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) [ Time Frame: Time to progression (progressive disease or death; equivalent to progression-free survival) ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
To compare overall survival between the ZD1839/Nolvadex and placebo/Nolvadex in each strata [ Time Frame: Overall survival ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
To compare the safety and tolerability of ZD1839/Nolvadex to placebo/Nolvadex [ Time Frame: Safety (frequency and severity of adverse events) ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
To determine steady-state plasma trough concentrations of ZD1839 and relate values to historical data [ Time Frame: ZD1839 (Cmin) steady-state plasma concentration ] [ Designated as safety issue: No ]
To relate steady-state plasma trough concentrations of ZD1839 to demographic, response, and safety variables [ Time Frame: ZD1839 (Cmin) steady-state plasma concentration ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
To investigate subject hospital resource use and health status [ Time Frame: Hospitalisations and EQ-5D ] [ Designated as safety issue: No ]
Characterization of specific adverse events [ Time Frame: Characterization of adverse events such as alopecia, rash and diarrhea ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]


Enrollment:	317
Study Start Date:	October 2003
Estimated Study Completion Date:	December 2015
Primary Completion Date:	December 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 ZD1839 + Nolvadex	Drug: Gefitinib Other Name: Iressa Drug: Tamoxifen Other Name: Nolvadex
2 Nolvadex + placebo	Drug: Tamoxifen 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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Sponsors and Collaborators

AstraZeneca

Investigators


Study Director:	AstraZeneca Iressa Medical Science Director, MD	AstraZeneca

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

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:	January 9, 2015
Health Authority:	United States: Food and Drug Administration

Keywords provided by AstraZeneca:


Breast cancer metastatic breast cancer

Additional relevant MeSH terms:


Tamoxifen Antineoplastic Agents Antineoplastic Agents, Hormonal Bone Density Conservation Agents Estrogen Antagonists Estrogen Receptor Modulators	Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Pharmacologic Actions Physiological Effects of Drugs Selective Estrogen Receptor Modulators Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015