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

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT00229697
Collaborator
(none)
317
Enrollment
56
Locations
2
Arms
140
Duration (Months)
5.7
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
317 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, 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
Study Start Date :
Oct 1, 2003
Actual Primary Completion Date :
Dec 1, 2006
Actual Study Completion Date :
Jun 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

ZD1839 + Nolvadex

Drug: Gefitinib
Other Names:
  • Iressa

    • Drug: Tamoxifen
    Other Names:
  • Nolvadex

    		•
    Other: 2

    Nolvadex + placebo

    Drug: Tamoxifen
    Other Names:
  • Nolvadex

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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)]

    2. 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

    1. 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]

    2. 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)]

    3. 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]

    4. To estimate duration of response for the ZD1839/Nolvadex and placebo/Nolvadex treatments in each strata and overall [Duration of response (CR and PR)]

    5. To compare overall survival between the ZD1839/Nolvadex and placebo/Nolvadex in each strata [Overall survival]

    6. 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)]

    7. 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]

    8. To compare the safety and tolerability of ZD1839/Nolvadex to placebo/Nolvadex [Safety (frequency and severity of adverse events)]

    9. 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]

    10. To determine steady-state plasma trough concentrations of ZD1839 and relate values to historical data [ZD1839 (Cmin) steady-state plasma concentration]

    11. To relate steady-state plasma trough concentrations of ZD1839 to demographic, response, and safety variables [ZD1839 (Cmin) steady-state plasma concentration]

    12. 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)]

    13. To investigate subject hospital resource use and health status [Hospitalisations and EQ-5D]

    14. Characterization of specific adverse events [Characterization of adverse events such as alopecia, rash and diarrhea]

    15. 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]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Research Site Berkeley California United States
    2 Research Site Palm Springs California United States
    3 Research Site St. Louis Missouri United States
    4 Research Site New York New York United States
    5 Research Site Bahía Blanca Argentina
    6 Research Site Ciudad de Buenos Aires Argentina
    7 Research Site Córdoba Argentina
    8 Research Site El Palomar Argentina
    9 Research Site Resistencia Argentina
    10 Research Site Rosario Argentina
    11 Research Site San Miguel de Tucuman Argentina
    12 Research Site Santa Fe Argentina
    13 Research Site Vicente Lopez Argentina
    14 Research Site Bentleigh East Australia
    15 Research Site Newcastle Australia
    16 Research Site Randwick Australia
    17 Research Site Westmead Australia
    18 Research Site Wodonga Australia
    19 Research Site Brussels Belgium
    20 Research Site Leuven Belgium
    21 Research Site Wilrijk Belgium
    22 Research Site Belo Horizonte Brazil
    23 Research Site Curitiba Brazil
    24 Research Site Porto Alegre Brazil
    25 Research Site Sao Paulo Brazil
    26 Research Site São Paulo Brazil
    27 Research Site Calgary Alberta Canada
    28 Research Site Edmonton Alberta Canada
    29 Research Site Saint John New Brunswick Canada
    30 Research Site Ottawa Ontario Canada
    31 Research Site Toronto Ontario Canada
    32 Research Site Montreal Quebec Canada
    33 Research Site Quebec Canada
    34 Research Site Herlev Denmark
    35 Research Site Lyon Cedex 08 France
    36 Research Site Mougins France
    37 Research Site Poitiers France
    38 Research Site Rouen France
    39 Research Site Frankfurt Germany
    40 Research Site Jena Germany
    41 Research Site Kiel Germany
    42 Research Site München Germany
    43 Research Site Trier Germany
    44 Research Site Durban South Africa
    45 Research Site Johannesburg South Africa
    46 Research Site Klerksdorp South Africa
    47 Research Site Observatory South Africa
    48 Research Site Barcelona Spain
    49 Research Site Córdoba Spain
    50 Research Site Madrid Spain
    51 Research Site Majadahonda Spain
    52 Research Site Zaragoza Spain
    53 Research Site Colchester United Kingdom
    54 Research Site Dundee United Kingdom
    55 Research Site Manchester United Kingdom
    56 Research Site Nottingham United Kingdom

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Study Director: AstraZeneca Iressa Medical Science Director, MD, AstraZeneca

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT00229697
    Other Study ID Numbers:
    • 1839IL/0225
    • D7917C00225
    • NCT00069290
    First Posted:
    Sep 30, 2005
    Last Update Posted:
    Oct 5, 2015
    Last Verified:
    Oct 1, 2015
    Keywords provided by AstraZeneca
    Breast cancer
    metastatic breast cancer
    Additional relevant MeSH terms:
    Breast Neoplasms
    Tamoxifen
    Gefitinib

    Study Results

    No Results Posted as of Oct 5, 2015