vermont and State Agricultural College
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (Combination Chemotherapy + Sunitinib Maintenance); Participants will receive the following combination chemotherapy for 4-6 cycles (21 days): Cisplatin 80 mg/m^2 by IV over 1 hour on day 1 every cycle OR Carboplatin AUC = 5* by IV Etoposide 100 mg/m^2 by IV over 1 hour on days 1, 2, and 3 every cycle Maintenance: Following 4-6 cycles of combination chemotherapy, start sunitinib at 150 mg on day 1, then 37.5 daily until disease progression.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Peyrone''s Chloride; Peyrone''s Salt; Drug: Sunitinib Malate; Given PO; Other Names: Sutent; SU011248; SU11248; sunitinib
Active Comparator: Arm II (Combination Chemotherapy + Placebo Maintenance); Participants will receive the following combination chemotherapy for 4-6 cycles (21 days): Cisplatin 80 mg/m^2 by IV over 1 hour on day 1 every cycle OR Carboplatin AUC = 5* by IV Etoposide 100 mg/m2 by IV over 1 hour on days 1, 2, and 3 every cycle Maintenance: Following 4-6 cycles of combination chemotherapy, start placebo at 150 mg on day 1, then 37.5 daily until disease progression.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Peyrone''s Chloride; Peyrone''s Salt; Other: Placebo Administration; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated of Sunitinib Combined With Cisplatin and Etoposide (Phase I)	The maximum tolerated dose is defined at the highest sunitinib dose at which less than one third of participants develop a dose limiting toxicity (DLT). A DLT is defined as: delay of beginning cycle 2 of chemotherapy by > 7 days due to neutropenia, grade 4 hematologic toxicity lasting greater than 1 week (chemotherapy alone would be expected to cause significant grade 4 hematologic toxicity) or grade 3 or 4 nonhematologic toxicity (excluding grade 3 or 4 fatigue if the patient is found to be hypothyroid and responds to fatigue < grade 3 with thyroid replacement therapy).	21 days
Progression-free Survival (Phase II)	Progression free survival (PFS) was defined as the time from maintenance randomization to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival (OS) was defined as the time from randomization to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.	Up to 3 years
Number of Participants With Overall Tumor Response	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; Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria. Overall tumor response is the total number of CR and PRs.	Up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Plasma Levels of VEGF Prior to, During Single-agent, and Following Treatment With Sunitinib Malate	The frequency of tumor response by the optimally dichotomized VEGF levels will be tabulated and their association will be tested by Fisher's exact test as well as the maximally selected rank test. The association of the VEGF levels as continuous predictor with tumor response will be tested by Wilcoxon rank sum test. Further assessments of the association of the VEGF levels as> continuous or binary variables and the tumor response will be implemented in a logistic regression while adjusting for other covariates such as performance status, weight loss and age	Baseline to within 7 days of sunitinib/placebo therapy discontinuation
Change in Plasma Levels of PDGF	Correlated with clinical outcome (response and survival).	Baseline to within 7 days of sunitinib/placebo therapy discontinuation

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Neal E Ready, Alliance for Clinical Trials in Oncology

Publications and helpful links

General Publications

• 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.

Helpful Links

• Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2007
• Primary Completion (Actual): June 30, 2013
• Study Completion (Actual): August 20, 2015

Study Registration Dates

• First Submitted: March 27, 2007
• First Submitted That Met QC Criteria: March 27, 2007
• First Posted (Estimate): March 28, 2007

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: March 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma; Small Cell Lung Carcinoma; Carcinoma, Small Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dermatologic Agents; Protein Kinase Inhibitors; Keratolytic Agents; Carboplatin; Etoposide; Etoposide phosphate; Cisplatin; Sunitinib; Podophyllotoxin
• Other Study ID Numbers: NCI-2009-00465 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180821 (U.S. NIH Grant/Contract); U10CA031946 (U.S. NIH Grant/Contract); CDR0000538229; CALGB 30504 (Other Identifier: Alliance for Clinical Trials in Oncology); CALGB-30504 (Other Identifier: CTEP)