Neoplasms, BreastPhase 2NCT00422903
Letrozole In Combination With Lapatinib In Neoadjuvant Treatment Of Early Breast Cancer
A Phase 2 study testing lapatinib and letrozole in people with Neoplasms, Breast, run by GlaxoSmithKline at 14 sites in 2 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 80 years, women only
- Conditions the study is for
- Neoplasms, Breast
- What is being tested?
- lapatinib and letrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 92 participants
- Where
- 14 sitesin 2 countries
- Study dates
- Apr 2007to Apr 2011
- 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 80 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 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
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- 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.
Who cannot join
- 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
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- 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)
Trial locations and contacts
14 sites in 2 countries.
14 sites in 2 countries
Italy13 sites
GSK Investigational Site
Brindisi, Apulia, 72100
GSK Investigational Site
Carpi (MO), Emilia-Romagna, 41012
GSK Investigational Site
Chieti, 66100
GSK Investigational Site
Cremona, 26100
GSK Investigational Site
Forlì, Emilia-Romagna, 47100
GSK Investigational Site
Modena, Emilia-Romagna, 41100
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
About this study
Official title: Letrozole Versus Letrozole Plus Lapatinib (GW572016) in Hormone-sensitive, HER-2 Negative Operable Breast Cancer. A Double Blind Randomized Phase II Study With Biomarker Evaluation.
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
- Being tested
- lapatinib, letrozole, placebo
- Keywords
- neo-adjuvant, letrozole, lapatinib, primary breast cancer
- 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
1500 mg administered orally daily
letrozoleDrug
2.5 mg administered orally daily
placeboOther
1500 mg administered orally daily
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: lapatinib; Drug: letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
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.
Measured: 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.
Measured: 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.
Measured: From Baseline (Day 1) up to study withdrawal (approx. 66 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2007 (estimated)
- Study startApr 2007
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neoplasms, BreastStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00422903
- Sponsor's protocol ID
- EGF107692
- Status last verified
- Mar 2016
- First submitted
- 16 Jan 2007
- Last updated
- 12 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Letrozole Versus Letrozole Plus Lapatinib (GW572016) in Hormone-sensitive, HER-2 Negative Operable Breast Cancer. A Double Blind Randomized Phase II Study With Biomarker Evaluation.
- ClinicalTrials.gov ID
- NCT00422903
- Acronym / sponsor ID
- EGF107692
- Conditions
- Neoplasms, Breast
- Keywords
- neo-adjuvant, letrozole, lapatinib, primary breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Apr 2007
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 17 Jan 2007 (estimated)
- Results
- Posted 29 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Evaluate the percentage of clinical objective responses (cOR) in patients with HER2 negative early breast cancer treated with pre operative (neoadjuvant)lapatinib and letrozole
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Letrozole plus placebo | Placebo comparator | Drug: letrozole, Other: placeboLetrozole 2.5 mg administered orally fro 6 mos. plus placebo 1500 mg administered orally throughout the study until definitive surgery |
| Letrozole plus lapatininb | Experimental | Drug: lapatinib, Drug: letrozoleLetrozole 2.5 mg administered orally fro 6 mos. plus lapatinib 1500 mg administered orally throughout the study until definitive surgery |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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)
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lapatinib1500 mg administered orally daily | Drug | Letrozole plus lapatininb |
| letrozole2.5 mg administered orally daily | Drug | Letrozole plus lapatininb, Letrozole plus placebo |
| placebo1500 mg administered orally daily | Other | Letrozole plus placebo |
Primary outcome
Percentage of Participants With Clinical Objective Response (cOR) in the Breast, Evaluated by an Independent Radiological Evaluation Monitoring Committee
Time frame: From Baseline (Day 1) up to 6 months, evaluated every 12 weeks
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.
Percentage of Participants With Various Responses in the Breast, Evaluated Using Per Protocol Criteria
Time frame: From Baseline (Day 1) up to 6 months, evaluated every 12 weeks
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.
8 secondary outcomes
Percentage of Participants With Pathological Complete Response (pCR) in the Breast and Axillary Nodes, Evaluated Using Miller and Payne Criteria
Time frame: At the point of definitive surgery (up to 6 months after Baseline)
Number of Participants With Breast Tumors Per Pathological Stage at Surgery
Time frame: At the point of definitive surgery (up to 6 months after Baseline)
Number of Participants With the Indicated Nodal Status at Surgery
Time frame: At the point of definitive surgery (up to 6 months after Baseline)
Number of Participants With the Indicated Type of Surgery
Time frame: 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
Time frame: 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
Time frame: From Baseline (Day 1) up to 6 months (until definitive surgery)
Mean Left Ventricular Ejection Fraction (LVEF)
Time frame: Baseline (Day 1), after 12 weeks, and after 24 weeks
Time to Treatment Failure From the Start of the Primary Therapy
Time frame: From Baseline (Day 1) up to study withdrawal (approx. 66 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
14 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing lapatinib and letrozole in people with Neoplasms, Breast, run by GlaxoSmithKline at 14 sites in 2 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 15 inclusion and 10 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 12 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Italy, Spain. 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. Some participants in this study may receive a placebo. 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 29 Aug 2012). 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 Clinical Objective Response (cOR) in the Breast, Evaluated by an Independent Radiological Evaluation Monitoring Committee (time frame: From Baseline (Day 1) up to 6 months, evaluated every 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 May 2016.