Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Amino Acids

Paclitaxel

Albumin-Bound Paclitaxel

Trastuzumab

Fluorouracil

Cyclophosphamide

Epirubicin

Lapatinib

Tubulin Modulators

Antimitotic Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Tyrosine

Chemotherapy plus trastuzumab plus lapatinib

lapatinib

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

trastuzumab

paclitaxel

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

fluorouracil

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

epidoxorubicin

600mg/sqm day 1 q21 days for four courses

cyclophosphamide

GSK Clinical Trials

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

Neoadjuvant Study With Chemotherapy, Lapatinib And Trastuzumab In Breast Cancer

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

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.

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.

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.

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.

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.

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).

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.

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).

GlaxoSmithKline

SAEs and non-serious AEs were collected for all participants who received at least one dose of study medication.

Participants received chemotherapy (CT), which included paclitaxel 80 milligrams per meters squared (mg/m\^2) weekly for 12 weeks, followed by intravenous (IV) fluorouracil 600 mg/m\^2, IV epidoxorubicin 75 mg/m\^2, and IV cyclophosphamide 600 mg/m\^2, once every 21 days for four treatment courses. Trastuzumab was administered throughout the course of the CT and for two weeks after the last CT administration. The first dose of trastuzumab was administered at 4 milligrams per kilogram (mg/kg) IV for 60 minutes on the day of the first paclitaxel course. Subsequent administrations were given weekly at 2 mg/kg IV for 30 minutes. Treatments were administered for 26 weeks prior to surgery.

CT Plus Trastuzumab

Participants received CT, which included paclitaxel 80 mg/m\^2 weekly for 12 weeks, followed by IV fluorouracil 600 mg/m\^2, IV epidoxorubicin 75 mg/m\^2, and IV cyclophosphamide 600 mg/m\^2, once every 21 days for four treatment courses. Participants received lapatinib 1500 mg/day orally on an empty stomach throughout the course of the CT and for three weeks after the last CT administration. Treatments were administered for 26 weeks prior to surgery. Following Independent Data Monitoring Committee (IDMC) recommendations, lapatinib doses were reduced to 1250 mg/day orally on an empty stomach.

CT Plus Lapatinib 1500 mg

Participants received CT, which included paclitaxel 80 mg/m\^2 weekly for 12 weeks, followed by IV fluorouracil 600 mg/m\^2, IV epidoxorubicin 75 mg/m\^2, and IV cyclophosphamide 600 mg/m\^2, once every 21 days for four treatment courses. Trastuzumab was administered throughout the course of the CT and for two weeks after the last CT administration. The first dose of trastuzumab was administered at 4 mg/kg IV for 60 minutes on the day of the first paclitaxel course. Subsequent administrations were given weekly at 2 mg/kg IV for 30 minutes. Participants received lapatinib 1000 mg/day orally on an empty stomach throughout the course of the CT and for three weeks after the last CT administration. Treatments were administered for 26 weeks prior to surgery. Following IDMC recommendations, lapatinib doses were reduced to 750 mg/day orally on an empty stomach.

CT Plus Trastuzumab and Lapatinib 1000 mg

Total

Age, Continuous

Sex: Female, Male

Caucasian

Asian

Unknown

Race/Ethnicity, Customized

GSK Response Center

Participants received CT, which included paclitaxel 80 mg/m\^2 weekly for 12 weeks, followed by IV fluorouracil 600 mg/m\^2, IV epidoxorubicin 75 mg/m\^2, and IV cyclophosphamide 600 mg/m\^2, once every 21 days for four treatment courses. Participants received lapatinib 1500 mg/day orally on an empty stomach throughout the course of the CT and for three weeks after the last CT administration. Treatments were administered for 26 weeks prior to surgery.

Following Independent Data Monitoring Committee (IDMC) recommendations, lapatinib doses were reduced to 1250 mg/day orally on an empty stomach.

Participants received CT, which included paclitaxel 80 mg/m\^2 weekly for 12 weeks, followed by IV fluorouracil 600 mg/m\^2, IV epidoxorubicin 75 mg/m\^2, and IV cyclophosphamide 600 mg/m\^2, once every 21 days for four treatment courses. Trastuzumab was administered throughout the course of the CT and for two weeks after the last CT administration. The first dose of trastuzumab was administered at 4 mg/kg IV for 60 minutes on the day of the first paclitaxel course. Subsequent administrations were given weekly at 2 mg/kg IV for 30 minutes. Participants received lapatinib 1000 mg/day orally on an empty stomach throughout the course of the CT and for three weeks after the last CT administration. Treatments were administered for 26 weeks prior to surgery.

Following IDMC recommendations, lapatinib doses were reduced to 750 mg/day orally on an empty stomach.

Efficacy Analysis Population: all participants in the Intent-to-Treat Population (all participants who were randomized), except for the 2 participants who were excluded because of withdraw of consent and major protocol deviation

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

Complete Response (CR)

Partial Response (PR)

Stable Disease

Progressive Disease

Not Evaluable

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

Mastectomy

Conversion from mastectomy to BCS

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

ITT Population: all participants who were randomized

Time to Treatment Failure From the Start of Primary Therapy

Number of Participants With Treatment Failure

Ki67, Baseline, n=34, 37, 42

Ki67, Post-treatment, n=22, 21, 18

pAKT, Baseline, n=34, 37, 42

pAKT, Post-treatment, 18, 20, 17

pMAPK, Baseline, n=9, 5, 7

pMAPK, Post-treatment, n=0, 1, 2

Tunel test, Baseline, n=25, 27, 31

Tunel test, Post-treatment, n=7, 12, 11

PTEN, Baseline, n=27, 35, 37

PTEN, Post-treatment, n=14, 17, 15

pEGFR, Baseline, n=21, 24, 28

pEGFR, Post-treatment, n=5, 10, 11

ITT Population. Only those participants contributing data to the indicated time points were analyzed.

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

Safety Population: all randomized participants

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

PIK3CA Exon 9 Wild-Type

PIK3CA Exon 9 Mutation

PIK3CA Exon 20 Wild-type

PIK3CA Exon 20 Mutation

ITT Population. Only those participants for which high-quality tumor tissue samples were available were analyzed.

Spots Global Cancer Trial Database for Neoadjuvant Study With Chemotherapy, Lapatinib And Trastuzumab In Breast Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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