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ZD6474 in Treating Patients With Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00066313
Recruitment Status : Completed
First Posted : August 7, 2003
Last Update Posted : August 24, 2016
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Tracking Information
First Submitted Date  ICMJE August 6, 2003
First Posted Date  ICMJE August 7, 2003
Last Update Posted Date August 24, 2016
Study Start Date  ICMJE May 2003
Actual Primary Completion Date December 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2007)
Progression-free survival
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2007)
  • Overall Survival
  • Response rates
  • Toxicity and safety
  • Pharmacokinetics
  • Quality of life (QOL) as measured by EORTC QLQ-C30 and QLQ-LC13
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE ZD6474 in Treating Patients With Small Cell Lung Cancer
Official Title  ICMJE A Phase II Study Of ZD6474 Or Placebo In Small Cell Lung Cancer Patients Who Have Complete Or Partial Response To Induction Chemotherapy +/- Radiation Therapy
Brief Summary

RATIONALE: ZD6474 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. ZD6474 may also stop the growth of small cell lung cancer by blocking blood flow to the tumor.

PURPOSE: This randomized phase II trial is studying how well ZD6474 works compared to placebo in treating patients with small cell lung cancer that has responded to previous chemotherapy with or without radiation therapy.

Detailed Description


  • Compare the progression-free survival of patients with previously treated small cell lung cancer (SCLC) treated with ZD6474 vs placebo.
  • Compare the response rate of patients treated with these regimens (only patients who had measurable disease outside a prior radiation field at study entry).
  • Compare the toxicity and tolerability of these regimens in these patients.
  • Compare the pharmacokinetics of these regimens in these patients.
  • Correlate outcome and response with vascular endothelial growth factor expression and microvessel density in patients treated with these regimens.
  • Compare the quality of life of patients treated with these regimens.
  • Provide a comprehensive tumor, plasma, and urine bank linked to a clinical database for further study of molecular markers in SCLC.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center, timing of prior radiotherapy (early [before day 1, course 4 of chemotherapy] vs late vs no prior radiotherapy), stage of disease at diagnosis (limited vs extensive), and response at study entry (complete vs partial). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral ZD6474 daily.
  • Arm II: Patients receive oral placebo daily. In both arms, courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 4 weeks while on therapy, and then every 8 weeks until disease progression.

Patients are followed every 8 weeks until disease progression and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Masking: Double
Primary Purpose: Treatment
Condition  ICMJE Lung Cancer
Intervention  ICMJE
  • Drug: vandetanib
  • Procedure: adjuvant therapy
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE Not Provided
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE December 2006
Actual Primary Completion Date December 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE


  • Histologically or cytologically confirmed small cell carcinoma of the lung

    • Small cell and variant histology allowed
    • No mixed tumors (small and large cell)
    • No neuroendocrine tumors of the lung
  • Must have received at least 4 courses of first-line combination chemotherapy as part of an induction regimen

    • No prior change in regimen due to disease progression
  • Must have achieved a radiologically confirmed (i.e., CT scan, chest x-ray, or bone scan) complete response (CR) or partial response (PR) after prior chemotherapy with or without radiotherapy AND meets 1 of the following criteria:

    • No more than 28 days since prior chemotherapy
    • At least 7 and no more than 14 days since prior radiotherapy if administered after completion of prior chemotherapy*
  • No CNS metastases

    • Asymptomatic patients with CNS metastases who received prior therapeutic cranial irradiation and are on stable, decreasing, or no steroids are eligible
    • No symptomatic lesions or evidence of necrosis or bleeding NOTE: *Randomization may take place up to 21 days after prior radiotherapy in the instance of severe esophagitis that precludes administration of oral medications



  • Over 16

Performance status

  • ECOG 0-2

Life expectancy

  • At least 12 weeks


  • Absolute granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • No history of bleeding diathesis


  • Bilirubin less than 1.5 times upper limit of normal (ULN)
  • ALT less than 2.5 times ULN


  • Creatinine less than 1.5 times ULN
  • Calcium normal


  • No prior ventricular arrhythmia that was symptomatic or required treatment (CTC grade 3), including any of the following:

    • Multifocal premature ventricular contractions
    • Bigeminy
    • Trigeminy
    • Ventricular tachycardia
  • No prior QT prolongation with any medication
  • No congenital long QT syndrome
  • No QT and QTc (with Bazett's correction) that is unmeasurable or is 460 msec or higher on screening ECG
  • No significant cardiac event, including symptomatic heart failure or angina, within the past 3 months or any cardiac disease that increases the risk for ventricular arrhythmia
  • No ongoing chronic atrial fibrillation
  • LVEF at least 45% by MUGA for patients with significant cardiac history (myocardial infarction, severe hypertension, or arrhythmia) OR who received prior doxorubicin greater than 450 mg/m^2


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Potassium normal
  • Magnesium normal
  • No serious active infection
  • No recent major bleeding
  • No other concurrent serious underlying medical condition that would preclude study participation
  • Willing and able to complete quality of life questionnaires in English or French


Biologic therapy

  • No prior signal transduction inhibitors
  • No prior angiogenesis inhibitors
  • No concurrent anticancer biologic therapy or immunotherapy


  • See Disease Characteristics
  • Recovered from prior chemotherapy

Endocrine therapy

  • Not specified


  • See Disease Characteristics
  • Recovered from prior radiotherapy
  • No concurrent anticancer radiotherapy

    • Concurrent low-dose, nonmyelosuppressive palliative radiotherapy allowed


  • More than 2 weeks since prior major surgery


  • More than 4 weeks since prior investigational drugs
  • No prior epidermal growth factor receptor inhibitors
  • No prior vascular endothelial growth factor receptor inhibitors
  • No concurrent CYP3A4 inhibitors or inducers, including any of the following:

    • Verapamil
    • Rifampin
    • Phenytoin
    • Carbamazepine
    • Barbiturates
    • Hypericum perforatum (St. John's wort)
  • No concurrent medication that affects QT/QTc and/or induces torsades de pointes
  • No other concurrent anticancer cytotoxic therapy
  • No other concurrent investigational drugs during and for 30 days after study participation
  • No concurrent oral bisphosphonates (e.g., clodronate)

    • Concurrent IV bisphosphonates allowed
  • No concurrent 5HT_3 antagonists
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 120 Years   (Child, 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 Canada
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00066313
Other Study ID Numbers  ICMJE D4200C00005
CDR0000315518 ( Other Identifier: temporary )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi ( Genzyme, a Sanofi Company )
Study Sponsor  ICMJE Genzyme, a Sanofi Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date August 2016

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