Overview

This trial is active, not recruiting.

Condition breast neoplasms
Treatments gefitinib, tamoxifen
Phase phase 2
Target EGFR
Sponsor AstraZeneca
Start date October 2003
End date December 2006
Trial size 317 participants
Trial identifier NCT00229697, 1839IL/0225, D7917C00225, NCT00069290

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
ZD1839 + Nolvadex
gefitinib Iressa
tamoxifen Nolvadex
(Other)
Nolvadex + placebo
tamoxifen Nolvadex

Primary Outcomes

Measure
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)
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

Secondary Outcomes

Measure
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
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)
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
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)
To compare overall survival between the ZD1839/Nolvadex and placebo/Nolvadex in each strata
time frame: 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)
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
To compare the safety and tolerability of ZD1839/Nolvadex to placebo/Nolvadex
time frame: 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
To determine steady-state plasma trough concentrations of ZD1839 and relate values to historical data
time frame: 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
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)
To investigate subject hospital resource use and health status
time frame: Hospitalisations and EQ-5D
Characterization of specific adverse events
time frame: 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

Eligibility Criteria

Female participants at least 18 years old.

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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in June 2015.
Information provided to ClinicalTrials.gov by AstraZeneca.