Clinical trial NCT00229697: Phase II Metastatic ER+/PgR+ Nolvadex +/- Iressa Study
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Neoplasms
Keywords: Breast cancer
metastatic breast cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2005-09-30
Enrollment: 317
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Strata 1: To compare the time to progression between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex)
timeFrame: Time to progression (progressive disease or death; equivalent to progression-free survival)
measure: Strata 2: To compare the clinical benefit rate between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex)
timeFrame: Overall clinical benefit rate: Complete Response, Partial Response or Stable Disease > 24weeks after each combination
Secondary outcomes:
measure: To compare the clinical benefit rate between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex) in Strata 1 and overall
timeFrame: Overall clinical benefit rate: Complete Response, Partial Response or Stable Disease >24 weeks after each combination. Objective tumour resp defined according to RECIST criteria
measure: To compare time to progression between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex) in Strata 2 and overall
timeFrame: Time to progression (progressive disease or death)
measure: To compare the objective response rate between ZD1839/Nolvadex and placebo/Nolvadex in each strata and overall
timeFrame: Objective tumour response (OR) defined according to RECIST criteria
measure: To estimate duration of response for the ZD1839/Nolvadex and placebo/Nolvadex treatments in each strata and overall
timeFrame: Duration of response (CR and PR)
measure: To compare overall survival between the ZD1839/Nolvadex and placebo/Nolvadex in each strata
timeFrame: Overall survival
measure: 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
timeFrame: Time to progression (progressive disease or death), duration of response (CR and PR)
measure: 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
timeFrame: Objective tumour response (OR) defined according to RECIST criteria
measure: To compare the safety and tolerability of ZD1839/Nolvadex to placebo/Nolvadex
timeFrame: Safety (frequency and severity of adverse events)
measure: To determine steady-state plasma trough concentrations of tamoxifen in all patients and to compare between the ZD1839/Nolvadex and placebo/Nolvadex treatment arms
timeFrame: Tamoxifen (Cmin) steady-state plasma concentration
measure: To determine steady-state plasma trough concentrations of ZD1839 and relate values to historical data
timeFrame: ZD1839 (Cmin) steady-state plasma concentration
measure: To relate steady-state plasma trough concentrations of ZD1839 to demographic, response, and safety variables
timeFrame: ZD1839 (Cmin) steady-state plasma concentration
measure: 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
timeFrame: FACT-B questionnaire, FBSI (FACT-B Symptom Index)
measure: To investigate subject hospital resource use and health status
timeFrame: Hospitalisations and EQ-5D
measure: Characterization of specific adverse events
timeFrame: Characterization of adverse events such as alopecia, rash and diarrhea
measure: To obtain tumour tissue for biologic studies in this patient population
timeFrame: ER receptor, ErbB-1 &2 (immunohistochemistry) and other biological markers including Her2/neu, AIB1
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: Research Site
state: California
city: Palm Springs
country: United States
facility: Research Site
state: California
city: St. Louis
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Bahía Blanca
country: Argentina
facility: Research Site
city: Ciudad de Buenos Aires
country: Argentina
facility: Research Site
city: Córdoba
country: Argentina
facility: Research Site
city: El Palomar
country: Argentina
facility: Research Site
city: Resistencia
country: Argentina
facility: Research Site
city: Rosario
country: Argentina
facility: Research Site
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
city: Santa Fe
country: Argentina
facility: Research Site
city: Vicente Lopez
country: Argentina
facility: Research Site
city: Bentleigh East
country: Australia
facility: Research Site
city: Newcastle
country: Australia
facility: Research Site
city: Randwick
country: Australia
facility: Research Site
city: Westmead
country: Australia
facility: Research Site
city: Wodonga
country: Australia
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Wilrijk
country: Belgium
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Saint John
country: Canada
facility: Research Site
state: New Brunswick
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Herlev
country: Denmark
facility: Research Site
city: Lyon Cedex 08
country: France
facility: Research Site
city: Mougins
country: France
facility: Research Site
city: Poitiers
country: France
facility: Research Site
city: Rouen
country: France
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Jena
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Trier
country: Germany
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Klerksdorp
country: South Africa
facility: Research Site
city: Observatory
country: South Africa
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Córdoba
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Colchester
country: United Kingdom
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: AstraZeneca Iressa Medical Science Director, MD
role: STUDY_DIRECTOR
References: