Breast Neoplasms
Conditions
Keywords
Breast cancer, metastatic breast cancer
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.
Interventions
DRUGGefitinib
DRUGTamoxifen
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 130 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Strata 1: To compare the time to progression between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex) | 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) | Overall clinical benefit rate: Complete Response, Partial Response or Stable Disease > 24weeks after each combination |
Secondary
| Measure | Time frame |
|---|---|
| To compare the objective response rate between ZD1839/Nolvadex and placebo/Nolvadex in each strata and overall | 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 | Duration of response (CR and PR) |
| To compare overall survival between the ZD1839/Nolvadex and placebo/Nolvadex in each strata | 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 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 | Objective tumour response (OR) defined according to RECIST criteria |
| To compare the safety and tolerability of ZD1839/Nolvadex to placebo/Nolvadex | Safety (frequency and severity of adverse events) |
| To compare the clinical benefit rate between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex) in Strata 1 and overall | 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 determine steady-state plasma trough concentrations of ZD1839 and relate values to historical data | ZD1839 (Cmin) steady-state plasma concentration |
| To relate steady-state plasma trough concentrations of ZD1839 to demographic, response, and safety variables | 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 | FACT-B questionnaire, FBSI (FACT-B Symptom Index) |
| To investigate subject hospital resource use and health status | Hospitalisations and EQ-5D |
| Characterization of specific adverse events | Characterization of adverse events such as alopecia, rash and diarrhea |
| To obtain tumour tissue for biologic studies in this patient population | ER receptor, ErbB-1 &2 (immunohistochemistry) and other biological markers including Her2/neu, AIB1 |
| To determine steady-state plasma trough concentrations of tamoxifen in all patients and to compare between the ZD1839/Nolvadex and placebo/Nolvadex treatment arms | Tamoxifen (Cmin) steady-state plasma concentration |
| To compare time to progression between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex) in Strata 2 and overall | Time to progression (progressive disease or death) |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Denmark, France, Germany, South Africa, Spain, United Kingdom, United States
Outcome results
None listed