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Trial registered on ANZCTR


Registration number
ACTRN12607000013460
Ethics application status
Approved
Date submitted
14/11/2006
Date registered
8/01/2007
Date last updated
19/05/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
ANZ 0301 / BCIRG 103 (1839 IL / 0219) : Presurgical Study Evaluating IRESSA
Scientific title
A phase II, presurgical study to evaluate molecular alterations that occur in human breast cancer tissue and normal skin after short term exposure to ZD1839 (IRESSA) and to correlate these alterations with pharmacokinetic parameters.
Secondary ID [1] 259762 0
nil
Universal Trial Number (UTN)
Trial acronym
ANZ 0301 / BCIRG 103 (1839IL/0219)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Invasive Breast Cancer 1514 0
Condition category
Condition code
Cancer 1612 1612 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Eligible patients will be registered to receive the tyrosine kinase inhibitor, ZD1839 (gefitinib; IRESSA) for a minimum of 14 days to a maximum of 45 days; commencing within the 8 days following registration and ceasing 24 hours prior to the time of definitive surgery. No more than 28 days should elapse between the initial breast cancer diagnosis and the first dose of ZD1839 (IRESSA). Each patient should receive a minimum of 10 consecutive days of treatment with ZD1839 (IRESSA) prior to the definitive surgery date.

During the treatment period, ZD1839 (IRESSA) will be administered orally, once daily, in a 250 mg dose.

Follow up of patients will continue beyond definitive surgery with the last planned clinic visit scheduled for 30 days after the last administration of ZD1839 (IRESSA). In the event that related adverse events or serious adverse events are ongoing at the last planned visit, patient follow up will continue as clinically indicated until the event/s resolve or, in the Investigator’s opinion, are unlikely to resolve due to the nature of the condition and/or the patient’s underlying disease.
Intervention code [1] 1445 0
Treatment: Drugs
Comparator / control treatment
No comparator.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 2223 0
To identify the molecular alterations which occur in human breast cancer tissue after short term exposure to ZD1839 (IRESSA). Short term exposure to ZD1839 (IRESSA) is defined as a maximum of 45 days (range 14 – 45 days). Molecular alterations occurring due to ZD1839 (IRESSA) exposure will be identified by analyses of tumour tissue samples (core needle or incisional biopsy) and skin punch biopsies collected.
Timepoint [1] 2223 0
At the time of initial diagnosis (baseline) and again at the time of definitive surgery.
Primary outcome [2] 2224 0
Pharmacokinetic and pharmacodynamic analyses will be conducted on assays of plasma samples collected from the patients.
Timepoint [2] 2224 0
At baseline, immediately prior to the last dose of ZD1839 (IRESSA), and again 24 hours after the last dose of ZD1839 (IRESSA).
Secondary outcome [1] 3877 0
For all patients:
• To evaluate the molecular effects of short term ZD1839 exposure in normal skin tissue and on Epidermal Growth Factor Receptor (EGFR) signalling pathways in non-tumour cells (skin tissue).
• To correlate the pharmacokinetic parameters with molecular alterations detected in breast cancer tissue and normal skin following study treatment.
• To evaluate the tolerability and safety of short term exposure to a daily oral single dose of 250 mg ZD1839 administration.
Timepoint [1] 3877 0
Pharmacokinetic parameters will be determined from assays of plasma samples (collected at baseline, immediately prior to, and 24 hours after, the last dose of ZD1839 (IRESSA).
Secondary outcome [2] 3878 0
For patients having consented to the optional substudy (tumour tissue collection):
• To determine intratumoural concentrations of ZD1839 and correlate these with pharmacokinetic parameters and molecular alterations detected in breast cancer tissue.
Timepoint [2] 3878 0
Intratumoural concentrations of ZD1839 and pharmacokinetic parameters will be determined from assays of plasma samples (collected at baseline, immediately prior to, and 24 hours after, the last dose of ZD1839 (IRESSA).

