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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00229697




Registration number
NCT00229697
Ethics application status
Date submitted
28/09/2005
Date registered
30/09/2005
Date last updated
5/10/2015

Titles & IDs
Public title
Phase II Metastatic ER+/PgR+ Nolvadex +/- Iressa Study
Scientific title
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
Secondary ID [1] 0 0
D7917C00225
Secondary ID [2] 0 0
1839IL/0225
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Gefitinib
Treatment: Drugs - Tamoxifen

Experimental: 1 - ZD1839 + Nolvadex

Other: 2 - Nolvadex + placebo


Treatment: Drugs: Gefitinib


Treatment: Drugs: Tamoxifen
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Strata 1: To compare the time to progression between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex)
Timepoint [1] 0 0
Time to progression (progressive disease or death; equivalent to progression-free survival)
Primary outcome [2] 0 0
Strata 2: To compare the clinical benefit rate between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex)
Timepoint [2] 0 0
Overall clinical benefit rate: Complete Response, Partial Response or Stable Disease > 24weeks after each combination
Secondary outcome [1] 0 0
To compare the clinical benefit rate between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex) in Strata 1 and overall
Timepoint [1] 0 0
Overall clinical benefit rate: Complete Response, Partial Response or Stable Disease >24 weeks after each combination. Objective tumour resp defined according to RECIST criteria
Secondary outcome [2] 0 0
To compare time to progression between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex) in Strata 2 and overall
Timepoint [2] 0 0
Time to progression (progressive disease or death)
Secondary outcome [3] 0 0
To compare the objective response rate between ZD1839/Nolvadex and placebo/Nolvadex in each strata and overall
Timepoint [3] 0 0
Objective tumour response (OR) defined according to RECIST criteria
Secondary outcome [4] 0 0
To estimate duration of response for the ZD1839/Nolvadex and placebo/Nolvadex treatments in each strata and overall
Timepoint [4] 0 0
Duration of response (CR and PR)
Secondary outcome [5] 0 0
To compare overall survival between the ZD1839/Nolvadex and placebo/Nolvadex in each strata
Timepoint [5] 0 0
Overall survival
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Time to progression (progressive disease or death), duration of response (CR and PR)
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Objective tumour response (OR) defined according to RECIST criteria
Secondary outcome [8] 0 0
To compare the safety and tolerability of ZD1839/Nolvadex to placebo/Nolvadex
Timepoint [8] 0 0
Safety (frequency and severity of adverse events)
Secondary outcome [9] 0 0
To determine steady-state plasma trough concentrations of tamoxifen in all patients and to compare between the ZD1839/Nolvadex and placebo/Nolvadex treatment arms
Timepoint [9] 0 0
Tamoxifen (Cmin) steady-state plasma concentration
Secondary outcome [10] 0 0
To determine steady-state plasma trough concentrations of ZD1839 and relate values to historical data
Timepoint [10] 0 0
ZD1839 (Cmin) steady-state plasma concentration
Secondary outcome [11] 0 0
To relate steady-state plasma trough concentrations of ZD1839 to demographic, response, and safety variables
Timepoint [11] 0 0
ZD1839 (Cmin) steady-state plasma concentration
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
FACT-B questionnaire, FBSI (FACT-B Symptom Index)
Secondary outcome [13] 0 0
To investigate subject hospital resource use and health status
Timepoint [13] 0 0
Hospitalisations and EQ-5D
Secondary outcome [14] 0 0
Characterization of specific adverse events
Timepoint [14] 0 0
Characterization of adverse events such as alopecia, rash and diarrhea
Secondary outcome [15] 0 0
To obtain tumour tissue for biologic studies in this patient population
Timepoint [15] 0 0
ER receptor, ErbB-1 &2 (immunohistochemistry) and other biological markers including Her2/neu, AIB1

Eligibility
Key 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
Minimum age
18 Years
Maximum age
130 Years
Sex
Females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2015
Sample size
Target
Accrual to date
Final
317
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Bentleigh East
Recruitment hospital [2] 0 0
Research Site - Newcastle
Recruitment hospital [3] 0 0
Research Site - Randwick
Recruitment hospital [4] 0 0
Research Site - Westmead
Recruitment hospital [5] 0 0
Research Site - Wodonga
Recruitment postcode(s) [1] 0 0
- Bentleigh East
Recruitment postcode(s) [2] 0 0
- Newcastle
Recruitment postcode(s) [3] 0 0
- Randwick
Recruitment postcode(s) [4] 0 0
- Westmead
Recruitment postcode(s) [5] 0 0
- Wodonga
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
Argentina
State/province [4] 0 0
Bahía Blanca
Country [5] 0 0
Argentina
State/province [5] 0 0
Ciudad de Buenos Aires
Country [6] 0 0
Argentina
State/province [6] 0 0
Córdoba
Country [7] 0 0
Argentina
State/province [7] 0 0
El Palomar
Country [8] 0 0
Argentina
State/province [8] 0 0
Resistencia
Country [9] 0 0
Argentina
State/province [9] 0 0
Rosario
Country [10] 0 0
Argentina
State/province [10] 0 0
San Miguel de Tucuman
Country [11] 0 0
Argentina
State/province [11] 0 0
Santa Fe
Country [12] 0 0
Argentina
State/province [12] 0 0
Vicente Lopez
Country [13] 0 0
Belgium
State/province [13] 0 0
Brussels
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Belgium
State/province [15] 0 0
Wilrijk
Country [16] 0 0
Brazil
State/province [16] 0 0
Belo Horizonte
Country [17] 0 0
Brazil
State/province [17] 0 0
Curitiba
Country [18] 0 0
Brazil
State/province [18] 0 0
Porto Alegre
Country [19] 0 0
Brazil
State/province [19] 0 0
Sao Paulo
Country [20] 0 0
Brazil
State/province [20] 0 0
São Paulo
Country [21] 0 0
Canada
State/province [21] 0 0
Alberta
Country [22] 0 0
Canada
State/province [22] 0 0
New Brunswick
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec
Country [25] 0 0
Denmark
State/province [25] 0 0
Herlev
Country [26] 0 0
France
State/province [26] 0 0
Lyon Cedex 08
Country [27] 0 0
France
State/province [27] 0 0
Mougins
Country [28] 0 0
France
State/province [28] 0 0
Poitiers
Country [29] 0 0
France
State/province [29] 0 0
Rouen
Country [30] 0 0
Germany
State/province [30] 0 0
Frankfurt
Country [31] 0 0
Germany
State/province [31] 0 0
Jena
Country [32] 0 0
Germany
State/province [32] 0 0
Kiel
Country [33] 0 0
Germany
State/province [33] 0 0
München
Country [34] 0 0
Germany
State/province [34] 0 0
Trier
Country [35] 0 0
South Africa
State/province [35] 0 0
Durban
Country [36] 0 0
South Africa
State/province [36] 0 0
Johannesburg
Country [37] 0 0
South Africa
State/province [37] 0 0
Klerksdorp
Country [38] 0 0
South Africa
State/province [38] 0 0
Observatory
Country [39] 0 0
Spain
State/province [39] 0 0
Barcelona
Country [40] 0 0
Spain
State/province [40] 0 0
Córdoba
Country [41] 0 0
Spain
State/province [41] 0 0
Madrid
Country [42] 0 0
Spain
State/province [42] 0 0
Majadahonda
Country [43] 0 0
Spain
State/province [43] 0 0
Zaragoza
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Colchester
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Dundee
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Manchester
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00229697
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AstraZeneca Iressa Medical Science Director, MD
Address 0 0
AstraZeneca
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries