Breast NeoplasmsPhase 2NCT00229697
Phase II Metastatic ER+/PgR+ Nolvadex +/- Iressa Study
A Phase 2 study testing Gefitinib and Tamoxifen in people with Breast Neoplasms, run by AstraZeneca at 55 sites in 12 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 130 years, women only
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- Gefitinib and Tamoxifen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 317 participants
- Where
- 55 sitesin 12 countries
- Study dates
- Oct 2003to Jun 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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,
Show all 9Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
55 sites in 12 countries.
55 sites in 12 countries
Argentina9 sites
Research Site
Bahía Blanca
Research Site
Ciudad de Buenos Aires
Research Site
Córdoba
Research Site
El Palomar
Research Site
Resistencia
Research Site
Rosario
Research Site
San Miguel de Tucumán
Research Site
Santa Fe
Research Site
Vicente López
Canada7 sites
Research Site
Calgary, Alberta
Research Site
Edmonton, Alberta
Research Site
Montreal, Quebec
Research Site
Ottawa, Ontario
Research Site
Québec, Quebec
Research Site
Saint John, New Brunswick
Research Site
Toronto, Ontario
Australia5 sites
Research Site
Bentleigh East
Research Site
Newcastle
Research Site
Randwick
Research Site
Westmead
Research Site
Wodonga
Germany5 sites
Research Site
Frankfurt
Research Site
Jena
Research Site
Kiel
Research Site
München
Research Site
Trier
Spain5 sites
Research Site
Barcelona
Research Site
Córdoba
Research Site
Madrid
Research Site
Majadahonda
Research Site
Zaragoza
United States4 sites
Research Site
Berkeley, California
Research Site
New York, New York
Research Site
Palm Springs, California
Research Site
St Louis, Missouri
Brazil4 sites
Research Site
Belo Horizonte
Research Site
Curitiba
Research Site
Porto Alegre
Research Site
São Paulo
France4 sites
Research Site
Lyon
Research Site
Mougins
Research Site
Poitiers
Research Site
Rouen
South Africa4 sites
Research Site
Durban
Research Site
Johannesburg
Research Site
Klerksdorp
Research Site
Observatory
United Kingdom4 sites
Research Site
Colchester
Research Site
Dundee
Research Site
Manchester
Research Site
Nottingham
Belgium3 sites
Research Site
Brussels
Research Site
Leuven
Research Site
Wilrijk
About this study
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
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.
- Conditions
- Breast Neoplasms
- Being tested
- Gefitinib, Tamoxifen
- Keywords
- Breast cancer, metastatic breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GefitinibDrug
Also called Iressa
TamoxifenDrug
Also called Nolvadex
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | ZD1839 + Nolvadex Receives: Drug: Gefitinib; Drug: Tamoxifen |
| 2 | Other | Nolvadex + placebo Receives: Drug: Tamoxifen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Strata 1: To compare the time to progression between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex)
Measured: 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)
Measured: Overall clinical benefit rate: Complete Response, Partial Response or Stable Disease > 24weeks after each combination
Secondary outcomes (15)
To compare the clinical benefit rate between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex) in Strata 1 and overall
Measured: 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 compare time to progression between 2 treatment arms (ZD1839/Nolvadex vs placebo/Nolvadex) in Strata 2 and overall
Measured: Time to progression (progressive disease or death)
To compare the objective response rate between ZD1839/Nolvadex and placebo/Nolvadex in each strata and overall
Measured: Objective tumour response (OR) defined according to RECIST criteria
To estimate duration of response for the ZD1839/Nolvadex and placebo/Nolvadex treatments in each strata and overall
Measured: Duration of response (CR and PR)
To compare overall survival between the ZD1839/Nolvadex and placebo/Nolvadex in each strata
Measured: 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
Measured: Time to progression (progressive disease or death), duration of response (CR and PR)
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
Measured: Objective tumour response (OR) defined according to RECIST criteria
To compare the safety and tolerability of ZD1839/Nolvadex to placebo/Nolvadex
Measured: 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
Measured: Tamoxifen (Cmin) steady-state plasma concentration
To determine steady-state plasma trough concentrations of ZD1839 and relate values to historical data
Measured: ZD1839 (Cmin) steady-state plasma concentration
To relate steady-state plasma trough concentrations of ZD1839 to demographic, response, and safety variables
Measured: 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
Measured: FACT-B questionnaire, FBSI (FACT-B Symptom Index)
To investigate subject hospital resource use and health status
Measured: Hospitalisations and EQ-5D
Characterization of specific adverse events
Measured: Characterization of adverse events such as alopecia, rash and diarrhea
To obtain tumour tissue for biologic studies in this patient population
Measured: ER receptor, ErbB-1 &2 (immunohistochemistry) and other biological markers including Her2/neu, AIB1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2005 (estimated)
- Study startOct 2003
- Primary completionDec 2006
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 317 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- AstraZeneca Iressa Medical Science Director, MD, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00229697
- Sponsor's protocol ID
- 1839IL/0225
- Other IDs
- D7917C00225
- Status last verified
- Oct 2015
- First submitted
- 28 Sep 2005
- Last updated
- 5 Oct 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00229697
- Acronym / sponsor ID
- 1839IL/0225
- Conditions
- Breast Neoplasms
- Keywords
- Breast cancer, metastatic breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 317 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Oct 2003
- Primary completion
- Dec 2006 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 30 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Gefitinib, Drug: TamoxifenZD1839 + Nolvadex |
| 2 | Other | Drug: TamoxifenNolvadex + placebo |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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,
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GefitinibAlso: Iressa | Drug | 1 |
| TamoxifenAlso: Nolvadex | Drug | 1, 2 |
Primary outcome
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)
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
15 secondary outcomes
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
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)
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
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)
To compare overall survival between the ZD1839/Nolvadex and placebo/Nolvadex in each strata
Time frame: 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 frame: Time to progression (progressive disease or death), duration of response (CR and PR)
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
To compare the safety and tolerability of ZD1839/Nolvadex to placebo/Nolvadex
Time frame: 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
Time frame: Tamoxifen (Cmin) steady-state plasma concentration
To determine steady-state plasma trough concentrations of ZD1839 and relate values to historical data
Time frame: ZD1839 (Cmin) steady-state plasma concentration
To relate steady-state plasma trough concentrations of ZD1839 to demographic, response, and safety variables
Time frame: 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
Time frame: FACT-B questionnaire, FBSI (FACT-B Symptom Index)
To investigate subject hospital resource use and health status
Time frame: Hospitalisations and EQ-5D
Characterization of specific adverse events
Time frame: Characterization of adverse events such as alopecia, rash and diarrhea
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2015.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
AstraZeneca Iressa Medical Science Director, MD study director
AstraZeneca
55 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gefitinib and Tamoxifen in people with Breast Neoplasms, run by AstraZeneca at 55 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 55 sites in Argentina, Canada, Australia, Germany, Spain and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2015.