Neoadjuvant Study With Chemotherapy, Lapatinib And Trastuzumab In Breast Cancer

NCT00429299 | Completed Phase 2 Results

• 1 other identifier: EGF106988
• Study Type: interventional
• Target: 121
• Locations: 3 countries
• Sites: 17

Brief Summary

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

Conditions

Neoplasms, Breast

Keywords

neo-adjuvant trastuzumab early breast cancer lapatinib

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (7)

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

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

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

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

• Time to Treatment Failure From the Start of Primary Therapy

  From randomization up to Study Week 307

• Number of Participants With Treatment Failure

  From randomization up to 29 weeks

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

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

Study Arms (3)

Arm A

ACTIVE COMPARATOR

Chemotherapy plus trastuzumab

Biological: trastuzumab; Drug: paclitaxel; Drug: fluorouracil; Drug: epidoxorubicin; Drug: cyclophosphamide

Arm B

EXPERIMENTAL

Chemotherapy plus lapatinib

Drug: lapatinib; Drug: paclitaxel; Drug: fluorouracil; Drug: epidoxorubicin; Drug: cyclophosphamide

Arm C

ACTIVE COMPARATOR

Chemotherapy plus trastuzumab plus lapatinib

Drug: lapatinib; Biological: trastuzumab; Drug: paclitaxel; Drug: fluorouracil; Drug: epidoxorubicin; Drug: cyclophosphamide

Interventions

lapatinib DRUG

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

Also known as: Tyverb/Tykerb

Arm B; Arm C

trastuzumab BIOLOGICAL

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

Also known as: Herceptin

Arm A; Arm C

paclitaxel DRUG

80mg/sqm 1 hour infusion for 12 weeks

Also known as: Taxol

Arm A; Arm B; Arm C

fluorouracil DRUG

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

Arm A; Arm B; Arm C

epidoxorubicin DRUG

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

Arm A; Arm B; Arm C

cyclophosphamide DRUG

600mg/sqm day 1 q21 days for four courses

Arm A; Arm B; Arm C

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (17)

GSK Investigational Site

Berlin, State of Berlin, 13125, Germany

Location

GSK Investigational Site

Brindisi, Apulia, 72100, Italy

Location

GSK Investigational Site

Carpi (MO), Emilia-Romagna, 41012, Italy

Location

GSK Investigational Site

Forlì, Emilia-Romagna, 47100, Italy

Location

GSK Investigational Site

Modena, Emilia-Romagna, 41100, Italy

Location

GSK Investigational Site

Parma, Emilia-Romagna, 43100, Italy

Location

GSK Investigational Site

Piacenza, Emilia-Romagna, 29100, Italy

Location

GSK Investigational Site

Rimini, Emilia-Romagna, 47900, Italy

Location

GSK Investigational Site

Treviglio (BG), Lombardy, 24047, Italy

Location

GSK Investigational Site

Candiolo (TO), Piedmont, 10060, Italy

Location

GSK Investigational Site

Pisa, Tuscany, 56126, Italy

Location

GSK Investigational Site

Cremona, 26100, Italy

Location

GSK Investigational Site

Pavia, 27100, Italy

Location

GSK Investigational Site

Perugia, 06156, Italy

Location

GSK Investigational Site

Reggio Emilia, 42100, Italy

Location

GSK Investigational Site

Varese, 21100, Italy

Location

GSK Investigational Site

Warsaw, 00-909, Poland

Location

Related Publications (4)

• 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.

  PMID: 22493419 BACKGROUND

• 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.

  PMID: 34153715 DERIVED

• 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.

  PMID: 26245675 DERIVED

• 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.

  PMID: 24590635 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; Trastuzumab; Paclitaxel; Fluorouracil; Epirubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2007
• First Posted: January 31, 2007
• Study Start: August 1, 2006
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: March 22, 2016
• Results First Posted: March 22, 2016

Record last verified: 2016-01

Locations

PL (1); DE (1); IT (15)