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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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21 December 2021 |
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Main ID: |
EUCTR2006-000564-81-IT |
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Date of registration:
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17/12/2007 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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A randomised, multicenter open-label phase III study of neoadjuvant lapatinib, trastuzumab and their combination plus paclitaxel in women with HER2/ErbB2 positive primary breast cancer - Neoadjuv Lapat and/or Trastuz Treatm. Optimisation
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Scientific title:
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A randomised, multicenter open-label phase III study of neoadjuvant lapatinib, trastuzumab and their combination plus paclitaxel in women with HER2/ErbB2 positive primary breast cancer - Neoadjuv Lapat and/or Trastuz Treatm. Optimisation |
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Date of first enrolment:
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06/03/2008 |
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Target sample size:
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450 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-000564-81 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: yes
Placebo: no
Other: no
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Belgium
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France
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Germany
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Greece
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Hungary
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Italy
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Lithuania
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Spain
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Sweden
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United Kingdom
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Contacts
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Key inclusion & exclusion criteria
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Inclusion criteria:
1) Female gender; 2) Age >=18 years; 3) Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1 (See Appendix 2 ); 4) Histologically confirmed invasive breast cancer: - Primary tumour greater than 2 cm diameter, measured by mammography and echography, - Any N, - No evidence of metastasis (M0) (isolated supraclavicular node involvement allowed); 5) Over expression and/or amplification of HER2 in the invasive component of the primary tumour according to one of the following definitions [Wolff et al 2006] and confirmed by a certified laboratory prior to randomisation (See section 5.2): ? 3+ over expression by IHC (> 30% of invasive tumour cells); ? 2+ or 3+ (in 30% or less neoplastic cells) over expression by IHC AND in situ hybridization (FISH/CISH) test demonstrating HER2 gene amplification; ? HER2 gene amplification by FISH/CISH ( > 6 HER2 gene copies per nucleus, or a FISH ratio [HER2 gene copies to chromosome 17 signals] of > than 2.2.) Patients with a negative or equivocal overall result (FISH test ratio of <2.2, < 6.0 HER2 gene copies per nucleus) and staining scores of 0, 1+, 2+ or 3+ (in 30% or less neoplastic cells) by IHC are not eligible for participation in the trial. Equivocal local results from non certified laboratories may be submitted for a final determination by the certified laboratory. ErbB2 status must be tested in local or regional certified laboratories prior to randomisation. If local FISH test is performed in non-certified laboratories, the PathVysion test (Vysis) or the INFORM HER2/neu test (Ventana Inc.) must be used, but will also need confirmation of the results by a certified laboratory. IHC overexpression scores obtained locally will also need confirmation in a certified laboratory to be considered as an entry criteria. Patients with negative local FISH/CISH tests (test ratio of < 1.8, < 4.0 ErbB2 gene copies per nucleus) or 0 and 1+ scores by IHC are not eligible for participation in the trial. Positive local FISH tests (>6 ErbB2 gene copies per nucleus, or a FISH ratio of more than 2.2) or 2/3+ overexpression by IHC obtained at non-certified local laboratories must be confirmed by some of the certified laboratories before randomisation; 6) Hormone receptor (HR) status: - Oestrogen Receptor (ER) status must be known. 7) Haematopoietic status: - Absolute neutrophil count > 1,5 x 10^9/L, - Platelet count > 100 x 10^9/L, - Hemoglobin at least 9 g/dl, 8) Hepatic status: - Bilirubin <= 2 x upper limit of normal (ULN), - AST and ALT <= 2.5 times ULN, - Alkaline phosphatase <= 2.5 times ULN, 9) Renal status: - Creatinine <= 2.0 mg/dL, 10) Cardiovascular: - Baseline LVEF >= 50% measured by echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan, 11) Negative serum pregnancy test, within 2-weeks (preferably 7 days) prior to randomization (For women of childbearing potential) 12) Fertile patients must use effective contraception (barrier method - condoms, diaphragm - also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed) 13) Signed informed consent form (ICF) 14) Patient accepts to make available tumour samples for submission to central laboratory to conduct translational studies as part of this protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
Exclusion criteria:
1) Received any prior treatment for primary invasive breast cancer; 2) History of other malignancy. However, subjects with a past or current history of completely resected basal and squamous cell carcinoma of the skin or successfully treated in situ carcinoma of the cervix are eligible; 3) Diagnosis of inflammatory breast cancer; 4) Bilateral cancer; 5) Multi-focal cancer; 6) Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, uncontrolled hypertension (>=180/110), unstable diabetes mellitus, dyspnoea at rest, or chronic therapy with oxygen; 7) Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject?s safety; 8) Unresolved or unstable, serious adverse events from prior administration of another investigational drug; 9) Active or uncontrolled infection; 10) Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF; 11) Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded; 12) Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy other than the trial therapies); 13) Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial; 14) Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trastuzumab or lapatinib or their excipients; 15) Pregnant or lactating women; 16) Concomitant use of CYP3A4 inhibitors or inducers (see Section 7.2 for list of prohibited medications).
Age minimum:
Age maximum:
Gender:
Female: yes
Male: no
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Health Condition(s) or Problem(s) studied
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Women with primary ErbB2 overexpressing and/or gene amplified breast cancer >2cm diameter who have not undergone previous treatment for invasive breast cancer.
MedDRA version: 9.1
Level: LLT
Classification code 10057654
Term: Breast cancer female
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Intervention(s)
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Product Name: Lapatinib
Product Code: GW572016
Pharmaceutical Form: Capsule, hard
CAS Number: 388082-78-8
Current Sponsor code: GW572016
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Trade Name: HERCEPTIN*EV 1FL 150MG
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: Trastuzumab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Product Name: Paclitaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Paclitaxel
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-
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Primary Outcome(s)
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Secondary Objective: To compare the following criteria between the three treatment arms: Safety and efficacy (objective response rate); percent of patients with node-negative disease at surgery; rate of conversion to breast conserving surgery and to breast surgery of patients with non-operable breast cancer; disease free (DFS) and overall survival (OS)). - To identify the molecular characteristics of responding tumours; - To study biomarkers expression and establish correlations with clinical outcome; - To establish associations between PET/CT, tumour response and molecular changes and between circulating tumour cell (CTC) changes and tumour molecular changes; - To hypothesize about predictive value of early PET/CT imaging and predictive value of CTCs for evaluation of response to targeted anti-ErbB2 therapies; - to prospectively study the effect of targeted treatments on CTCs and the prognostic/predictive value of monitoring CTCs in patients with breast cancer.
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Main Objective: - To evaluate and compare the rate of pCR at the time of surgery in patients with HER2/ErbB2 overexpressing or amplified operable breast cancer randomised to lapatinib followed by lapatinib plus paclitaxel versus trastuzumab followed by trastuzumab plus paclitaxel versus lapatinib in combination with trastuzumab followed by lapatinib, trastuzumab plus paclitaxel
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Primary end point(s): Pathological complete response (pCR) at time of surgery.
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Secondary ID(s)
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EGF106903
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2006-000564-81-FR
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Source(s) of Monetary Support
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Ethics review
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Status: Approved
Approval date: 06/12/2007
Contact:
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