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Trial record 1 of 1 for:    CALGB 30504
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Cisplatin or Carboplatin, and Etoposide With or Without Sunitinib Malate in Treating Patients With Extensive-Stage Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT00453154
Recruitment Status : Active, not recruiting
First Posted : March 28, 2007
Results First Posted : April 14, 2015
Last Update Posted : April 16, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE March 27, 2007
First Posted Date  ICMJE March 28, 2007
Results First Submitted Date  ICMJE March 24, 2015
Results First Posted Date  ICMJE April 14, 2015
Last Update Posted Date April 16, 2019
Actual Study Start Date  ICMJE March 15, 2007
Actual Primary Completion Date June 30, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2015)
  • Maximum Tolerated of Sunitinib Combined With Cisplatin and Etoposide (Phase I) [ Time Frame: 21 days ]
    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).
  • Progression-free Survival (Phase II) [ Time Frame: Up to 3 years ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 27, 2007)
  • Percentage of patients who live > 10 months (phase II)
  • Efficacy (phase II)
Change History Complete list of historical versions of study NCT00453154 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2015)
  • Overall Survival [ Time Frame: Up to 3 years ]
    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.
  • Number of Participants With Overall Tumor Response [ Time Frame: Up to 3 years ]
    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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: April 10, 2015)
  • Change in Plasma Levels of VEGF Prior to, During Single-agent, and Following Treatment With Sunitinib Malate [ Time Frame: Baseline to within 7 days of sunitinib/placebo therapy discontinuation ]
    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
  • Change in Plasma Levels of PDGF [ Time Frame: Baseline to within 7 days of sunitinib/placebo therapy discontinuation ]
    Correlated with clinical outcome (response and survival).
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cisplatin or Carboplatin, and Etoposide With or Without Sunitinib Malate in Treating Patients With Extensive-Stage Small Cell Lung Cancer
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Extensive Stage Lung Small Cell Carcinoma
  • Recurrent Lung Small Cell Carcinoma
Intervention  ICMJE
  • Drug: Carboplatin
    Given IV
    Other Names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Drug: Cisplatin
    Given IV
    Other Names:
    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum
    • Cis-dichloroammine Platinum (II)
    • Cis-platinous Diamine Dichloride
    • Cis-platinum
    • Cis-platinum II
    • Cis-platinum II Diamine Dichloride
    • Cismaplat
    • Cisplatina
    • Cisplatinum
    • Cisplatyl
    • Citoplatino
    • Citosin
    • Cysplatyna
    • DDP
    • Lederplatin
    • Metaplatin
    • Neoplatin
    • Peyrone's Chloride
    • Peyrone's Salt
    • Placis
    • Plastistil
    • Platamine
    • Platiblastin
    • Platiblastin-S
    • Platinex
    • Platinol
    • Platinol- AQ
    • Platinol-AQ
    • Platinol-AQ VHA Plus
    • Platinoxan
    • Platinum
    • Platinum Diamminodichloride
    • Platiran
    • Platistin
    • Platosin
  • Drug: Etoposide
    Given IV
    Other Names:
    • Demethyl Epipodophyllotoxin Ethylidine Glucoside
    • EPEG
    • Lastet
    • Toposar
    • Vepesid
    • VP 16-213
    • VP-16
    • VP-16-213
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Placebo
    Given PO
    Other Names:
    • placebo therapy
    • PLCB
    • sham therapy
  • Drug: Sunitinib Malate
    Given PO
    Other Names:
    • SU011248
    • SU11248
    • sunitinib
    • Sutent
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: Carboplatin
    • Drug: Cisplatin
    • Drug: Etoposide
    • Other: Laboratory Biomarker Analysis
    • Drug: Sunitinib Malate
  • 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.

    Interventions:
    • Drug: Carboplatin
    • Drug: Cisplatin
    • Drug: Etoposide
    • Other: Laboratory Biomarker Analysis
    • Other: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 30, 2014)
156
Original Enrollment  ICMJE
 (submitted: March 27, 2007)
107
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date June 30, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00453154
Other Study ID Numbers  ICMJE NCI-2009-00465
NCI-2009-00465 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000538229
CALGB 30504 ( Other Identifier: Alliance for Clinical Trials in Oncology )
CALGB-30504 ( Other Identifier: CTEP )
U10CA180821 ( U.S. NIH Grant/Contract )
U10CA031946 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Neal E Ready Alliance for Clinical Trials in Oncology
PRS Account National Cancer Institute (NCI)
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP