ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) study. A randomised, multi-centre, open-label, phase III study of adjuvant lapatinib, trastuzumab, their sequence and their combination in patients with HER2/ErbB2 positive primary breast cancer. - ALTTO
- Conditions
- Operable primary breast cancer with over expression/ amplification of HER2.MedDRA version: 9.1Level: LLTClassification code 10006187Term: Breast cancer
- Registration Number
- EUCTR2006-000562-36-EE
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 8000
1. Age > or = 18 years;
2. Eastern Cooperative Oncology Group performance status < or = 1;
3. Non-metastatic operable primary invasive adenocarcinoma of the breast fulfilling the following:
a. Histologically confirmed;
b. Adequately excised (exceptions: patients who have 'non-resectable' deep margin invasion or histologically documented infiltration of the skin (pT4) are eligible provided they have had or will receive radiotherapy);
c. Axilla dissected; sentinel node sampling is allowed provided that axillary dissection follows confirmation of a positive sentinel node (sentinel node sampling alone is not acceptable after neo-adjuvant chemotherapy);
d. Axillary node positive patient or node negative patient with a tumor of more than 1 cm in greatest diameter (> or = T1c);
4. Known hormone receptor status (ER/PgR or ER alone);
5. For designs 1 and 2 must have received at least four cycles of an approved anthracycline-based (neo-) adjuvant chemotherapy regimen;
For design 1: Randomisation must be performed no longer than 12 weeks from day 1 of the last chemotherapy cycle.
For design 2: Randomisation must be performed no longer than 6 weeks from day 1 of the last anthracycline-containing chemotherapy cycle.
For design 2b: Randomisation must be performed no longer than 8 weeks from definitive surgery. Non-anthracycline platinum containing and study treatment should start concomitantly and no more than 14 days after randomization.
6. Baseline LVEF > or = 50% for design 1 and design 2 after completion of all anthracycline-based (neo-) adjuvant chemotherapy and prior to the targeted therapy(ies); for design 2b prior to targeted therapies and chemotherapy.
7. Confirmed overexpression and/or gene amplification of ErbB2 (HER2) in the invasive component of the primary tumour, according to one of the following definitions:
– 3+ overexpression by IHC (>30% of invasive tumour cells);
– 2+ or 3+ (in 30% or less neoplastic cells) overexpression by IHC and positive in situ hybridisation (FISH/CISH) test;
– ErbB2 (HER2) gene amplification by FISH/CISH;
- Patients with a negative or equivocal overall result for overexpression and/or gene amplification are not eligible for participation in the trial;
- Equivocal local results may be submitted for a final determination by the central laboratory.
8. Completion of all necessary baseline laboratory and radiological investigations;
9. Signed written informed consent prior to any study specific screening procedures.
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
Patients meeting any of the following criteria are not eligible for this study:
1. History of any prior (ipsi- and/or contralateral) invasive breast carcinoma;
2. Past or current history of malignant neoplasms, unless curatively treated;
3. Any clinically staged T4 tumour, including inflammatory breast cancer;
4. Bilateral tumours;
5. Multifocal tumor - this exclusion criterion has been removed as of protocol am 1
6. Maximum cumulative dose of doxorubicin >360mg/m2 or maximum cumulative dose of epirubicin >720mg/m2 or any prior anthracyclines unrelated to the present breast cancer;
7. Previous (neo-) adjuvant chemotherapy with peripheral stem cell or bone marrow stem cell support;
8. Any prior mediastinal irradiation except internal mammary node irradiation for the present breast cancer;
9. Patients with positive or suspicious internal mammary nodes identified by sentinel node technique which have not been irradiated or will not be irradiated, or patients with supraclavicular lymph node involvement;
10. Prior anti-ErbB2 (HER2) therapy for any reason, or other prior biologic or immunotherapy for breast cancer;
11. Concurrent anti-cancer treatment, except hormonal therapy;
12. Concurrent anti-cancer treatment in another investigational trial with hormone therapy or immunotherapy;
13. Serious cardiac illness or medical conditions including but not confined to:
– History of documented congestive heart failure (CHF) or systolic dysfunction (LVEF < 50%) ;
– High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV-block, supraventricular arrhythmias which are not adequately rate-controlled);
– 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 >100mm Hg);
14. Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness;
15. Any of the following abnormal laboratory tests immediately prior to randomisation:
– serum total bilirubin;
– alanine amino transferase (ALAT) or aspartate amino transferase (ASAT);
– alkaline phosphatase (ALP);
– serum creatinine;
– total white blood cell count (WBC);
– absolute neutrophil count;
– platelets;
16. Unresolved or unstable serious toxicity from prior adjuvant chemotherapy or radiotherapy;
17. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, or persons unable to swallow oral medication. Subjects with ulcerative colitis are also excluded;
18. Pregnant or lactating women (women of childbearing potential must have a negative pregnancy test - urine or serum - within 7 days prior to randomisation);
19. Women of childbearing potential including women whose last menstrual period was <1 year ago (unless surgically sterile) who are unable or unwilling to use adequate contraceptive measures during study treatment as defined in the protocol;
20. Concomitant use of CYP3A4 inhibitors or inducers.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method