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AzTrials

Neoplasms, BreastPhase 3Neo ALTTONCT00553358

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

A Phase 3 study testing Lapatinib, Trastuzumab and Paclitaxel in people with Neoplasms, Breast, run by Novartis Pharmaceuticals at 121 sites in 24 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Neoplasms, Breast
What is being tested?
Lapatinib, Trastuzumab and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
455 participants
Where
121 sitesin 24 countries
Study dates
5 Jan 2008to 23 Dec 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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,
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  • 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

Who cannot join

  • 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;
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  • 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 locations and contacts

121 sites in 24 countries.

121 sites in 24 countries

Germany18 sites

  • Novartis Investigative Site

    Berlin, 13125

  • Novartis Investigative Site

    Berlin, 13589

  • Novartis Investigative Site

    Celle, Lower Saxony, 29223

  • Novartis Investigative Site

    Cologne, North Rhine-Westphalia, 50937

  • Novartis Investigative Site

    Dortmund, North Rhine-Westphalia, 44137

  • Novartis Investigative Site

    Essen, North Rhine-Westphalia, 45122

  • Novartis Investigative Site

    Frankfurt am Main, Hesse, 60590

  • Novartis Investigative Site

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

  • Novartis Investigative Site

    Fürstenwalde, Brandenburg, 15517

  • Novartis Investigative Site

    Fürth, Bavaria, 90766

  • Novartis Investigative Site

    Halle, Saxony-Anhalt, 06120

  • Novartis Investigative Site

    Hanover, Lower Saxony, 30625

  • Novartis Investigative Site

    Karlsruhe, Baden-Wurttemberg, 76135

  • Novartis Investigative Site

    Kiel, Schleswig-Holstein, 24105

  • Novartis Investigative Site

    Nuremberg, Bavaria, 90340

  • Novartis Investigative Site

    Rostock, Mecklenburg-Vorpommern, 18059

  • Novartis Investigative Site

    Stralsund, Mecklenburg-Vorpommern, 18435

  • Novartis Investigative Site

    Witten, North Rhine-Westphalia, 58452

Other trials in Germany

Spain11 sites

  • Novartis Investigative Site

    Barcelona, 08035

  • Novartis Investigative Site

    Girona, 17007

  • Novartis Investigative Site

    Lleida, 25198

  • Novartis Investigative Site

    Madrid, 28033

  • Novartis Investigative Site

    Madrid, 28041

  • Novartis Investigative Site

    Mataró, 08304

  • Novartis Investigative Site

    Santiago de Compostela, 15706

  • Novartis Investigative Site

    Seville, 41013

  • Novartis Investigative Site

    Toledo, 45004

  • Novartis Investigative Site

    Torrevieja (Alicante), 03186

  • Novartis Investigative Site

    Valencia, 46014

Other trials in Spain

France10 sites

  • Novartis Investigative Site

    Bayonne, 64100

  • Novartis Investigative Site

    Bordeaux, 33077

  • Novartis Investigative Site

    Le Mans, 72015

  • Novartis Investigative Site

    Levallois-Perret, 92300

  • Novartis Investigative Site

    Paris, 75010

  • Novartis Investigative Site

    Reims, 51100

  • Novartis Investigative Site

    Strasbourg, 67000

  • Novartis Investigative Site

    Strasbourg, 67085

  • Novartis Investigative Site

    Toulouse, 31076

  • Novartis Investigative Site

    Villejuif, 94805

Other trials in France

Ukraine9 sites

  • Novartis Investigative Site

    Chernivtsi, 58013

  • Novartis Investigative Site

    Dnipropetrovsk, 49100

  • Novartis Investigative Site

    Kharkiv, 61070

  • Novartis Investigative Site

    Kiev, 03115

  • Novartis Investigative Site

    Kryvyi Rih, 50048

  • Novartis Investigative Site

    Kyiv, 03022

  • Novartis Investigative Site

    Lviv, 79031

  • Novartis Investigative Site

    Odesa, 65055

  • Novartis Investigative Site

    Simferopol, 95023

Other trials in Ukraine

Italy8 sites

  • Novartis Investigative Site

    Genoa, Liguria, 16132

  • Novartis Investigative Site

    Lecco, Lombardy, 23900

  • Novartis Investigative Site

    Milan, Lombardy, 20132

  • Novartis Investigative Site

    Milan, Lombardy, 20141

  • Novartis Investigative Site

    Monza, Lombardy, 20052

  • Novartis Investigative Site

    Rome, Lazio, 00144

  • Novartis Investigative Site

    Sondrio, Lombardy, 23100

  • Novartis Investigative Site

    Trento, Trentino-Alto Adige, 38100

Other trials in Italy

Argentina7 sites

  • Novartis Investigative Site

    Berazategui, Buenos Aires, B1880BBF

  • Novartis Investigative Site

    Ciudad Autonoma de Buenos Aires, Buenos Aires, C1125ABD

  • Novartis Investigative Site

    Ciudad Autonoma de Buenos Aires, Buenos Aires, C1185AAT

  • Novartis Investigative Site

    Quilmes, 1878

  • Novartis Investigative Site

    Rosario, Santa Fe Province, S2000KZE

  • Novartis Investigative Site

    San Miguel de Tucumán, 4000

  • Novartis Investigative Site

    Santa Fe, 3000

Other trials in Argentina

India7 sites

  • Novartis Investigative Site

    Bangalore, 560029

  • Novartis Investigative Site

    Hyderabad, 500082

  • Novartis Investigative Site

    Mumbai, 400012

  • Novartis Investigative Site

    Nagpur, 440010

  • Novartis Investigative Site

    New Delhi, 110060

  • Novartis Investigative Site

    New Delhi, 110076

  • Novartis Investigative Site

    Pune, 411001

Other trials in India

Belgium6 sites

  • Novartis Investigative Site

    Brussels, 1000

  • Novartis Investigative Site

    Brussels, 1070

  • Novartis Investigative Site

    Brussels, 1090

  • Novartis Investigative Site

    Ghent, 9000

  • Novartis Investigative Site

    Leuven, 3000

  • Novartis Investigative Site

    Namur, 5000

Other trials in Belgium

South Korea5 sites

  • Novartis Investigative Site

    Seoul, 003722

  • Novartis Investigative Site

    Seoul, 06351

  • Novartis Investigative Site

    Seoul, 135-710

  • Novartis Investigative Site

    Seoul, 138-736

  • Novartis Investigative Site

    Songpa-gu, Seoul, 138-736

Other trials in South Korea

Taiwan5 sites

  • Novartis Investigative Site

    Changhua, 500

  • Novartis Investigative Site

    Tainan, 704

  • Novartis Investigative Site

    Taipei, 100

  • Novartis Investigative Site

    Taipei, 104

  • Novartis Investigative Site

    Taipei, 112

Other trials in Taiwan

United Kingdom5 sites

  • Novartis Investigative Site

    Bournemouth, BH7 7DW

  • Novartis Investigative Site

    Epping, Essex, CM16 6TN

  • Novartis Investigative Site

    London, EC1A 7BE

  • Novartis Investigative Site

    London, SE1 9RT

  • Novartis Investigative Site

    Nottingham, NG5 1PB

Other trials in United Kingdom

Brazil4 sites

  • Novartis Investigative Site

    Porto Alegre, Rio Grande do Sul, 90430-090

  • Novartis Investigative Site

    Porto Alegre, Rio Grande do Sul, 90560-030

  • Novartis Investigative Site

    Santo André, São Paulo, 09060-650

  • Novartis Investigative Site

    São Paulo, São Paulo, 03102-002

Other trials in Brazil

Russia4 sites

  • Novartis Investigative Site

    Moscow, 115 478

  • Novartis Investigative Site

    Ryazan, 390011

  • Novartis Investigative Site

    Saint Petersburg, 197022

  • Novartis Investigative Site

    Saint Petersburg, 197758

Other trials in Russia

South Africa4 sites

  • Novartis Investigative Site

    Athlone Park, Amanzimtoti, 4126

  • Novartis Investigative Site

    Capital Park, 0002

  • Novartis Investigative Site

    Parktown, 2193

  • Novartis Investigative Site

    Pretoria, Gauteng, 0181

Other trials in South Africa

Czechia3 sites

  • Novartis Investigative Site

    Brno, 656 53

  • Novartis Investigative Site

    Nový Jičín, 741 01

  • Novartis Investigative Site

    Prague, 100 34

Other trials in Czechia

Hong Kong3 sites

  • Novartis Investigative Site

    Hong Kong

  • Novartis Investigative Site

    Kowloon

  • Novartis Investigative Site

    Wan Chai

Other trials in Hong Kong

Romania3 sites

  • Novartis Investigative Site

    Bucharest, 022328

  • Novartis Investigative Site

    Bucharest, 050098

  • Novartis Investigative Site

    Cluj-Napoca, 400015

Other trials in Romania

Norway2 sites

  • Novartis Investigative Site

    Oslo, 0310

  • Novartis Investigative Site

    Oslo, 0407

Other trials in Norway

Peru2 sites

  • Novartis Investigative Site

    Lima, Lima 11

  • Novartis Investigative Site

    Lima, Lima 34

Other trials in Peru

Canada1 site

  • Novartis Investigative Site

    Montreal, Quebec, H4J 1C5

Other trials in Canada

Hungary1 site

  • Novartis Investigative Site

    Budapest, H-1122

Other trials in Hungary

Lithuania1 site

  • Novartis Investigative Site

    Vilnius, LT-08660

Other trials in Lithuania

Pakistan1 site

  • Novartis Investigative Site

    Karachi, 74800

Other trials in Pakistan

Sweden1 site

  • Novartis Investigative Site

    Gothenburg, SE-413 45

Other trials in Sweden

About this study

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

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 one year.

Primary objective is to evaluate and compare the rate of pathological complete response (pCR) at the time of surgery in patients with HER2/ErbB2 overexpressing or amplified operable breast cancer randomised to lapatinib followed by lapatinib plus paclitaxel versus trastuzumab followed by trastuzumab plus paclitaxel versus lapatinib in combination with trastuzumab followed by lapatinib, trastuzumab plus paclitaxel.

Read the detailed description

This was a parallel group, three-arm, randomized, multicenter, open-label phase III study. The study compared the efficacy and tolerability of neoadjuvant lapatinib and paclitaxel, versus trastuzumab and paclitaxel, versus the combination of lapatinib with trastuzumab and paclitaxel given as neoadjuvant treatment in HER2/ErbB2 over-expressing and/or amplified primary breast cancer. Subjects were randomized to receive lapatinib, trastuzumab or lapatinib plus trastuzumab for a total of 6 weeks. After this biological window, subjects continued on the same targeted therapy plus weekly paclitaxel for a further 12 weeks, until definitive surgery (total neoadjuvant therapy duration of 18 weeks). Paclitaxel could be initiated at Week 4 if there is evidence of progressive disease (PD) at that time. Within 6 weeks after surgery, subjects received 3 cycles of adjuvant 5-flourouracil, epirubicin and cyclophosphamide (FEC) followed by the same targeted therapy as in the biological window of the neoadjuvant phase for a further 34 weeks (to complete 52 weeks of anti-HER2 therapy).

After completing 52 weeks of (neo-)/adjuvant anti-HER2 therapy, subjects were scheduled to attend post-treatment follow-up every 3 months during the first year (months 12, 15, 18, 21, and 24), every 6months in Years 3 to 5 inclusive, and annually thereafter up to Year 10. Each subject was to be followed for 10 Years. All subjects were to be followed for EFS and OS up to 10 years from last subject randomized.

Being tested
Lapatinib, Trastuzumab, Paclitaxel
Keywords
Lapatinib, ErbB2+, Early Breast Cancer, Neoadjuvant, breast carcinoma, breast cancer, breast lump, HER2 positive metastatic breast cancer, breast cancer positive for human epidermal growth factor receptor 2 (HER2) HER2 positive metastatic breast cancer, breast cancer progression, estrogen-receptor (ER) positive(+) breast cancer, Paget's disease
Medical subject headings
Breast Neoplasms, Osteitis Deformans

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LapatinibDrug

    Small molecule receptor tyrosine kinase inhibitor

  • TrastuzumabBiological

    Therapeutic Monoclonal Antibody

  • PaclitaxelDrug

    antimicrotubule agent

Study groups in NCT00553358
Study groupRoleWhat they receive
Arm 1 LapatinibExperimental1500 mg lapatinib for 6 weeks followed by lapatinib plus weekly paclitaxel for an additional 12 weeks. After definitive surgery, 3 cycles of adjuvant FEC followed by 34 weeks of adjuvant lapatinib.
Receives: Drug: Lapatinib; Drug: Paclitaxel
Arm 2 TrastuzumabActive comparator4 mg/kg IV loading dose followed by 2 mg/kg IV weekly trastuzumab for 6 weeks followed by 2 mg/kg trastuzumab plus weekly paclitaxel for an additional 12 weeks. After definitive surgery, 3 cycles of adjuvant FEC followed by 34 weeks of adjuvant trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks).
Receives: Biological: Trastuzumab; Drug: Paclitaxel
Arm 3 Lapatinib plus TrastuzumabExperimental1000 mg lapatinib plus 4 mg/kg IV loading dose followed by 2 mg/kg IV weekly trastuzumab for 6 weeks, followed by 750 mg lapatinib plus 2 mg/kg IV weekly trastuzumab plus weekly paclitaxel for an additional 12 weeks. After definitive surgery, 3 cycles of adjuvant FEC followed by 34 weeks of adjuvant lapatinib (1000 mg) in combination with trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks).
Receives: Drug: Lapatinib; Biological: Trastuzumab; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Pathological Complete Response (pCR) at the Time of Surgery

    Pathological complete response is defined as no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. Surgical breast and axillary node resection specimens were evaluated for pathologic tumor response according to National Surgical Adjuvant Breast and Bowel Project (NSABP) guidelines, which do not take into account the histological nodal status.

    Measured: Weeks 20 to 22

Secondary outcomes (20)

  1. Number of Participants With Overall Response at Week 6

    The number of participants with overall response (complete response and/or partial response) was evaluated using World Health Organization (WHO) criteria by clinical examination and by mammography and breast echography with bi-dimensional measurements at Week 6. As per WHO criteria: complete response is defined as the disappearance of all lesions; partial response is defined as a greater than 50% decrease in the sum of products of the greatest length and width of the largest lesion; progressive disease is defined as a greater than 25% increase in the sum of products of all measurable lesions.

    Measured: Week 6

  2. Overall Response at the Time of Surgery

    The number of participants with overall response (complete response and/or partial response) was evaluated using WHO criteria by clinical examination and mammography and breast echography with bi-dimensional measurements at the time of surgery (Weeks 20 to 22). As per WHO criteria: complete response is defined as the disappearance of all lesions; partial response is defined as a greater than 50% decrease in the sum of products of the greatest length and width of the largest lesion; progressive disease is defined as a greater than 25% increase in the sum of products of all measurable lesions.

