AzTrials
AzTrials

Neoplasms, BreastPhase 2CHERLOBNCT00429299

Neoadjuvant Study With Chemotherapy, Lapatinib And Trastuzumab In Breast Cancer

A Phase 2 study testing lapatinib, trastuzumab and paclitaxel in people with Neoplasms, Breast, run by GlaxoSmithKline at 17 sites in 3 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

Evaluate the activity of Trastuzumab, Lapatinib, and a combination of both agents with chemotherapy in the preoperative (neoadjuvant) treatment of early breast cancer. Read more about this study

Who is it for?
Ages 18 to 65 years, 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
121 participants
Where
17 sitesin 3 countries
Study dates
Aug 2006to Jun 2012
Phase
Phase 2
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 to 65 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed infiltrating primary breast cancer of > 2.0 cm in largest clinical diameter
  • HER2 positive tumor (either IHC 3+ or FISH+)
  • Availability of tumor tissue suitable for biological and molecular examination before starting primary treatment
  • Age >18, < 65 years
  • ECOG PS 0-1
  • Normal organ and marrow function as defined below:
Show all 18Show fewer
  • leukocytes ³ 3000/microL
  • absolute neutrophil count ³ 1,500/microL
  • platelets ³ 100,000/microL
  • total bilirubin <= 1.5x ULN. In case of Gilbert's syndrome, <2 x ULN is allowed
  • AST (SGOT)/ALT(SGPT)<= 2.5 X institutional upper limit of normal
  • Alkaline phosphatase <= 2.5 x ULN
  • Creatinine within normal institutional limits
  • Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA scan
  • Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of lapatinib will be determined following review of their use by the Principal Investigator. A list of medications and substances known or with the potential to interact with CYP450 isoenzymes is provided
  • The effects of lapatinib on the developing human fetus at the recommended therapeutic dose are unknown; women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately, the patient should be apprised of the potential hazard to the fetus and potential risk for loss of the pregnancy
  • Ability to understand and the willingness to sign a written informed consent document
  • Ability to swallow and retain oral medication

Who cannot join

  • Stage IIIB, IIIC, and inflammatory breast cancer
  • Stage IV breast cancer
  • Contraindication to the treatment with anthracycline, paclitaxel and/or trastuzumab
  • Prior treatment with chemotherapy, endocrine therapy or radiotherapy. Prior treatment with EGFR targeting therapies
  • Treatment with any other investigational agents, or with all herbal (alternative) medicines
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib
Show all 12Show fewer
  • Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnancy or breastfeeding; (breast feeding should be discontinued to be enrolled in the study)
  • Women of childbearing potential that refusal to adopt adequate contraceptive measures
  • HIV-positive patients receiving combination anti-retroviral therapy
  • GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)
  • Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors

Trial locations and contacts

17 sites in 3 countries.

17 sites in 3 countries

Italy15 sites

  • GSK Investigational Site

    Brindisi, Apulia, 72100

  • GSK Investigational Site

    Candiolo (TO), Piedmont, 10060

  • GSK Investigational Site

    Carpi (MO), Emilia-Romagna, 41012

  • GSK Investigational Site

    Cremona, 26100

  • GSK Investigational Site

    Forlì, Emilia-Romagna, 47100

  • GSK Investigational Site

    Modena, Emilia-Romagna, 41100

  • GSK Investigational Site

    Parma, Emilia-Romagna, 43100

  • GSK Investigational Site

    Pavia, 27100

  • GSK Investigational Site

    Perugia, 06156

  • GSK Investigational Site

    Piacenza, Emilia-Romagna, 29100

  • GSK Investigational Site

    Pisa, Tuscany, 56126

  • GSK Investigational Site

    Reggio Emilia, 42100

  • GSK Investigational Site

    Rimini, Emilia-Romagna, 47900

  • GSK Investigational Site

    Treviglio (BG), Lombardy, 24047

  • GSK Investigational Site

    Varese, 21100

Other trials in Italy

Germany1 site

  • GSK Investigational Site

    Berlin, State of Berlin, 13125

Other trials in Germany

Poland1 site

  • GSK Investigational Site

    Warsaw, 00-909

Other trials in Poland

About this study

Official title: Chemotherapy Plus Lapatinib or Trastuzumab or Both in Her2+ Primary Breast Cancer. A Randomized Phase IIb Study With Biomarker Evaluation.

Evaluate the activity of Trastuzumab, Lapatinib, and a combination of both agents with chemotherapy in the preoperative (neoadjuvant) treatment of early breast cancer.

