A phase I-II study of lapatinib and docetaxel as neoadjuvant treatment for HER-2 positive locally advanced/inflammatory or large operable breast cancer. - Lapatax

• Conditions: ocally advanced/inflammatory or large operable brest cancer.; MedDRA version: 14.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2006-000864-94-SI
• Lead Sponsor: European Organisation for Research and Treatment of Cancer (EORTC)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-08-09
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 180

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.
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
F.1.3.1 Number of subjects for this age range

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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).;Secondary Objective: Secondary objectives of the Phase II stage are:<br>* To assess tolerability<br>* To assess clinical activity.<br>* To identify genes that may predict response to lapatinib + docetaxel combination;Primary end point(s): Phase II Primary endpoint:<br>Pathological complete response rate defined as: complete disappearance of invasive cancer with the exception of very few scattered tumour cells”.