E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Women with primary ErbB2 overexpressing and/or gene amplified breast cancer > 2 cm diameter who have not undergone previous treatment for invasive breast cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057654 |
E.1.2 | Term | Breast cancer female |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate and compare the rate of pathological complete response (pCR) at the time of surgery in patients with ErbB2 overexpressing or amplified operable breast cancer randomised between the study treatment arms. |
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E.2.2 | Secondary objectives of the trial |
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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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Female
2) Age ≥18 years
3) Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1
4) Histologically confirmed invasive breast cancer: - Primary tumour greater than 2 cm diameter, - Any Node, - No evidence of metastasis (M0) (isolated supraclavicular node involvement allowed)
5) Over expression and/or gene amplification of ErbB2 in the invasive component of the primary tumour according to one of the following definitions and confirmed by a certified laboratory prior to randomisation:
– 3+ over expression by IHC; – 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
Patients with a negative or equivocal overall result and staining scores of 0, 1+, 2+ or 3+ (in 30% or less neoplastic cells) by IHC are not eligible
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. Local testing performed in non-certified laboratories, will also need confirmation of the results by a certified laboratory.
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,
0) 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 as specified in the protocol
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 |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pathological complete response (pCR) at time of surgery. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 101 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 12 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 12 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |