Breast CancerPhase 2NCT00499681
PhII Neo-Adjuvant Letrozole & Lapatinib in Pts w/HER2+ & Hormone Receptor+ Operable Breast CA SPORE
A Phase 2 study testing lapatinib ditosylate and letrozole in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 4 sites in United States.
Trial summary
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- lapatinib ditosylate and letrozole
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2007to Dec 2010
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical stage I, II, or III operable invasive mammary carcinoma, confirmed by histological analysis
- Measurable residual tumor at the primary site
- Measurable disease is defined as any mass that can be reproducibly measured by physical examination, mammogram, and/or ultrasound and can be accurately measured in at least one dimension (longest diameter to be recorded) as 10 mm (1 cm)
- Available core biopsies from the time of diagnosis
- May include sections of paraffin-embedded material
- Scheduled to undergo surgical treatment with either segmental resection or total mastectomy
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- Prior history of contralateral breast cancer allowed if patient has no evidence of recurrence of their initial primary breast cancer within the last 5 years
- HER2-positive by Herceptest (3+) or FISH
- ER-positive and/or PR-positive by IHC
- Female
- Postmenopausal, as defined by any of the following:
- At least 55 years of age
- Under 55 years of age and amenorrheic for at least 12 months OR follicle-stimulating hormone (FSH) values ≥ 40 IU/L and estradiol levels ≤ 20 IU/L
- Prior bilateral oophorectomy or prior radiation castration with amenorrhea for at least 6 months
- ECOG performance status 0-1
- ANC ≥ 1,000/mm³
- Platelet count ≥ 100,000/mm³
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- AST and ALT ≤ 1.5 times ULN
- Able to swallow and retain oral medication
- Cardiac ejection fraction normal by echocardiogram (or MUGA scan if an echocardiogram cannot be performed or is inconclusive)
Who cannot join
- Locally recurrent breast cancer
- Evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases)
- PATIENT CHARACTERISTICS:
- Premenopausal breast cancer, pregnant, or lactating
- Serious medical illness, that in the judgment of the treating physician, places the patient at high risk of operative mortality
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
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- Ulcerative colitis
- History of other malignancy
- Patients who have been disease-free for 5 years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinomas are eligible
- Active or uncontrolled infection
- Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
- Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure
- PRIOR CONCURRENT THERAPY:
- Prior chemotherapy for primary breast cancer
- Tamoxifen or raloxifene as a preventive agent within the past 21 days
- Hormone replacement therapy (e.g., conjugated estrogens tablets [Premarin]) within the past month
- Prior therapy with anthracyclines
- Investigational drug within the past 30 days or 5 half-lives, whichever is longer
- Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, or any other biologic therapy) other than letrozole
- Concurrent treatment with an investigational agent
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, 37064
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, 37064
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
About this study
Official title: A Phase II Neo-Adjuvant Study of Letrozole in Combination With Lapatinib in Post -Menopausal Patients With HER2-Positive and Hormone Receptor-Positive Operable Breast Cancer
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving letrozole together with lapatinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This randomized phase II trial is studying how well giving letrozole together with lapatinib works in treating postmenopausal women with stage I, stage II, or stage III breast cancer that can be removed by surgery.
Read the detailed description
OBJECTIVES:
Primary
- To determine the pathological complete response in patients with HER2-positive and hormone receptor-positive operable stage I-III breast cancer.
Secondary
- To determine tumor cell apoptosis in situ as measured by TUNEL analysis of tumor sections from fresh frozen or paraffin-embedded core biopsies. (Parts 1 and 2)
- To determine whether EGFR, P-EGFR, P-HER2, Ser118 P-ERα, P-Akt, and P-MAPK (by IHC using fresh frozen or paraffin-embedded core biopsies) predict the inhibition of proliferation in situ (Ki67) and/or induction of cell death (TUNEL). (Parts 1 and 2)
- To determine the safety profile of neoadjuvant letrozole and lapatinib. (Part 2)
- To evaluate tumor response to treatment as measured by ultrasound. (Part 2)
- To evaluate the rate of breast conservation surgery. (Part 2)
- To determine the inhibition in cell proliferation in situ in response to letrozole and lapatinib as measured by the change in percentage of Ki67-positive tumor cells (determined by IHC using tumor sections from fresh frozen or paraffin-embedded surgical material). (Part 2)
OUTLINE: This is a randomized, double-blind, placebo-controlled, two-part study.
- Part 1: Patients are randomized to treatment arm.
- Patients receive lapatinib and letrozole once daily for 2 weeks.
- Patients receive letrozole and placebo once daily for 2 weeks. Patients then proceed to part 2.
- Part 2: All patients receive lapatinib and letrozole once daily for 14 weeks. Patients then undergo surgical resection of disease.
Patients undergo tissue sample collection at baseline, at 2 weeks, and then at the time of surgery for biomarker and laboratory studies. Samples are analyzed by IHC and TUNEL.
- Conditions
- Breast Cancer
- Being tested
- lapatinib ditosylate, letrozole, placebo
- Keywords
- stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB 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.
lapatinib ditosylateDrug
Also called GW572016
Given once daily, 1500mg, for 2 weeks; Given once daily, 1500mg, for 14 weeks in Arm II
letrozoleDrug
Also called Femara
Given once daily, 2.5mg, for 2 weeks; Given once daily, 2.5mg, for 14 weeks
placeboOther
Given once daily for 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive Lapatinib and Letrozole once daily for two weeks, following tumor measurement patients receive Lapatinib and Letrozole once daily for 14 weeks. Receives: Drug: lapatinib ditosylate; Drug: letrozole |
| Arm II | Experimental | Patients receive Letrozole and placebo once daily for 2 weeks, following tumor measurement patients receive Letrozole and Lapatinib once daily for 14 weeks. Receives: Drug: lapatinib ditosylate; Drug: letrozole; Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Pathological Complete Response
Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.
