A randomised, multicentre, open-label, phase III study of neoadjuvant lapatinib, trastuzumab, and their combination plus paclitaxel in women with HER2/ErbB2 positive primary breast cancer - NeoALTTO

• Register: EUCTR
• Last refreshed on: 11 March 2020
• Main ID: EUCTR2006-000564-81-FR
• Date of registration: 22/06/2007
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research and Development Limited
• Public title: A randomised, multicentre, open-label, phase III study of neoadjuvant lapatinib, trastuzumab, and their combination plus paclitaxel in women with HER2/ErbB2 positive primary breast cancer - NeoALTTO
• Scientific title: A randomised, multicentre, open-label, phase III study of neoadjuvant lapatinib, trastuzumab, and their combination plus paclitaxel in women with HER2/ErbB2 positive primary breast cancer - NeoALTTO
• Date of first enrolment: 14/01/2008
• Target sample size: 450
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-000564-81
• Study type: Interventional clinical trial of medicinal product
• Study design: 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Germany, Greece, Hungary, Italy, Lithuania, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

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
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:
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Women with primary ErbB2 overexpressing and/or gene amplified breast cancer > 2 cm diameter who have not undergone previous treatment for invasive breast cancer
MedDRA version: 9.1 Level: LLT Classification code 10057654 Term: Breast cancer female

Intervention(s)

Trade Name: Tyverb
Product Name: Lapatinib
Product Code: GW572016
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Lapatinib
CAS Number: 388082-78-8
Other descriptive name: lapatinib ditosylate monohydrate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Trade Name: Herceptin
Product Name: Trastuzumab
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Trastuzumab
CAS Number: 18022-69-1
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
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Primary Outcome(s)

Main Objective: 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.

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.

Primary end point(s): Pathological complete response (pCR) at time of surgery.

Secondary ID(s)

EGF106903

Ethics review

Status: Approved
Approval date: 14/01/2008
Contact: