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

Condition(s) targeted: Breast Neoplasms

Intervention: Gefitinib (Drug); Tamoxifen (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: AstraZeneca

Official(s) and/or principal investigator(s):
AstraZeneca Iressa Medical Science Director, MD, Study Director, Affiliation: AstraZeneca

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.

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 design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome:

Strata 1: To compare the time to progression between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex)

Strata 2: To compare the clinical benefit rate between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex)

Secondary outcome:

To compare the clinical benefit rate between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex) in Strata 1 and overall

To compare time to progression between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex) in Strata 2 and overall

To compare the objective response rate between ZD1839/Nolvadex and placebo/Nolvadex in each strata and overall

To estimate duration of response for the ZD1839/Nolvadex and placebo/Nolvadex treatments in each strata and overall

To compare overall survival between the ZD1839/Nolvadex and placebo/Nolvadex in each strata

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

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

To compare the safety and tolerability of ZD1839/Nolvadex to placebo/Nolvadex

To determine steady-state plasma trough concentrations of tamoxifen in all patients and to compare between the ZD1839/Nolvadex and placebo/Nolvadex treatment arms

To determine steady-state plasma trough concentrations of ZD1839 and relate values to historical data

To relate steady-state plasma trough concentrations of ZD1839 to demographic, response, and safety variables

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

To investigate subject hospital resource use and health status

Characterization of specific adverse events

To obtain tumour tissue for biologic studies in this patient population

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

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

Research Site, Bahia Blanca, Argentina

Research Site, Cordoba, Argentina

Research Site, Santa Fe, Argentina

Research Site, Buenos Aires, Argentina

Research Site, Ciudad de Buenos Aires, Argentina

Research Site, Mendoza, Argentina

Research Site, Brussels, Belgium

Research Site, Leuven, Belgium

Research Site, Wilrijk, Belgium

Research Site, Quebec, Canada

Research Site, Santiago de Chile, Chile

Research Site, LYON, France

Research Site, CAEN CEDEX, France

Research Site, LYON CEDEX 08, France

Research Site, MOUGINS, France

Research Site, POITIERS, France

Research Site, ROUEN, France

Research Site, Mainz, Germany

Research Site, Frankfurt, Germany

Research Site, Jena, Germany

Research Site, Kiel, Germany

Research Site, München, Germany

Research Site, Trier, Germany

Research Site, Klerksdorp, South Africa

Research Site, Bloemfontein, South Africa

Research Site, Durban, South Africa

Research Site, Johannesburg, South Africa

Research Site, Lyttelton Manor, South Africa

Research Site, Observatory, South Africa

Research Site, Pietermaritzburg, South Africa

Research Site, Cape Town, South Africa

Research Site, George, South Africa

Research Site, Barcelona, Spain

Research Site, Córdoba, Spain

Research Site, Granada, Spain

Research Site, Madrid, Spain

Research Site, Sevilla, Spain

Research Site, Zaragoza, Spain

Research Site, Colchester, United Kingdom

Research Site, Dundee, United Kingdom

Research Site, Manchester, United Kingdom

Research Site, Nottingham, United Kingdom

Research Site, Swansea, United Kingdom

Research Site, Calgary, Alberta, Canada

Research Site, Edmonton, Alberta, Canada

Research Site, Berkeley, California, United States

Research Site, Montebello, California, United States

Research Site, Palm Springs, California, United States

Research Site, St. Louis, Missouri, United States

Research Site, Saint John, New Brunswick, Canada

Research Site, Lake Success, New York, United States

Research Site, New York, New York, United States

Research Site, Ottawa, Ontario, Canada

Research Site, Toronto, Ontario, Canada

Research Site, Mississauga, Ontario, Canada

Research Site, Curitiba, PR, Brazil

Research Site, Rio de Janeiro, RJ, Brazil

Research Site, Porto Alegre, RS, Brazil

Research Site, Sao Paulo, SP, Brazil

Research Site, Bentleigh East, Victoria, Australia

Research Site, Wodonga, Victoria, Australia

Research Site, Belo Horizonte, mg, Brazil

Starting date: October 2003
Ending date: April 2007
Last updated: November 2, 2007