Phase II Metastatic ER+/PgR+ Nolvadex +/- Iressa Study

October 2, 2015 updated by: AstraZeneca

A Phase II Randomised, Double-Blind, Stratified, Multi-Centre Trial Comparing the Nolvadex 20 Mg And Placebo Combination To The Nolvadex 20 Mg and ZD1839 (IRESSA™) 250 MG Combination In Patients With Metastatic Breast Cancer And Estrogen Receptor (ER) and/or Progesterone (PR) Positive Tumours

This study is being carried out to see if ZD1839 is effective in treating metastatic breast cancer in combination with Nolvadex, and if so, how it compares with Nolvadex alone.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

317

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

  • Argentina
      • Bahía Blanca, Argentina
        • Research Site
      • Ciudad de Buenos Aires, Argentina
        • Research Site
      • Córdoba, Argentina
        • Research Site
      • El Palomar, Argentina
        • Research Site
      • Resistencia, Argentina
        • Research Site
      • Rosario, Argentina
        • Research Site
      • San Miguel de Tucuman, Argentina
        • Research Site
      • Santa Fe, Argentina
        • Research Site
      • Vicente Lopez, Argentina
        • Research Site
  • Australia
      • Bentleigh East, Australia
        • Research Site
      • Newcastle, Australia
        • Research Site
      • Randwick, Australia
        • Research Site
      • Westmead, Australia
        • Research Site
      • Wodonga, Australia
        • Research Site
  • Belgium
      • Brussels, Belgium
        • Research Site
      • Leuven, Belgium
        • Research Site
      • Wilrijk, Belgium
        • Research Site
  • Brazil
      • Belo Horizonte, Brazil
        • Research Site
      • Curitiba, Brazil
        • Research Site
      • Porto Alegre, Brazil
        • Research Site
      • Sao Paulo, Brazil
        • Research Site
      • São Paulo, Brazil
        • Research Site
  • Canada
      • Quebec, Canada
        • Research Site
    • Alberta
      • Calgary, Alberta, Canada
        • Research Site
      • Edmonton, Alberta, Canada
        • Research Site
    • New Brunswick
      • Saint John, New Brunswick, Canada
        • Research Site
    • Ontario
      • Ottawa, Ontario, Canada
        • Research Site
      • Toronto, Ontario, Canada
        • Research Site
    • Quebec
      • Montreal, Quebec, Canada
        • Research Site
  • Denmark
      • Herlev, Denmark
        • Research Site
  • France
      • Lyon Cedex 08, France
        • Research Site
      • Mougins, France
        • Research Site
      • Poitiers, France
        • Research Site
      • Rouen, France
        • Research Site
  • Germany
      • Frankfurt, Germany
        • Research Site
      • Jena, Germany
        • Research Site
      • Kiel, Germany
        • Research Site
      • München, Germany
        • Research Site
      • Trier, Germany
        • Research Site
  • South Africa
      • Durban, South Africa
        • Research Site
      • Johannesburg, South Africa
        • Research Site
      • Klerksdorp, South Africa
        • Research Site
      • Observatory, South Africa
        • Research Site
  • Spain
      • Barcelona, Spain
        • Research Site
      • Córdoba, Spain
        • Research Site
      • Madrid, Spain
        • Research Site
      • Majadahonda, Spain
        • Research Site
      • Zaragoza, Spain
        • Research Site
  • United Kingdom
      • Colchester, United Kingdom
        • Research Site
      • Dundee, United Kingdom
        • Research Site
      • Manchester, United Kingdom
        • Research Site
      • Nottingham, United Kingdom
        • Research Site
  • United States
    • California
      • Berkeley, California, United States
        • Research Site
      • Palm Springs, California, United States
        • Research Site
    • Missouri
      • St. Louis, Missouri, United States
        • Research Site
    • New York
      • New York, New York, United States
        • Research Site

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

18 years to 130 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Histologically confirmed metastatic adenocarcinoma of the breast (seeTNM staging Appendix I) that is ER and/or PR positive as determined in local laboratories at each investigator site (central verification of ER status will be performed after the patient starts treatment
  • A tissue block from either the metastatic or primary tumor site is required.
  • WHO performance status (PS) 0-2
  • Patients must not be pregnant or breast-feeding. A negative pregnancy test is required within 7 days prior to randomization if pre- or peri-menopausal. Postmenopausal patients are defined as:
  • natural menopause with last menses > 1 year ago,
  • radiation induced oophorectomy with last menses > 1 year ago,
  • chemotherapy induced menopause with 1 year interval since last menses, or
  • serum FSH and LH and plasma estradiol levels in the postmenopausal range for the institution.
  • bilateral oophorectomy

Exclusion Criteria:

  • Patients cannot be on hormone replacement therapy or received prior chemotherapy for metastatic disease.
  • Patients previously treated with a Tyrosine Kinase inhibitor or have evidence of an active interstitial lung disease are not eligible.
  • Treatment with LH-RH analog.
  • Laboratory values as follow Bilirubin >1.5 times upper limit of normal ULN, alanine amino transferase (ALT) or aspartate amino transferase (AST) >2.5 times the ULN if no demonstrable liver metastases, or >5 times the ULN in the presence of liver metastases
  • Bone marrow function: WBC <1500 mm3

