Phase II Metastatic ER+/PgR+ Nolvadex +/- Iressa Study - Full Text View

Purpose

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.

Condition	Intervention	Phase
Breast Neoplasms	Drug: Gefitinib Drug: Tamoxifen	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Tamoxifen Tamoxifen citrate Gefitinib

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

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 Measures:

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

Enrollment:	274
Study Start Date:	October 2003
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Intervention Details:

Other Name: Iressa

Other Name: Nolvadex

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00229697

Show 62 Study Locations

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:

AstraZeneca Iressa Medical Science Director, MD

AstraZeneca

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00229697 History of Changes
Obsolete Identifiers:	NCT00069290
Other Study ID Numbers:	1839IL/0225, D7917C00225
Study First Received:	September 28, 2005
Last Updated:	April 30, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by AstraZeneca:

Breast cancer
metastatic breast cancer

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Tamoxifen
Gefitinib
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents
Estrogen Antagonists
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013