ZD6474 in Treating Patients With Small Cell Lung Cancer

August 23, 2016 updated by: Genzyme, a Sanofi Company

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • 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

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre - Calgary
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute at University of Alberta
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 5L3
        • British Columbia Cancer Agency - Centre for the Southern Interior
      • Surrey, British Columbia, Canada, V3V 1Z2
        • Fraser/Valley Cancer Centre at British Columbia Cancer Agency
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • British Columbia Cancer Agency - Vancouver Cancer Centre
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6ZB
        • Moncton Hospital
      • Saint John, New Brunswick, Canada, E2L 4L2
        • Saint John Regional Hospital
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Margaret and Charles Juravinski Cancer Centre
      • Kingston, Ontario, Canada, K7L 5P9
        • Cancer Centre of Southeastern Ontario at Kingston General Hospital
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Hospital Regional Cancer Centre - General Campus
      • St. Catharines, Ontario, Canada, L2R 5K3
        • St. Catharines General Hospital at Niagara Health System
      • Thunder Bay, Ontario, Canada, P7B 6V4
        • Northwestern Ontario Regional Cancer Care at Thunder Bay Regional Health Sciences Centre
      • Toronto, Ontario, Canada, M4C 3E7
        • Toronto East General Hospital
      • Toronto, Ontario, Canada, M5G 1X5
        • Mount Sinai Hospital - Toronto
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre
      • Windsor, Ontario, Canada, N8W 2X3
        • Windsor Regional Cancer Centre at Windsor Regional Hospital
    • Quebec
      • Montreal, Quebec, Canada, H2W 1S6
        • McGill Cancer Centre at McGill University
      • Montreal, Quebec, Canada, H2L 4M1
        • Hopital Notre- Dame du CHUM
      • Ste-Foy, Quebec, Canada, G1V 4G5
        • L'Hopital Laval
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Saskatoon Cancer Centre at the University of Saskatchewan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 120 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • Over 16

Performance status

  • ECOG 0-2

Life expectancy

  • At least 12 weeks

Hematopoietic

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

Hepatic

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

Renal

  • Creatinine less than 1.5 times ULN
  • Calcium normal

Cardiovascular

  • 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

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

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

Chemotherapy

  • See Disease Characteristics
  • Recovered from prior chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • See Disease Characteristics
  • Recovered from prior radiotherapy

  • No concurrent anticancer radiotherapy

    • Concurrent low-dose, nonmyelosuppressive palliative radiotherapy allowed

Surgery

  • More than 2 weeks since prior major surgery

Other

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Progression-free survival

Secondary Outcome Measures

Outcome Measure
Pharmacokinetics
Response rates
Overall Survival
Toxicity and safety
Quality of life (QOL) as measured by EORTC QLQ-C30 and QLQ-LC13

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genzyme, a Sanofi Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2003

Primary Completion (Actual)

December 1, 2006

Study Completion (Actual)

December 1, 2006

Study Registration Dates

First Submitted

August 6, 2003

First Submitted That Met QC Criteria

August 6, 2003

First Posted (Estimate)

August 7, 2003

Study Record Updates

Last Update Posted (Estimate)

August 24, 2016

Last Update Submitted That Met QC Criteria

August 23, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D4200C00005
  • CAN-NCIC-BR20
  • ZENECA-6474IL/0005
  • CDR0000315518 (Other Identifier: Ct.gov temporary)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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