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
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
ZD1839 + Nolvadex
Drug: Tamoxifen
Other Names:
  • Nolvadex
Drug: Gefitinib
Other Names:
  • Iressa
Other: 2
Nolvadex + placebo
Drug: Tamoxifen
Other Names:
  • Nolvadex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Strata 1: To compare the time to progression between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex)
Time Frame: Time to progression (progressive disease or death; equivalent to progression-free survival)
Time to progression (progressive disease or death; equivalent to progression-free survival)
Strata 2: To compare the clinical benefit rate between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex)
Time Frame: Overall clinical benefit rate: Complete Response, Partial Response or Stable Disease > 24weeks after each combination
Overall clinical benefit rate: Complete Response, Partial Response or Stable Disease > 24weeks after each combination

Secondary Outcome Measures

Outcome Measure
Time Frame
To compare the clinical benefit rate between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex) in Strata 1 and overall
Time Frame: Overall clinical benefit rate: Complete Response, Partial Response or Stable Disease >24 weeks after each combination. Objective tumour resp defined according to RECIST criteria
Overall clinical benefit rate: Complete Response, Partial Response or Stable Disease >24 weeks after each combination. Objective tumour resp defined according to RECIST criteria
To compare time to progression between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex) in Strata 2 and overall
Time Frame: Time to progression (progressive disease or death)
Time to progression (progressive disease or death)
To compare the objective response rate between ZD1839/Nolvadex and placebo/Nolvadex in each strata and overall
Time Frame: Objective tumour response (OR) defined according to RECIST criteria
Objective tumour response (OR) defined according to RECIST criteria
To estimate duration of response for the ZD1839/Nolvadex and placebo/Nolvadex treatments in each strata and overall
Time Frame: Duration of response (CR and PR)
Duration of response (CR and PR)
To compare overall survival between the ZD1839/Nolvadex and placebo/Nolvadex in each strata
Time Frame: Overall survival
Overall survival
To assess whether patients with high tumour levels of HER-2 and/or AIB1 demonstrate de novo resistance to Nolvadex therapy or have shorter TTP or response duration when compared with Nolvadex/ZD1839 treatment
Time Frame: Time to progression (progressive disease or death), duration of response (CR and PR)
Time to progression (progressive disease or death), duration of response (CR and PR)
To compare the objective response rate between the ZD1839/Nolvadex and placebo/Nolvadex treatment arms in the subset of all patients with ER+ tumours staining 2+/3+ for Her2neu by IHC
Time Frame: Objective tumour response (OR) defined according to RECIST criteria
Objective tumour response (OR) defined according to RECIST criteria
To compare the safety and tolerability of ZD1839/Nolvadex to placebo/Nolvadex
Time Frame: Safety (frequency and severity of adverse events)
Safety (frequency and severity of adverse events)
To determine steady-state plasma trough concentrations of tamoxifen in all patients and to compare between the ZD1839/Nolvadex and placebo/Nolvadex treatment arms
Time Frame: Tamoxifen (Cmin) steady-state plasma concentration
Tamoxifen (Cmin) steady-state plasma concentration
To determine steady-state plasma trough concentrations of ZD1839 and relate values to historical data
Time Frame: ZD1839 (Cmin) steady-state plasma concentration
ZD1839 (Cmin) steady-state plasma concentration
To relate steady-state plasma trough concentrations of ZD1839 to demographic, response, and safety variables
Time Frame: ZD1839 (Cmin) steady-state plasma concentration
ZD1839 (Cmin) steady-state plasma concentration
To assess the quality of life (QOL) and symptom relief based on the Functional Assessment of Cancer Therapy - Breast (FACT-B) on both treatment arms
Time Frame: FACT-B questionnaire, FBSI (FACT-B Symptom Index)
FACT-B questionnaire, FBSI (FACT-B Symptom Index)
To investigate subject hospital resource use and health status
Time Frame: Hospitalisations and EQ-5D
Hospitalisations and EQ-5D
Characterization of specific adverse events
Time Frame: Characterization of adverse events such as alopecia, rash and diarrhea
Characterization of adverse events such as alopecia, rash and diarrhea
To obtain tumour tissue for biologic studies in this patient population
Time Frame: ER receptor, ErbB-1 &2 (immunohistochemistry) and other biological markers including Her2/neu, AIB1
ER receptor, ErbB-1 &2 (immunohistochemistry) and other biological markers including Her2/neu, AIB1

Collaborators and Investigators

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

Sponsor

AstraZeneca

Investigators

  • Study Director: AstraZeneca Iressa Medical Science Director, MD, AstraZeneca

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.

Helpful Links

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

October 1, 2003

Primary Completion (Actual)

December 1, 2006

Study Completion (Actual)

June 1, 2015

Study Registration Dates

First Submitted

September 28, 2005

First Submitted That Met QC Criteria

September 28, 2005

First Posted (Estimate)

September 30, 2005

Study Record Updates

Last Update Posted (Estimate)

October 5, 2015

Last Update Submitted That Met QC Criteria

October 2, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1839IL/0225
  • D7917C00225

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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