Being tested
lapatinib, trastuzumab, paclitaxel, fluorouracil, epidoxorubicin
Keywords
neo-adjuvant trastuzumab early breast cancer lapatinib
Medical subject headings
Breast Neoplasms

What participants receive

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

  • lapatinibDrug

    Also called Tyverb/Tykerb

    Arm B 1250mg/d PO Arm C 750mg/d PO

  • trastuzumabBiological

    Also called Herceptin

    First dose 4mg/kg in 60mins, then weekly 2mg/kg in 30 mins

  • paclitaxelDrug

    Also called Taxol

    80mg/sqm 1 hour infusion for 12 weeks

  • fluorouracilDrug

    600mg/sqm iv day 1 q21 days for four coursess

  • epidoxorubicinDrug

    75mg/sqm iv day 1 q21 days for four courses

  • cyclophosphamideDrug

    600mg/sqm day 1 q21 days for four courses

Study groups in NCT00429299
Study groupRoleWhat they receive
Arm AActive comparatorChemotherapy plus trastuzumab
Receives: Biological: trastuzumab; Drug: paclitaxel; Drug: fluorouracil; Drug: epidoxorubicin; Drug: cyclophosphamide
Arm BExperimentalChemotherapy plus lapatinib
Receives: Drug: lapatinib; Drug: paclitaxel; Drug: fluorouracil; Drug: epidoxorubicin; Drug: cyclophosphamide
Arm CActive comparatorChemotherapy plus trastuzumab plus lapatinib
Receives: Drug: lapatinib; Biological: trastuzumab; Drug: paclitaxel; Drug: fluorouracil; Drug: epidoxorubicin; Drug: cyclophosphamide

What is being measured

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

  1. Percentage of Participants With Pathological Complete Response (pCR) in the Breast and in the Lymph Nodes

    Pathological Complete Response (pCR) is defined by the complete absence of infiltrating tumor cells in the breast and in the lymph nodes. The pathological response in the breast was evaluated according to the criteria of Miller and Payne as follows: Grade 1, no change or some alteration to individual malignant cells, but no reduction in overall cellularity; Grade 2, a minor loss in tumor cells (up to 30%); Grade 3, between an estimated 30% and 90% reduction in tumor cells; Grade 4, marked disappearance of tumor cells, with only a small cluster or a dispersed cell remaining (more than 90% loss); Grade 5, no identifiable malignant cells. Ductal carcinoma in situ (DCIS) may be present. Grades were interpreted as follows: Grade 1-2=no response; Grade 3-4=partial response; Grade 5=complete response. pCR was defined by comparing specimens obtained at Baseline (biopsy) to those obtained upon surgery.

    Measured: At Baseline and surgery (within 5 weeks after the last chemotherapy administration) (assessed up to Study Week 29)

Secondary outcomes (7)

  1. Percentage of Participants With the Indicated Clinical Objective Response (Complete Response and Partial Response), Stable Disease, and Progressive Disease, as Assessed by Ultrasonography

    The clinical response was evaluated by comparing the tumor size (largest tumor diameter) before (at Baseline [biopsy]) and after treatment (before surgery), as assessed by ultrasonography examination. The clinical response was scored by Response Evaluation Criteria in Solid Tumors (RECIST) as follows: complete clinical response: the nodule is not detectable and all the ultrasound abnormality detected at diagnosis disappeared (margins circumscribed, round oval shape, parallel orientation, isoechoic echo pattern, no posterior acoustic features, echogenic lesion boundary, and tumor vascularity not present); partial clinical response: the longest diameter of the tumor has been reduced by >50%, and the ultrasound characteristics of the tumor persist; no response (stable disease): the longest diameter of the tumor has been reduced by <50% or has increased by no more than 20% from the starting value; progressive disease: tumor longest diameter has increased >20% from the starting value.

    Measured: At Baseline and after primary treatment (within 2 weeks before surgery; up to Study Week 27)

  2. Percentage of Participants Who Had Breast-conserving Surgery (BCS), Mastectomy, and Conversion From Mastectomy to BCS

    The percentage of participants who had BCS and mastectomy and who were initiallycandidates for mastectomy and who actually had BCS was measured. At Baseline, the surgeon stated, within 4 weeks before starting the primary treatment, which type of surgical treatment he would perform in the absence of primary therapy and in the case of primary therapy (if the tumor size was reduced by the primary treatment to less than 3 centimeters), and the reasons for these choices. The rules for choosing the type of surgical treatment are reported in the Consensus Conference on Primary Treatment of Early Breast Cancer. The surgeon was to have re-evaluated the participant after primary treatment. In cases in which the type of surgical procedure was different from that originally programmed, the reason for this chance was to have been reported.

    Measured: At Baseline and at surgery (up to Study Week 29)

  3. Time to Treatment Failure From the Start of Primary Therapy

    Time to treatment failure (TTF) is defined as the interval of time between the date of randomization and the earliest date of disease progression, premature treatment discontinuation and death due to any cause. The overall disease progression date is the earlier of the two disease progression dates from ultrasonography and mammography assessments. For ultrasonography, disease progression is defined as at least 20% increase in the longest diameter of the primary lesion at pre-surgery comparing to Baseline. For mammography, disease progression is defined as at least 20% increase in the larger nodule dimension at pre-surgery comparing to Baseline. For participants who has neither progressed, pre-maturely withdrawn or died, time to treatment failure will be censored at the latest date of ultrasonography and mammography tumor assessments.