    Measured: Time of surgery (Weeks 20 to 22)

  3. Number of Participants With Negative Lymph Nodes at the Time of Surgery

    Participants were assessed for node-negative lymph nodes at the time of surgery. As per the pathological TNM (Tumor, Node, Metastases) classification (pTNM) of malignant tumors: pN, absence or presence and extent of regional lymph node metastasis. Node-negative (pN0) participants had no regional lymph node metastasis. Although not assessed in this measure, pT is the extent of primary tumor, and pM is the absence or presence of distant metastasis.

    Measured: Time of surgery (Weeks 20 to 22)

  4. Number of Participants With Actual Indicated Surgery

    Participants were assessed for the type of surgery they underwent for breast cancer. Non-conservative surgery is defined as a radical or modified radical mastectomy. Conservative surgery is comprised of a lumpectomy, a quadrantectomy/segmentectomy, or a partial mastectomy. Participants who were not assessed as being candidates for non-conservative or conservative surgery were classified as non-operable.

    Measured: At surgery (Weeks 20 to 22)

  5. Mean Change From Baseline in Tumor Size at Week 6 and at Surgery

    Mean change from baseline in tumor in tumor size. Change from baseline in tumor size was defined as tumor size at Week 6/ surgery (Weeks 20 to 22) minus tumor size at baseline. The difference in treatment arms was estimated for Lapatinib 1500 mg versus Trastuzumab 2 mg/kg and for Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg versus Trastuzumab 2 mg/kg.

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

  6. Number of Participants Starting Paclitaxel Before Completing 6 Weeks of Treatment With Either Lapatinib or Trastuzumab

    Participants with progressive disease at 4 week assessment that were permitted to commence treatment with paclitaxel.

    Measured: Week 6

  7. Event-free Survival (EFS) - Median Clinical Follow-up

    Event free survival (EFS) is defined as the time from randomization to first EFS event. For subjects who had breast cancer surgery, EFS events were post-surgery breast cancer relapse, second primary malignancy or death without recurrence. For subjects who did not have breast cancer surgery, EFS events were death during clinical follow-up or non-completion of any neoadjuvant investigational product due to disease progression.

    Measured: From randomization up to approximately year 10

  8. Event-free Survival (EFS) - Events and Censoring

    Event free survival (EFS) is defined as the time from randomization to first EFS event. For subjects who had breast cancer surgery, EFS events were post-surgery breast cancer relapse, second primary malignancy or death without recurrence. For subjects who did not have breast cancer surgery, EFS events were death during clinical follow-up or non-completion of any neoadjuvant investigational product due to disease progression.

    Measured: From randomization up to approximately year 10

  9. Overall Survival (OS) - Median Survival Follow-up

    Overall survival is defined as the period from randomization until death (from any cause). OS was assessed annually for up to 10 years after the randomization of the last participant into the study.

    Measured: From randomization up to approximately year 10

  10. Overall Survival (OS) - Deaths and Censoring

    Overall survival is defined as the period from randomization until death (from any cause). OS was assessed annually for up to 10 years after the randomization of the last participant into the study.

    Measured: From randomization up to approximately year 10

  11. Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population)

    The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis.

    Clinical follow-up is the period during which the patient is monitored such that all recurrence or second primary malignancy (SPM) or contralateral breast cancer (CBC) events would be reported. Patients are considered in clinical follow-up from randomisation until one of the following occurs: lost to follow-up, withdrawal of consent, end of follow-up due to completion of year 10 visit, termination of study follow-up, or death.

    Measured: up to year 10

  12. Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population)

    The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis.

    For patients who had breast cancer surgery, EFS events are post-surgery breast cancer relapse, second primary malignancy or death without recurrence. For patients who do not undergo breast cancer surgery, EFS events are death during clinical follow-up or non-completion of any neo-adjuvant investigational product due to disease progression or second primary malignancy or contralateral breast cancer.

    Measured: up to year 10

  13. Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population)

    The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis.

