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

Phase 2

Completed

• Conditions: Breast Neoplasms
• Interventions: Drug: Gefitinib; Drug: Tamoxifen

• Registration Number: NCT00229697
• Lead Sponsor: AstraZeneca

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2003-10
• Study First Submitted: 2005-09-28
• Study First Submitted QC: 2005-09-28
• Study First Posted: 2005-09-30
• Primary Completion: 2006-12
• Study Completion: 2015-06
• Status Verified: 2015-10
• Last Update Submitted: 2015-10-02
• Last Update Posted: 2015-10-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 317

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Gefitinib	ZD1839 + Nolvadex
1	Tamoxifen	ZD1839 + Nolvadex
2	Tamoxifen	Nolvadex + placebo

Primary Outcome Measures

Name	Time	Method
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)
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

Secondary Outcome Measures

Name	Time	Method
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
To estimate duration of response for the ZD1839/Nolvadex and placebo/Nolvadex treatments in each strata and overall	Duration of response (CR and PR)
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)
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
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
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
To compare overall survival between the ZD1839/Nolvadex and placebo/Nolvadex in each strata	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 to progression (progressive disease or death), duration of response (CR and PR)
To compare the safety and tolerability of ZD1839/Nolvadex to placebo/Nolvadex	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	Tamoxifen (Cmin) steady-state plasma concentration
To determine steady-state plasma trough concentrations of ZD1839 and relate values to historical data	ZD1839 (Cmin) steady-state plasma concentration
To relate steady-state plasma trough concentrations of ZD1839 to demographic, response, and safety variables	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	FACT-B questionnaire, FBSI (FACT-B Symptom Index)
To investigate subject hospital resource use and health status	Hospitalisations and EQ-5D
Characterization of specific adverse events	Characterization of adverse events such as alopecia, rash and diarrhea

Trial Locations

Locations (1)

Research Site; 🇬🇧 Nottingham, United Kingdom