Letrozole In Combination With Lapatinib In Neoadjuvant Treatment Of Early Breast Cancer

NCT00422903 | Completed Phase 2 Results

• 1 other identifier: EGF107692
• Study Type: interventional
• Target: 92
• Locations: 2 countries
• Sites: 14

Brief Summary

Evaluate the percentage of clinical objective responses (cOR) in patients with HER2 negative early breast cancer treated with pre operative (neoadjuvant)lapatinib and letrozole

Conditions

Neoplasms, Breast

Keywords

neo-adjuvant; letrozole; lapatinib; primary breast cancer

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (8)

• Percentage of Participants With Pathological Complete Response (pCR) in the Breast and Axillary Nodes, Evaluated Using Miller and Payne Criteria

  At the point of definitive surgery (up to 6 months after Baseline)

• Number of Participants With Breast Tumors Per Pathological Stage at Surgery

  At the point of definitive surgery (up to 6 months after Baseline)

• Number of Participants With the Indicated Nodal Status at Surgery

  At the point of definitive surgery (up to 6 months after Baseline)

• Number of Participants With the Indicated Type of Surgery

  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

  At the point of definitive surgery (up to 6 months after Baseline)

Study Arms (2)

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

Drug: letrozole; Other: placebo

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

Drug: lapatinib; Drug: letrozole

Interventions

lapatinib DRUG

1500 mg administered orally daily

Letrozole plus lapatininb

letrozole DRUG

2.5 mg administered orally daily

Letrozole plus lapatininb; Letrozole plus placebo

placebo OTHER

1500 mg administered orally daily

Letrozole plus placebo

Eligibility Criteria

• Age: 18 Years - 80 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 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
• 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
• Ability to understand and the willingness to sign a written informed consent document.
• Ability to swallow and retain oral medication.

You may not qualify if:

• Stage IIIB, IIIC, and inflammatory breast cancer
• Stage IV breast cancer
• Contraindication to the treatment with letrozole
• 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
• 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 (See section 3.7.4.2 Other concomitant treatments)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (14)

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

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

Pisa, Tuscany, 56126, Italy

Location

GSK Investigational Site

Chieti, 66100, Italy

Location

GSK Investigational Site

Cremona, 26100, 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

Badalona, 08916, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; Letrozole

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; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2007
• First Posted: January 17, 2007
• Study Start: April 1, 2007
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: May 12, 2016
• Results First Posted: August 29, 2012

Record last verified: 2016-03

Locations

ES (1); IT (13)