    Patients are considered in survival follow-up from randomisation until one of the following occurs: lost to follow-up, withdrawal of consent, end of follow-up due to completion of year 10 visit, termination of study follow-up, or death. For subjects with no death recorded in the database, time to death is censored.

    Measured: up to year 10

  14. Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population)

    The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis. Includes deaths due to any cause.

    Measured: up to year 10

  15. To Assess Safety Via a Comparison of the Three Treatment Arms - to Measure On-treatment Primary Cardiac Endpoints

    Measured: Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of 31 weeks.

  16. Metabolic Response Rate Determined by Positron Emission Tomography/Computed Tomography (PET/CT)

    Metabolic Response Rate determined by Positron Emission Tomography/Computed Tomography (PET/CT)

    Measured: Week 2 and Week 6

  17. Percentage of Participants With the Indicated Biomarker Expression - PIK3CA.

    Biomarker levels of phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) were assessed in participants at baseline.

    Measured: Baseline

  18. Percentage of Participants With the Indicated Biomarker Expression - PTEN.

    Biomarker levels of phosphate and tensin homolog deleted from chromosome 10 (PTEN) were assessed in participants at baseline.

    Measured: Baseline

  19. Ratio (95% CI) of Geometric Means in p95HER2 Expression in HR Positive Patients With pCR vs no pCR

    Ratio (95% CI) of geometric means in p95 human epidermal growth factor receptor (p95HER2) expression in hormone-receptor (HR) positive patients with pathological complete response (pCR) vs no pCR

    Measured: Baseline

  20. Percentage of Participants With Circulating Tumor Cells (CTC) in the Bloodstream

    Circulating tumor cells (CTCs) are cells that have detached from a primary tumor and circulate in the bloodstream. In the adjuvant phase, after surgery all participants received 3 courses of adjuvant 5-fluorouracil, epirubicin and cyclophosphamide, followed by lapatinib 1500 mg or trastuzumab 2 mg/kg or lapatinib 1000/750 mg plus trastuzumab 2 mg/kg given prior to surgery in the neoadjuvant setting for an additional 34 weeks.

    Measured: Measurement performed at one or more of the time points: baseline, week 2 or week 18

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2007 (estimated)
  2. Study start5 Jan 2008
  3. Primary completion27 May 2010
  4. Study completion23 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Masking
None (open label)
Enrolment
455 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00553358
Sponsor's protocol ID
EGF106903
Other IDs
2006-000564-81, CLAP016B2302
Acronym
Neo ALTTO
Status last verified
Aug 2021
First submitted
1 Nov 2007
Last updated
21 Sep 2021
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

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):

  • Rediti M, Venet D, Joaquin Garcia A, Maetens M, Vincent D, Majjaj S, El-Abed S, Di Cosimo S, Ueno T, Izquierdo M, Piccart M, Pusztai L, Loi S, Salgado R, Viale G, Rothe F, Sotiriou C. Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial. Nat Commun. 2024 Nov 29;15(1):10402. doi: 10.1038/s41467-024-54621-3.

    PubMed 39613746

  • Chumsri S, Li Z, Serie DJ, Norton N, Mashadi-Hossein A, Tenner K, Brauer HA, Warren S, Danaher P, Colon-Otero G, Partridge AH, Carey LA, Hilbers F, Van Dooren V, Holmes E, Di Cosimo S, Werner O, Huober JB, Dueck AC, Sotiriou C, Saura C, Moreno-Aspitia A, Knutson KL, Perez EA, Thompson EA. Adaptive immune signature in HER2-positive breast cancer in NCCTG (Alliance) N9831 and NeoALTTO trials. NPJ Breast Cancer. 2022 May 24;8(1):68. doi: 10.1038/s41523-022-00430-0.

