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Evaluate the percentage of clinical objective responses (cOR) in patients with HER2 negative early breast cancer treated with pre operative (neoadjuvant)lapatinib and letrozole
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Letrozole plus placebo | Placebo Comparator | Letrozole 2.5 mg administered orally fro 6 mos. plus placebo 1500 mg administered orally throughout the study until definitive surgery |
|
| Letrozole plus lapatininb | Experimental | Letrozole 2.5 mg administered orally fro 6 mos. plus lapatinib 1500 mg administered orally throughout the study until definitive surgery |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| lapatinib | Drug | 1500 mg administered orally daily |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Clinical Objective Response (cOR) in the Breast, Evaluated by an Independent Radiological Evaluation Monitoring Committee | cOR is defined as the documented evidence of complete response (CR) and partial response (PR) as assessed by ultrasound examination using Response Evaluation Criteria In Solid Tumors (RECIST). CR is defined as the disappearance of all target lesions (TLs) and non-TLs and the appearance of no new lesions (NLs). PR for TLs is defined as a >=30% decrease in the sum of the longest diameter (LD) of TLs, taking as a reference the Baseline sum LD. For non-TLs, it is defined as the persistence of >=1 non-TL and no new TLs or non-TLs. | From Baseline (Day 1) up to 6 months, evaluated every 12 weeks |
| Percentage of Participants With Various Responses in the Breast, Evaluated Using Per Protocol Criteria | Complete clinical response=nodule not detectable; all ultrasound abnormalities detected at diagnosis have disappeared. Partial clinical response=the tumor's longest diameter (LD) is reduced by 50% or more; ultrasound characteristics of the tumor persist. Minimal response=the tumor's LD is reduced by 25%-49%. Stable disease=the tumor's LD is decreased by less than 25% and is increased by no more than 25% from the starting value. Progressive disease=the tumor's LD is increased by more than 25% from the starting value. Participants who were not evaluable did not have data available. | From Baseline (Day 1) up to 6 months, evaluated every 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Pathological Complete Response (pCR) in the Breast and Axillary Nodes, Evaluated Using Miller and Payne Criteria | pCR is defined as the complete absence of infiltrating tumor cells (TCs) in the breast and lymph nodes. Miller and Payne criteria: Grade 1, no change/some alteration to individual malignant cells, but no reduction in overall cellularity; Grade 2, up to a 30% loss in TCs; Grade 3, between an estimated 30% and 90% reduction in TCs; Grade 4, more than a 90% reduction in TCs, only small cluster/dispersed cells remaining; Grade 5, no malignant identifiable cells; carcinoma in the milk ducts may be present. Grades 1 and 2 = No response; Grades 3 and 4= PR; Grade 5 = CR. |
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Inclusion criteria:
Histologically confirmed infiltrating primary breast cancer of 2.0 cm or more in largest clinical diameter
ER and/or PgR positive cancer (> 10% of positive cancer cell assessed by IHC)
Postmenopausal status, defined by at least one of the following:
≥ 60 years of age < 60 years of age and amenorrheic for ≥ 12 months prior to day 1 < 60 years of age and amenorrheic for < 12 months prior to day, or without a uterus: luteinizing hormone (LH) and follicle stimulating hormone (FSH) values within postmenopausal range Prior bilateral oophorectomy Prior radiation castration with amenorrhea for at least 6 months
HER2 negative tumors (IHC 0-2+, or FISH negative)
Availability of tumor tissue suitable for biological and molecular examination before starting primary treatment
Age over 18 years
ECOG PS 0-1
Normal organ and marrow function as defined below:
leukocytes > 3000/mL absolute neutrophil count > 1,500/mL platelets > 100,000/mL total bilirubin within normal institutional limits AST (SGOT)/ALT(SGPT)< 2.5 X institutional upper limit of normal Creatinine within normal institutional limits
A list of medications and substances known or with the potential to interact with CYP450 isoenzymes is provided
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Brindisi | Apulia | 72100 | Italy | ||
| GSK Investigational Site |
Not provided
Not provided
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| ID | Title | Description |
|---|---|---|
