Last updated: 11/07/2018 16:25:06
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.

Neo ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) StudyNeo ALTTO

GSK study ID
EGF106903
See study documents
Clinicaltrials.gov ID
NCT00553358
EudraCT ID
2006-000564-81
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: Neo ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) Study: A randomised, multicenter open-label phase III study of neoadjuvant lapatinib, trastuzumab and their combination plus paclitaxel in women with HER2/ErbB2 positive primary breast cancer
Trial description: This is a randomised, open label multicenter Phase III study comparing the efficacy of neoadjuvant lapatinib plus paclitaxel, versus trastuzumab plus paclitaxel, versus concomitant lapatinib and trastuzumab plus paclitaxel given as neoadjuvant treatment in HER2/ErbB2 over-expressing and/or amplified primary breast cancer.
Patients will be randomised to receive either: lapatinib 1500 mg daily, trastuzumab 4 mg/kg intravenous (IV) load followed by 2 mg/kg IV weekly, or lapatinib 1000 mg daily with trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for a total of 6 weeks. After this biological window, patients on monotherapy arms will continue on the same targeted therapy plus weekly paclitaxel 80 mg/m^2 for a further 12 weeks, up to definitive surgery. In the combination arm, patients will receive lapatinib 750 mg daily in combination with trastuzumab 2 mg/kg IV plus weekly paclitaxel 80mg/m^2 IV for a further 12 weeks, up to definitive surgery. After surgery, patients will receive three courses of adjuvant chemotherapy with 5-Fluorouracil Epirubicin Cyclophosphamide (FEC) followed by the same targeted therapy as in the biological window of the neoadjuvant setting for a further 34 weeks (in the combination arm, lapatinib dose will be 1000 mg daily in combination with trastuzumab). The planned total duration of the anti-HER2 therapy will be one year.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:

Number of participants with pathological complete response (pCR) at the time of surgery

Timeframe: Weeks 20 to 22

Secondary outcomes:

Number of participants with metabolic response of complete response (mCR), partial response (mPR), or stable disease (mSD) as determined by positron emission tomography/computed tomography (PET/CT)

Timeframe: Baseline, Week 2, and Week 6

Number of circulating tumor cells (CTC) in the bloodstream

Timeframe: Baseline, Week 2 of neo-adjuvant phase (Weeks 1-34), at surgery (Weeks 20 to 22), Week 10 of adjuvant phase, 6 months after completion of adjuvant treatment, and at recurrence

Estimate of treatment contrast for change from baseline in tumor size at Week 6 and at surgery

Timeframe: Week 6 and surgery (Weeks 20 to 22)

Percentage of participants event free at 3.0 years

Timeframe: Year 3

Number of participants with overall response at the time of surgery

Timeframe: Time of surgery (Weeks 20 to 22)

Number of participants with negative lymph nodes at the time of surgery

Timeframe: Time of surgery (Weeks 20 to 22)

Number of participants with overall response at Week 6

Timeframe: Week 6

Number of participants with actual indicated surgery

Timeframe: At surgery (Weeks 20 to 22)

Overall survival

Timeframe: From randomization until a median follow-up of approximately 4 years, then every 2.5 years until Year 10

Number of participants who died

Timeframe: From randomization until a median follow-up of 3.84 years

Number of participants with the indicated biomarker expression

Timeframe: Baseline, Week 2, and at surgery (Weeks 20 to 22)

Number of participants starting paclitaxel before completing 6 weeks of treatment with either lapatinib or trastuzumab

Timeframe: Week 6

Percentage of participants alive at 3.0 years

Timeframe: Year 3

Event-free survival (EFS)

Timeframe: Following randomization, at a median follow-up of approximately 4 years, then every 2.5 years until Year 10

Number of participants with an EFS event

Timeframe: Following randomization until a median follow-up of approximately 3.77 years