Measured: at 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2007 (estimated)
- Study startJul 2007
- Primary completionOct 2009
- Study completionDec 2010
Why it stopped: slow accrual
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 Breast CancerStudies of the same condition, open and under way.
- 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Ingrid Mayer, MD, Vanderbilt-Ingram Cancer Center
- Investigators
- Ingrid Mayer, MD, Study chair, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00499681
- Sponsor's protocol ID
- VICC BRE 0660
- Other IDs
- VU-VICC-BRE-0660, VU-VICC-061102, GSK-LAP107087
- Status last verified
- Aug 2012
- First submitted
- 10 Jul 2007
- Last updated
- 10 Aug 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Neo-Adjuvant Study of Letrozole in Combination With Lapatinib in Post -Menopausal Patients With HER2-Positive and Hormone Receptor-Positive Operable Breast Cancer
- ClinicalTrials.gov ID
- NCT00499681
- Acronym / sponsor ID
- VICC BRE 0660
- Conditions
- Breast Cancer
- Keywords
- stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jul 2007
- Primary completion
- Oct 2009 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 11 Jul 2007 (estimated)
- Results
- Posted 10 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving letrozole together with lapatinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This randomized phase II trial is studying how well giving letrozole together with lapatinib works in treating postmenopausal women with stage I, stage II, or stage III breast cancer that can be removed by surgery.
Detailed description
OBJECTIVES:
Primary
- To determine the pathological complete response in patients with HER2-positive and hormone receptor-positive operable stage I-III breast cancer.
Secondary
- To determine tumor cell apoptosis in situ as measured by TUNEL analysis of tumor sections from fresh frozen or paraffin-embedded core biopsies. (Parts 1 and 2)
- To determine whether EGFR, P-EGFR, P-HER2, Ser118 P-ERα, P-Akt, and P-MAPK (by IHC using fresh frozen or paraffin-embedded core biopsies) predict the inhibition of proliferation in situ (Ki67) and/or induction of cell death (TUNEL). (Parts 1 and 2)
- To determine the safety profile of neoadjuvant letrozole and lapatinib. (Part 2)
- To evaluate tumor response to treatment as measured by ultrasound. (Part 2)
- To evaluate the rate of breast conservation surgery. (Part 2)
- To determine the inhibition in cell proliferation in situ in response to letrozole and lapatinib as measured by the change in percentage of Ki67-positive tumor cells (determined by IHC using tumor sections from fresh frozen or paraffin-embedded surgical material). (Part 2)
OUTLINE: This is a randomized, double-blind, placebo-controlled, two-part study.
- Part 1: Patients are randomized to treatment arm.
- Patients receive lapatinib and letrozole once daily for 2 weeks.
- Patients receive letrozole and placebo once daily for 2 weeks. Patients then proceed to part 2.
- Part 2: All patients receive lapatinib and letrozole once daily for 14 weeks. Patients then undergo surgical resection of disease.
Patients undergo tissue sample collection at baseline, at 2 weeks, and then at the time of surgery for biomarker and laboratory studies. Samples are analyzed by IHC and TUNEL.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: lapatinib ditosylate, Drug: letrozolePatients receive Lapatinib and Letrozole once daily for two weeks, following tumor measurement patients receive Lapatinib and Letrozole once daily for 14 weeks. |
| Arm II | Experimental | Drug: lapatinib ditosylate, Drug: letrozole, Other: placeboPatients receive Letrozole and placebo once daily for 2 weeks, following tumor measurement patients receive Letrozole and Lapatinib once daily for 14 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Clinical stage I, II, or III operable invasive mammary carcinoma, confirmed by histological analysis
- Available core biopsies from the time of diagnosis
- Scheduled to undergo surgical treatment with either segmental resection or total mastectomy
- Prior history of contralateral breast cancer allowed if patient has no evidence of recurrence of their initial primary breast cancer within the last 5 years
- HER2-positive by Herceptest (3+) or FISH
Key exclusion criteria (20 listed)
- Locally recurrent breast cancer
- Evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases)
- Premenopausal breast cancer, pregnant, or lactating
- Serious medical illness, that in the judgment of the treating physician, places the patient at high risk of operative mortality
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
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 |
|---|---|---|
| lapatinib ditosylateAlso: GW572016Given once daily, 1500mg, for 2 weeks; Given once daily, 1500mg, for 14 weeks in Arm II | Drug | Arm I, Arm II |
| letrozoleAlso: FemaraGiven once daily, 2.5mg, for 2 weeks; Given once daily, 2.5mg, for 14 weeks | Drug | Arm I, Arm II |
| placeboGiven once daily for 2 weeks | Other | Arm II |
Primary outcome
Number of Participants With a Pathological Complete Response
Time frame: at 14 weeks
Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2012.
- 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.
Ingrid Mayer, MD study chair
Vanderbilt-Ingram Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing lapatinib ditosylate and letrozole in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 4 sites in United States.
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 22 inclusion and 20 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: stopped early, as of the sponsor's last update on 10 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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. 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 10 Jul 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?
Number of Participants With a Pathological Complete Response (time frame: at 14 weeks). 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 10 Aug 2012.