    PubMed 35610260

  • Pizzamiglio S, Cosentino G, Ciniselli CM, De Cecco L, Cataldo A, Plantamura I, Triulzi T, El-Abed S, Wang Y, Bajji M, Nuciforo P, Huober J, Ellard SL, Rimm DL, Gombos A, Daidone MG, Verderio P, Tagliabue E, Di Cosimo S, Iorio MV. What if the future of HER2-positive breast cancer patients was written in miRNAs? An exploratory analysis from NeoALTTO study. Cancer Med. 2022 Jan;11(2):332-339. doi: 10.1002/cam4.4449. Epub 2021 Dec 17.

    PubMed 34921525

  • Powles RL, Redmond D, Sotiriou C, Loi S, Fumagalli D, Nuciforo P, Harbeck N, de Azambuja E, Sarp S, Di Cosimo S, Huober J, Baselga J, Piccart-Gebhart M, Elemento O, Pusztai L, Hatzis C. Association of T-Cell Receptor Repertoire Use With Response to Combined Trastuzumab-Lapatinib Treatment of HER2-Positive Breast Cancer: Secondary Analysis of the NeoALTTO Randomized Clinical Trial. JAMA Oncol. 2018 Nov 1;4(11):e181564. doi: 10.1001/jamaoncol.2018.1564. Epub 2018 Nov 8.

    PubMed 29902299

  • Fumagalli D, Venet D, Ignatiadis M, Azim HA Jr, Maetens M, Rothe F, Salgado R, Bradbury I, Pusztai L, Harbeck N, Gomez H, Chang TW, Coccia-Portugal MA, Di Cosimo S, de Azambuja E, de la Pena L, Nuciforo P, Brase JC, Huober J, Baselga J, Piccart M, Loi S, Sotiriou C. RNA Sequencing to Predict Response to Neoadjuvant Anti-HER2 Therapy: A Secondary Analysis of the NeoALTTO Randomized Clinical Trial. JAMA Oncol. 2017 Feb 1;3(2):227-234. doi: 10.1001/jamaoncol.2016.3824.

    PubMed 27684533

  • Salgado R, Denkert C, Campbell C, Savas P, Nuciforo P, Aura C, de Azambuja E, Eidtmann H, Ellis CE, Baselga J, Piccart-Gebhart MJ, Michiels S, Bradbury I, Sotiriou C, Loi S. Tumor-Infiltrating Lymphocytes and Associations With Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated With Lapatinib and Trastuzumab: A Secondary Analysis of the NeoALTTO Trial. JAMA Oncol. 2015 Jul;1(4):448-54. doi: 10.1001/jamaoncol.2015.0830.

    PubMed 26181252

  • Nuciforo PG, Aura C, Holmes E, Prudkin L, Jimenez J, Martinez P, Ameels H, de la Pena L, Ellis C, Eidtmann H, Piccart-Gebhart MJ, Scaltriti M, Baselga J. Benefit to neoadjuvant anti-human epidermal growth factor receptor 2 (HER2)-targeted therapies in HER2-positive primary breast cancer is independent of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) status. Ann Oncol. 2015 Jul;26(7):1494-500. doi: 10.1093/annonc/mdv175. Epub 2015 Apr 7.

    PubMed 25851628

  • de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. doi: 10.1016/S1470-2045(14)70320-1. Epub 2014 Aug 14.

    PubMed 25130998

  • Yarden Y, Pines G. The ERBB network: at last, cancer therapy meets systems biology. Nat Rev Cancer. 2012 Jul 12;12(8):553-63. doi: 10.1038/nrc3309.

    PubMed 22785351

  • Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gomez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horvath Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. doi: 10.1016/S0140-6736(11)61847-3. Epub 2012 Jan 17.

    PubMed 22257673

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lapatinib, Trastuzumab and Paclitaxel in people with Neoplasms, Breast, run by Novartis Pharmaceuticals at 121 sites in 24 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 121 sites in Germany, Spain, France, Ukraine, Italy and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Oct 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Pathological Complete Response (pCR) at the Time of Surgery (time frame: Weeks 20 to 22). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00553358, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2021.

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