E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced/inflammatory or large operable brest cancer. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
The primary objective of the phase II is to assess the activity of the combination docetaxel + anti-HER2 treatment (lapatinib or lapatinib+trastuzumab) followed by FEC. The pathological response rate will be used as a surrogate for activity. The reference arm will be docetaxel+trastuzumab (3 cycles) followed by FEC 100 (3 cycles). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of the Phase II stage are: * To assess tolerability * To assess clinical activity. * To identify genes that may predict response to lapatinib + docetaxel combination |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Breast cancer population for Phase II part * Female patients with any large operable T2 or T3 breast cancers, M0 * Or female patients with locally advanced or inflammatory breast cancer defined as: - Clinical T4 a,b,c,d, any N (inflammatory breast carcinoma: tumor mass, breast enlargement, oedema and warmth of the skin are often present but not mandatory for the diagnosis) - any clinical T, N2 or N3 (ipsilateral supraclavicular nodes) - And M0 * Presence of bilateral breast cancer, provided only 1 side is HER2 positive * Histologically confirmed diagnosis of invasive breast cancer * Known hormone receptor status: ER/PR positive or negative. * HER-2 positive (IHC 3+, or IHC 2+ and FISH/CISH +, or FISH, or CISH+ only) * Two frozen trucuts with a 14 G needle are mandatory for every core biopsy indicated by the translational research study * Age 18 to 70 years * WHO performance status 0-2 * Adequate bone marrow function: hemoglobin > 10.0 g/dl or 6.2 mmol/L, neutrophils > 1.5 x 10exp9/L and platelets > 100 x 10exp9/L * Adequate hepatic and renal function, defined as follows: - Bilirubin < 1.5 x ULN, - AST and/or ALT < 3 x ULN - Serum creatinine < 1.5 x ULN * Patients must be accessible for repeat dosing and follow-up * Clinically normal cardiac function (LVEF assessed by MUGA or ECHO), normal 12 lead ECG, and in the past 6 months no serious cardiac illness or medical condition including but not confined to: - History of documented congestive heart failure (CHF) - High-risk uncontrolled arrhythmias - Angina pectoris requiring antianginal medication - Clinically significant valvular heart disease - Evidence of transmural infarction on ECG - Poorly controlled hypertension (e.g. systolic >180mm Hg or diastolic greater than 100mm Hg) * Drugs and several HERBAL CONSTITUENTS (e.g. bergamottin and glabridin), which are inducers or inhibitors of CYP3A4 must not be taken within 10 days prior to initiation of treatment and are prohibited while the patient is being treated with lapatinib (a detailed list is provided in chapter 5 of the protocol) * Women should either not be of childbearing potential (having had a hysterectomy, a bilateral oophorectomy or bilateral tubal ligation, or be post-menopausal with a total cessation of menses of > 1 year), or not be pregnant (negative serum pregnancy test at entry); should not be lactating; should agree to use contraceptive methods (with a documented failure rate < 1%, vasectomized partner sterile prior to trial entry and sole sexual partner or double-barrier contraception) from 2 weeks before your first study treatment until 4 weeks after your final study treatment. * Patients able to swallow and retain oral medication * Patients may not receive any non-protocol anticancer therapy, or other investigational agents while on study * Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial * Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. |
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E.4 | Principal exclusion criteria |
Exclusion criteria for Phase II part: * Prior history of malignancies except: - basal cell or squamous cell carcinoma of the skin - carcinoma in situ of the cervix - the patient has been free of any other malignancies for > 3 years. * Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones or stable chronic liver disease not requiring therapy as per investigator assessment) * Clinical signs of CNS involvement * Patients with active or uncontrolled infections or with serious illnesses, malabsorption syndrome or medical conditions, including patients with a history of chronic alcohol abuse, hepatitis, HIV and/or cirrhosis |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase II Primary endpoint: Pathological complete response rate defined as: “complete disappearance of invasive cancer with the exception of very few scattered tumour cells”. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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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End of study occurs when all of the following criteria have been satisfied: 1. Thirty days after all patients have stopped protocol treatment 2. The trial is mature for the analysis of the primary endpoint as defined in the protocol 3. The database has been fully cleaned and frozen for this analysis |
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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 | 3 |
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 | 7 |
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 |