| FG000 | Letrozole + Placebo | Letrozole tablets in the dose of 2.5 milligrams (mg) plus matching placebo were administered orally once daily for 6 months prior to surgery. |
| FG001 | Letrozole + Lapatinib | Letrozole tablets in the dose of 2.5 mg plus lapatinib ditosylate monohydrate tablets in the dose of 1500 mg were administered orally once daily for 6 months prior to surgery. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Letrozole + Placebo | Letrozole tablets in the dose of 2.5 milligrams (mg) plus matching placebo were administered orally once daily for 6 months prior to surgery. |
| BG001 | Letrozole + Lapatinib |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Clinical Objective Response (cOR) in the Breast, Evaluated by an Independent Radiological Evaluation Monitoring Committee | cOR is defined as the documented evidence of complete response (CR) and partial response (PR) as assessed by ultrasound examination using Response Evaluation Criteria In Solid Tumors (RECIST). CR is defined as the disappearance of all target lesions (TLs) and non-TLs and the appearance of no new lesions (NLs). PR for TLs is defined as a >=30% decrease in the sum of the longest diameter (LD) of TLs, taking as a reference the Baseline sum LD. For non-TLs, it is defined as the persistence of >=1 non-TL and no new TLs or non-TLs. | Intent-to-Treat (ITT) Population: all participants who entered the study and received at least one dose of letrozole. Three participants withdrew consent and were not included in the efficacy analysis. | Posted | Number | percentage of participants | From Baseline (Day 1) up to 6 months, evaluated every 12 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Letrozole + Placebo | Letrozole tablets in the dose of 2.5 milligrams (mg) plus matching placebo were administered orally once daily for 6 months prior to surgery. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myocardial infarction | Cardiac disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Astenia/Fatigue | General disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D000077341 | Lapatinib |
| D000077289 | Letrozole |
| ID | Term |
|---|---|
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
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| letrozole |
| Drug |
2.5 mg administered orally daily |
|
| placebo | Other | 1500 mg administered orally daily |
|
| At the point of definitive surgery (up to 6 months after Baseline) |
| Number of Participants With Breast Tumors Per Pathological Stage at Surgery | Tumors were categorized as follows: T0, no evidence of primary tumor, but carcinoma of the milk ducts, accumulation of abnormal cells in the breast lobules, or Paget disease (cancer condition that appears like a skin disease involving the breast nipple) with no associated tumor mass; T1, tumor was <=2 centimeters (cm) across; T2, tumor was >2 cm but <5 cm across; T3, tumor was >5 cm across; T4, tumor of any size growing into the chest wall or skin, including inflammatory breast cancer. | At the point of definitive surgery (up to 6 months after Baseline) |
| Number of Participants With the Indicated Nodal Status at Surgery | The nodal status of cancer indicates the involvement of lymph nodes in the participant with cancer. N0 indicates no involvement of lymph nodes, and N+ indicates involvement of lymph nodes. | At the point of definitive surgery (up to 6 months after Baseline) |
| Number of Participants With the Indicated Type of Surgery | Mastectomy is the medical term for the surgical removal of one or both breasts. Breast-conserving surgery (BCS) involves removing only the affected part of the breast tissue during surgery, as opposed to removal of the entire breast. | At the point of definitive surgery (up to 6 months after Baseline 1) |
| Percentage of Participants With Conversion From Planned Mastectomy at Baseline to BCS at Surgery | The percentage of participants who were planned to undergo a mastectomy at baseline but later underwent BCS was measured. | At the point of definitive surgery (up to 6 months after Baseline) |
| Number of Participants With the Indicated Adverse Events With a Classification of >=Grade 2 | Toxicity was measured in grades (severity of the AE) as per National Cancer Institute Common Toxicity Criteria for Adverse Event (NCI CTCAE) version (v) 3.0. The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening/disabling; Grade 5, death related to the AE. Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract, and hypertension is high blood pressure. | From Baseline (Day 1) up to 6 months (until definitive surgery) |