Interventions:
  • Drug: Paclitaxel
  • Vaccine: Trastuzumab
  • Drug: Lapatinib
    • Enrollment:
    455
    Primary completion date:
    2010-27-05
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Baselga J, Piccart M, Gelber R, di CosimoS, Viale G, Koehler M, Rojo F. Neo-ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) study BIG 1-06 /solti/EGF106903: a phase III translational study for HER2-overexpressing early breast cancer. Lancet. 2012;S140-6736(11):
    G. Gebhart, C. Gámez, E. Holmes, J. Robles, C. Garcia, M. Cortés, M. Bavington, E. de Azambuja, K. Fauria, V. Van Dooren, G. Aktan, M. Coccia-Portugal, S. Kim, P. Vuylsteke, H. Cure, H. Eidtmann, J. Baselga, M. Piccart, P. Flamen and S. Di Cosimo. FDG-PET/CT for Early Prediction of Response to Neoadjuvant Lapatinib, Trastuzumab, and their Combination in HER2-Positive Breast Cancer: Results from Neo-ALTTO . J Nucl Med. 2013;54(11):1862-8.
    H Azim, D Agbor-tarh, I Bradbury, P Dinh, J Baselega, I Smith, C Jackisch, S-B Kim, S Kuemmel, C-S Huang, P Vuylsteke, R Kuen Hsieh, L Dreosti, H Eidtmann, M Piccart, E de Azambuja, James Greger, SOLTI. Pattern of rash, diarrhea, and hepatic toxicities secondary to lapatinib and their association with age and response to neoadjuvant therapy. Analysis from the NeoALTTO trial. J Clin Oncol. 2013;31(36):4504-11.
    H. A. Azim Jr, F. Rothé , C. Aura, M. Bavi, M. Maetens, G. Gebhart C. Gamez, H. Eidtmann, J. Baselga, M. Piccart-Gebhart, P. Vuylsteke . Cure, J. Domont, A. Ferro, J. C. Toral Pena, E. de Azambuja etal. Circulating tumor cells, FDG-PET/CT and pathological complete response in HER2-positive breast cancer: a sub-study from the NeoALTTO trial. Breast J. 2013;22(6):1060-5.
    Medical condition
    Neoplasms, Breast
    Product
    lapatinib
    Collaborators
    Breast International Group, SOLTI, N/A
    Study date(s)
    January 2008 to August 2021
    Type
    Interventional
    Phase
    3

    Participation criteria

    Sex
    Female
    Age
    18+ years
    Accepts healthy volunteers
    none
    • Female gender;
    • Age ≥18 years;
    • Received any prior treatment for primary invasive breast cancer;
    • Previous (less than 10 years) or current history of malignant neoplasms, except for curatively treated:
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Female gender;
    • Age ≥18 years;
    • Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1
    • Histologically confirmed invasive breast cancer:
    • Primary tumour greater than 2 cm diameter, measured by clinical examination and mammography or echography,
    • Any N,
    • No evidence of metastasis (M0) (isolated supraclavicular node involvement allowed);
    • Over expression and/or amplification of HER2 in the invasive component of the primary tumour [Wolff et al 2006] and confirmed by a certified laboratory prior to randomisation
    • Known hormone receptor status.
    • Haematopoietic status:
    • Absolute neutrophil count ≥ 1,5 x 10^9/L,
    • Platelet count ≥ 100 x 10^9/L,
    • Hemoglobin at least 9 g/dl,
    • Hepatic status:
    • Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN). In the case of known Gilbert’s syndrome, a higher serum total bilirubin (< 2 x ULN) is allowed,
    • Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times ULN,
    • Alkaline phosphatase ≤ 2.5 times ULN,
    • Renal status:
    • Creatinine ≤ 2.0 mg/dL,
    • Cardiovascular:
    • Baseline left ventricular ejection fraction (LVEF) ³ 50% measured by echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan,
    • Negative serum pregnancy test, within 2-weeks (preferably 7 days) prior to randomization (For women of childbearing potential)
    • Fertile patients must use effective contraception (barrier method
    • condoms, diaphragm
    • also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed)
    • Signed informed consent form (ICF)
    • Patient accepts to make available tumour samples for submission to central laboratory to conduct translational studies as part of this protocol
    Exclusion criteria:
    • Received any prior treatment for primary invasive breast cancer; -Previous (less than 10 years) or current history of malignant neoplasms, except for curatively treated: – Basal and squamous cell carcinoma of the skin; – Carcinoma in situ of the cervix.
    • Patients with a prior malignancy diagnosed more than 10 years prior to randomisation may enter the study. Patients must have been curatively treated with surgery alone. Radiation therapy or systemic therapy (chemotherapy or endocrine) are NOT permitted. Prior diagnoses of breast cancer or melanoma are excluded.
    • Diagnosis of inflammatory breast cancer;
    • Bilateral cancer;
    • This criterion has been deleted from the protocol Version 1. Patients with multi-focal cancer are no longer excluded.
    • Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnoea at rest, or chronic therapy with oxygen;
    • 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;
    • Unresolved or unstable, serious adverse events from prior administration of another investigational drug;
    • Active or uncontrolled infection;
    • Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF;
    • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded;
    • Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy other than the trial therapies);
    • Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial;
    • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trastuzumab or lapatinib or their excipients;
    • Pregnant or lactating women;
    • Concomitant use of CYP3A4 inhibitors or inducers

    Trial location(s)

    This study does not involve prospective enrollment of participants.

    Study documents

    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Refer to study documents

    Recruitment status
    No longer a GSK study
    Actual primary completion date
    2010-27-05
    Actual study completion date
    Not applicable

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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