    Measured: From randomization up to Study Week 307

  4. Number of Participants With Treatment Failure

    Treatment failure is defined as the occurrence of local tumor progression (including ipsilateral and controlateral breast), distant tumor progression, permanent treatment discontinuation (either for the experimental or conventional arm), or death due to any cause.

    Measured: From randomization up to 29 weeks

  5. Percentage of Inhibition of Biomarkers Ki67, pAKT, pMAPK, Tunel Test, PTEN, and pEGFR After Treatment

    The percentage of inhibition of intermediate (EGFR, HER2, pMAPK, pAKT, PTEN, and PI3KCA) and final (TUNEL and Ki67) biomarkers of the proliferation and apoptosis pathways was calculated as the difference between the staining scores before (Baseline [biopsy]) and after treatment (withdrawal).

    Measured: At Baseline and Withdrawal (assessed up to Study Week 29)

  6. Number of Participants With Any Adverse Event (AE), Including Serious Adverse Events (SAEs), Occurring in >=5% of Participants

    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment had been exercised in deciding whether reporting was appropriate in other situations.

    Measured: From the first dose of randomized therapy to 30 days after the last dose of randomized therapy (assessed up to Study Week 29)

  7. Number of Variations/Somatic Mutation in PI3KCA at Baseline

    Analysis of mutations in the PI3KCA gene was performed from RNA extracted from frozen tumor tissue samples (sections). A gene is either a wild-type (no mutation) or mutated (presence of a mutation). Exons 9 and 20 of the PI3KCA gene were accessed (high frequency mutation at these two spots).

    Measured: Baseline

Timeline

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

  1. First posted31 Jan 2007 (estimated)
  2. Study startAug 2006
  3. Primary completionJun 2012
  4. Study completionJun 2012

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
121 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00429299
Sponsor's protocol ID
EGF106988
Acronym
CHERLOB
Status last verified
Jan 2016
First submitted
29 Jan 2007
Last updated
22 Mar 2016
Data monitoring committee
No

Publications

  • Guarneri V, Frassoldati A, Bottini A, Cagossi K, Bisagni G, Sarti S, Ravaioli A, Cavanna L, Giardina G, Musolino A, Untch M, Orlando L, Artioli F, Boni C, Generali DG, Serra P, Bagnalasta M, Marini L, Piacentini F, D'Amico R, Conte P. Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study. J Clin Oncol. 2012 Jun 1;30(16):1989-95. doi: 10.1200/JCO.2011.39.0823. Epub 2012 Apr 9.

    PubMed 22493419

  • Guarneri V, Dieci MV, Griguolo G, Miglietta F, Girardi F, Bisagni G, Generali DG, Cagossi K, Sarti S, Frassoldati A, Gianni L, Cavanna L, Pinotti G, Musolino A, Piacentini F, Cinieri S, Prat A, Conte P; of the CHER-Lob study team. Trastuzumab-lapatinib as neoadjuvant therapy for HER2-positive early breast cancer: Survival analyses of the CHER-Lob trial. Eur J Cancer. 2021 Aug;153:133-141. doi: 10.1016/j.ejca.2021.05.018. Epub 2021 Jun 19.

    PubMed 34153715

  • Guarneri V, Dieci MV, Frassoldati A, Maiorana A, Ficarra G, Bettelli S, Tagliafico E, Bicciato S, Generali DG, Cagossi K, Bisagni G, Sarti S, Musolino A, Ellis C, Crescenzo R, Conte P. Prospective Biomarker Analysis of the Randomized CHER-LOB Study Evaluating the Dual Anti-HER2 Treatment With Trastuzumab and Lapatinib Plus Chemotherapy as Neoadjuvant Therapy for HER2-Positive Breast Cancer. Oncologist. 2015 Sep;20(9):1001-10. doi: 10.1634/theoncologist.2015-0138. Epub 2015 Aug 5.

    PubMed 26245675

  • Guarneri V, Generali DG, Frassoldati A, Artioli F, Boni C, Cavanna L, Tagliafico E, Maiorana A, Bottini A, Cagossi K, Bisagni G, Piacentini F, Ficarra G, Bettelli S, Roncaglia E, Nuzzo S, Swaby R, Ellis C, Holford C, Conte P. Double-blind, placebo-controlled, multicenter, randomized, phase IIb neoadjuvant study of letrozole-lapatinib in postmenopausal hormone receptor-positive, human epidermal growth factor receptor 2-negative, operable breast cancer. J Clin Oncol. 2014 Apr 1;32(10):1050-7. doi: 10.1200/JCO.2013.51.4737. Epub 2014 Mar 3.

    PubMed 24590635

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing lapatinib, trastuzumab and paclitaxel in people with Neoplasms, Breast, run by GlaxoSmithKline at 17 sites in 3 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 18 inclusion and 12 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 22 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Italy, Germany, Poland. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 22 Mar 2016). 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?

Percentage of Participants With Pathological Complete Response (pCR) in the Breast and in the Lymph Nodes (time frame: At Baseline and surgery (within 5 weeks after the last chemotherapy administration) (assessed up to Study Week 29)). 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 NCT00429299, which also lists 4 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 22 Mar 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in