| Mean Left Ventricular Ejection Fraction (LVEF) | Cardiac safety was evaluated as any signs or symptoms of deterioration in LVEF. LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. LVEF was evaluated using NCI CTCAE. | Baseline (Day 1), after 12 weeks, and after 24 weeks |
| Time to Treatment Failure From the Start of the Primary Therapy | Time to treatment failure is calculated as the interval between the date of randomization and the occurrence of local tumor progression (including ipsilateral [on the same side] and controlateral breast tumor progression), distant tumor progression, permanent treatment discontinuation (either for the experimental or conventional treatment arm), or death for any cause. | From Baseline (Day 1) up to study withdrawal (approx. 66 months) |
| Carpi (MO) |
| Emilia-Romagna |
| 41012 |
| Italy |
| GSK Investigational Site | Forlì | Emilia-Romagna | 47100 | Italy |
| GSK Investigational Site | Modena | Emilia-Romagna | 41100 | Italy |
| GSK Investigational Site | Piacenza | Emilia-Romagna | 29100 | Italy |
| GSK Investigational Site | Rimini | Emilia-Romagna | 47900 | Italy |
| GSK Investigational Site | Treviglio (BG) | Lombardy | 24047 | Italy |
| GSK Investigational Site | Pisa | Tuscany | 56126 | Italy |
| GSK Investigational Site | Chieti | 66100 | Italy |
| GSK Investigational Site | Cremona | 26100 | Italy |
| GSK Investigational Site | Perugia | 06156 | Italy |
| GSK Investigational Site | Reggio Emilia | 42100 | Italy |
| GSK Investigational Site | Varese | 21100 | Italy |
| GSK Investigational Site | Badalona | 08916 | Spain |
| Informed Consent Withdrawn |
|
Letrozole tablets in the dose of 2.5 mg plus lapatinib ditosylate monohydrate tablets in the dose of 1500 mg were administered orally once daily for 6 months prior to surgery
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Letrozole + Placebo |
Letrozole tablets in the dose of 2.5 milligrams (mg) plus matching placebo were administered orally once daily for 6 months prior to surgery. |
| OG001 | Letrozole + Lapatinib | Letrozole tablets in the dose of 2.5 mg plus lapatinib ditosylate monohydrate tablets in the dose of 1500 mg were administered orally once daily for 6 months prior to surgery. |
|
|
| Primary | Percentage of Participants With Various Responses in the Breast, Evaluated Using Per Protocol Criteria | Complete clinical response=nodule not detectable; all ultrasound abnormalities detected at diagnosis have disappeared. Partial clinical response=the tumor's longest diameter (LD) is reduced by 50% or more; ultrasound characteristics of the tumor persist. Minimal response=the tumor's LD is reduced by 25%-49%. Stable disease=the tumor's LD is decreased by less than 25% and is increased by no more than 25% from the starting value. Progressive disease=the tumor's LD is increased by more than 25% from the starting value. Participants who were not evaluable did not have data available. | ITT Population. Three participants withdrew consent and were not included in the efficacy analysis. | Posted | Number | percentage of participants | From Baseline (Day 1) up to 6 months, evaluated every 12 weeks |
|
|
|
| Secondary | Percentage of Participants With Pathological Complete Response (pCR) in the Breast and Axillary Nodes, Evaluated Using Miller and Payne Criteria | pCR is defined as the complete absence of infiltrating tumor cells (TCs) in the breast and lymph nodes. Miller and Payne criteria: Grade 1, no change/some alteration to individual malignant cells, but no reduction in overall cellularity; Grade 2, up to a 30% loss in TCs; Grade 3, between an estimated 30% and 90% reduction in TCs; Grade 4, more than a 90% reduction in TCs, only small cluster/dispersed cells remaining; Grade 5, no malignant identifiable cells; carcinoma in the milk ducts may be present. Grades 1 and 2 = No response; Grades 3 and 4= PR; Grade 5 = CR. | ITT Population | Posted | Number | 95% Confidence Interval | Percentage of participants | At the point of definitive surgery (up to 6 months after Baseline) |
|
|
|
| Secondary | Number of Participants With Breast Tumors Per Pathological Stage at Surgery | Tumors were categorized as follows: T0, no evidence of primary tumor, but carcinoma of the milk ducts, accumulation of abnormal cells in the breast lobules, or Paget disease (cancer condition that appears like a skin disease involving the breast nipple) with no associated tumor mass; T1, tumor was <=2 centimeters (cm) across; T2, tumor was >2 cm but <5 cm across; T3, tumor was >5 cm across; T4, tumor of any size growing into the chest wall or skin, including inflammatory breast cancer. | ITT Population. Only those participants contributing data were analyzed. | Posted | Number | participants | At the point of definitive surgery (up to 6 months after Baseline) |