Eligibility
Key inclusion criteria
1. Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements. 2. Histologically proven invasive breast cancer (adenocarcinoma) through either a core needle biopsy or an incisional biopsy. An excisional biopsy will not be allowed. 3. Tumour must be confined to either the breast or to the breast and ipsilateral axilla. Patients must have a tumour size of >= 2 cm (T1 with T=2cm, T2 - T3). Patient can have either clinically positive (N1) or clinically negative axillary nodes (N0). 4. Patient must provide tumour tissue from four (4) core needle biopsies (or the equivalent with respect to tumour volume acquired from an incisional biopsy) for the molecular analyses being performed by the designated UCLA laboratory. 5. Patient must provide normal skin tissue from two punch biopsies for analyses being performed by the designated UCLA laboratory. 6. Patient must provide a baseline plasma sample for the pharmacokinetic analysis. 7. Age >=18 years. 8. Karnofsky Performance status index >= 80%. 9. Laboratory requirements: (within 28 days prior to registration)a. Hematology:i. Neutrophils >= 1.5 x 109/L ii. Platelets >= 100 x 109/L iii. Hemoglobin >= 10 g/dLb. Hepatic function: i. Total bilirubin <= 1 UNL (patients with a well documented history of Gilbert's Syndrome are eligible)ii. ASAT (SGOT) and ALAT (SGPT) <= 2.5 UNLiii. Alkaline phosphatase <= 5 UNLc. Renal function:i. Creatinine <= 175 µmol/L (2 mg/dL)10. Not more than 28 days from the time of the initial diagnosis and 8 days from registration to the first dose of ZD1839 shall elapse. 11. Patients must be accessible for treatment and the 30-day follow-up. 12. Negative pregnancy test (urine or serum) within 7 days prior to registration for all women of childbearing potential.
Minimum age
18 Years
Maximum age
Not stated
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior or concurrent systemic anticancer therapy for cancer (immunotherapy, hormonotherapy, biological therapy, or chemotherapy). 2. Prior or concurrent ipsilateral radiation therapy for invasive or non-invasive breast cancer. 3. Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment. 4. Any T1 (with the exception of T1 with T=2 cm) or T4 or N2 or known N3 or M1 breast cancer.5. Other serious illness or medical condition:a. Concurrent congestive heart failure or unstable angina pectoris, uncontrolled hypertension or high-risk uncontrolled arrhythmias, b. History of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent,c. Active uncontrolled infection, d. Pre-existing or concurrent interstitial lung disease. 6. Past or current history of neoplasm other than breast carcinoma, except fora. curatively treated non-melanoma skin cancer, b. in situ carcinoma of the cervix, or c. other cancer curatively treated and with no evidence of disease for at least 5 years.7. Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment should be stopped at least 4 weeks prior to registration. 8. Concurrent treatment with other experimental drugs or treatment with investigational drugs within 30 days of registration. 9. Prior hormonal therapy with any hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulators (SERMs), either for osteoporosis or prevention. 10. Currently receiving drugs with known significant CYP 3A4 inhibitory effects (such as ketoconazole, itraconazole, troleandomycin, erythromycin, diltiazem, verapamil, ritonavir, indinavir).11. Concurrent administration with inducers of CYP 3A4 may result in a lower exposure to ZD1839 and are therefore not allowed (eg. phenytoin, carbamazepine, rifampicin, barbiturates, or St. John’s Wort).12. Known allergy reactions to ZD1839 or excipients used in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2003
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
59
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 1757 0
Self funded/Unfunded
Name [1] 1757 0
Australian New Zealand Breast Cancer Trials Group
Country [1] 1757 0
Australia
Funding source category [2] 1758 0
Self funded/Unfunded
Name [2] 1758 0
Breast Cancer International Research Group
Country [2] 1758 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca Pharmaceuticals
Address
to be confirmed
Country
Australia
Secondary sponsor category [1] 1557 0
Other Collaborative groups
Name [1] 1557 0
Australian New Zealand Breast Cancer Trials Group (ANZ BCTG)
Address [1] 1557 0
Locked Bag 7, HRMC, NSW, 2310
Country [1] 1557 0
Australia
Secondary sponsor category [2] 1558 0
Other Collaborative groups
Name [2] 1558 0
Breast Cancer International Research Group (BCIRG)
Address [2] 1558 0
Edmonton Office
Suite 1100
9925-109 Street
Edmonton, Alberta T5K 2J8, Canada
Country [2] 1558 0
Australia

Ethics approval
Ethics application status
Approved

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27379 0
Address 27379 0
Country 27379 0
Phone 27379 0
Fax 27379 0
Email 27379 0
Contact person for public queries
Name 10634 0
Administrative Officer, Data Management Department
Address 10634 0
ANZ BCTG Operations Office
Department of Surgical Oncology
Locked Bag 7
Hunter Region Mail Centre
Newcastle, NSW 231
Country 10634 0
Australia
Phone 10634 0
+61 2 4925 3068
Fax 10634 0
+ 61 2 4985 0141
Email 10634 0
enquiries@anzbctg.newcastle.edu.au
Contact person for scientific queries
Name 1562 0
Professor John F Forbes
Address 1562 0
ANZ BCTG Operations Office
Department of Surgical Oncology
Locked Bag 7
Hunter Region Mail Centre
Newcastle, NSW 231
Country 1562 0
Australia
Phone 1562 0
+ 61 2 4985 0113
Fax 1562 0
+ 61 2 4960 1539
Email 1562 0
enquiries@anzbctg.newcastle.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.