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

Breast Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00229697
• Other study ID #: 1839IL/0225
• Secondary ID: D7917C00225
• Status: Completed
• Phase: Phase 2
• First received: September 28, 2005
• Last updated: October 2, 2015
• Start date: October 2003
• Est. completion date: June 2015

Study information

• Verified date: October 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00069290

Recruitment information / eligibility

• Status: Completed
• Enrollment: 317
• Est. completion date: June 2015
• Est. primary completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 130 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Gefitinib

• Tamoxifen

Locations

Country	Name	City	State
Argentina	Research Site	Bahía Blanca
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Córdoba
Argentina	Research Site	El Palomar
Argentina	Research Site	Resistencia
Argentina	Research Site	Rosario
Argentina	Research Site	San Miguel de Tucuman
Argentina	Research Site	Santa Fe
Argentina	Research Site	Vicente Lopez
Australia	Research Site	Bentleigh East
Australia	Research Site	Newcastle
Australia	Research Site	Randwick
Australia	Research Site	Westmead
Australia	Research Site	Wodonga
Belgium	Research Site	Brussels
Belgium	Research Site	Leuven
Belgium	Research Site	Wilrijk
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Curitiba
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Saint John	New Brunswick
Canada	Research Site	Toronto	Ontario
Denmark	Research Site	Herlev
France	Research Site	Lyon Cedex 08
France	Research Site	Mougins
France	Research Site	Poitiers
France	Research Site	Rouen
Germany	Research Site	Frankfurt
Germany	Research Site	Jena
Germany	Research Site	Kiel
Germany	Research Site	München
Germany	Research Site	Trier
South Africa	Research Site	Durban
South Africa	Research Site	Johannesburg
South Africa	Research Site	Klerksdorp
South Africa	Research Site	Observatory
Spain	Research Site	Barcelona
Spain	Research Site	Córdoba
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Zaragoza
United Kingdom	Research Site	Colchester
United Kingdom	Research Site	Dundee
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Nottingham
United States	Research Site	Berkeley	California
United States	Research Site	New York	New York
United States	Research Site	Palm Springs	California
United States	Research Site	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Denmark,  France,  Germany,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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	No
Secondary	To estimate duration of response for the ZD1839/Nolvadex and placebo/Nolvadex treatments in each strata and overall		Duration of response (CR and PR)	No
Secondary	To compare overall survival between the ZD1839/Nolvadex and placebo/Nolvadex in each strata		Overall survival	No
Secondary	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)	No
Secondary	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	No
Secondary	To compare the safety and tolerability of ZD1839/Nolvadex to placebo/Nolvadex		Safety (frequency and severity of adverse events)	Yes
Secondary	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	No
Secondary	To determine steady-state plasma trough concentrations of ZD1839 and relate values to historical data		ZD1839 (Cmin) steady-state plasma concentration	No
Secondary	To relate steady-state plasma trough concentrations of ZD1839 to demographic, response, and safety variables		ZD1839 (Cmin) steady-state plasma concentration	No
Secondary	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)	No
Secondary	To investigate subject hospital resource use and health status		Hospitalisations and EQ-5D	No
Secondary	Characterization of specific adverse events		Characterization of adverse events such as alopecia, rash and diarrhea	Yes
Secondary	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	No

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