|
|
|
| Secondary | Number of Participants With the Indicated Nodal Status at Surgery | The nodal status of cancer indicates the involvement of lymph nodes in the participant with cancer. N0 indicates no involvement of lymph nodes, and N+ indicates involvement of lymph nodes. | ITT Population. Only those participants contributing data were analyzed. | Posted | Number | participants | At the point of definitive surgery (up to 6 months after Baseline) |
|
|
|
| Secondary | Number of Participants With the Indicated Type of Surgery | Mastectomy is the medical term for the surgical removal of one or both breasts. Breast-conserving surgery (BCS) involves removing only the affected part of the breast tissue during surgery, as opposed to removal of the entire breast. | ITT Population. Only those participants contributing data were analyzed. | Posted | Number | participants | At the point of definitive surgery (up to 6 months after Baseline 1) |
|
|
|
| Secondary | Percentage of Participants With Conversion From Planned Mastectomy at Baseline to BCS at Surgery | The percentage of participants who were planned to undergo a mastectomy at baseline but later underwent BCS was measured. | ITT Population. Only those participants contributing data were analyzed. | Posted | Number | percentage of participants | At the point of definitive surgery (up to 6 months after Baseline) |
|
|
|
| Secondary | Number of Participants With the Indicated Adverse Events With a Classification of >=Grade 2 | Toxicity was measured in grades (severity of the AE) as per National Cancer Institute Common Toxicity Criteria for Adverse Event (NCI CTCAE) version (v) 3.0. The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening/disabling; Grade 5, death related to the AE. Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract, and hypertension is high blood pressure. | ITT Population. Only those participants contributing data were analyzed. | Posted | Number | participants | From Baseline (Day 1) up to 6 months (until definitive surgery) |
|
|
|
| Secondary | Mean Left Ventricular Ejection Fraction (LVEF) | Cardiac safety was evaluated as any signs or symptoms of deterioration in LVEF. LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. LVEF was evaluated using NCI CTCAE. | ITT Population. Only those participants contributing data were analyzed. | Posted | Mean | Full Range | Percent volume | Baseline (Day 1), after 12 weeks, and after 24 weeks |
|
|
|
| Secondary | Time to Treatment Failure From the Start of the Primary Therapy | Time to treatment failure is calculated as the interval between the date of randomization and the occurrence of local tumor progression (including ipsilateral [on the same side] and controlateral breast tumor progression), distant tumor progression, permanent treatment discontinuation (either for the experimental or conventional treatment arm), or death for any cause. | ITT Population. Only those participants contributing data were analyzed. | Posted | Median | 95% Confidence Interval | Months | From Baseline (Day 1) up to study withdrawal (approx. 66 months) |
|
|
|
| 1 |
| 49 |
| 20 |
| 49 |
| EG001 | Letrozole + Lapatinib | Letrozole tablets in the dose of 2.5 mg plus lapatinib ditosylate monohydrate tablets in the dose of 1500 mg were administered orally once daily for 6 months prior to surgery. | 3 | 43 | 36 | 43 |
| Cardiac failure | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Sphincter of Oddi dysfunction | Hepatobiliary disorders | MedDRA | Systematic Assessment |
|
| Overdose | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Spinal cord compression | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Dermatology/Skin | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| LFT transaminases | Investigations | MedDRA | Systematic Assessment |
|
| Mucositis | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Nail changes | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D017437 |
| Skin and Connective Tissue Diseases |
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| Minimal Response |
|
| Stable Disease |
|
| Progressive Disease |
|
| Not Evaluable |
|
| T2 |
|
| T3 |
|
| T4 |
|
| Not done |
|
| Mucositis |
|
| Liver toxicity |
|
| Skin disorders |
|
| Hypertension |
|
| After 24 weeks |
|