Breast CancerPhase 2NCT00404066
Phase 2 Neoadjuvant Doxorubicin and Cyclophosphamide -> Docetaxel With Lapatinib in Stage II/III Her2Neu+ Breast Cancer
A Phase 2 study testing Lapatinib, Doxorubicin and Cyclophosphamide in people with Breast Cancer and Metastatic Breast Cancer, run by George Albert Fisher at 2 sites in United States.
Trial summary
This trial combines dose dense chemotherapy with doxorubicin and cyclophosphamide (AC) followed by standard, every 3 week docetaxel and GW572016 (lapatinib) for neoadjuvant treatment of Her2neu positive stage II/III breast cancer. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Breast Cancer, Metastatic Breast Cancer
- What is being tested?
- Lapatinib, Doxorubicin and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2006to Mar 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 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female
- Histologically-confirmed Her2neu positive breast cancer, by either Immunohistochemistry (IHC) 3+ or Fluorescence In Situ Hybridization (FISH)+
- Stage II/III breast cancer including any large primary tumor (> 2 cm), tumors of any size associated with skin or chest wall involvement, tumors of any size with axillary lymph node involvement, (T2-T4, N0-N2) and those with ipsilateral subclavicular or supraclavicular lymph nodes).
- At least one bi-dimensional, measurable indicator lesion.
- Between 18 and 70 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 / Karnofsky ≥ 60% at screening and on the first day of treatment.
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- Informed consent must be obtained prior to registration.
- Cardiac ejection fraction within the institutional range of normal as measured by multigated acquisition (MUGA) or echocardiography (ECHO) scan.
- Absolute neutrophil count > 1,500/mm³
- Hemoglobin > 8.0 g/dL
- Platelet count > 100,000/mm³
- Creatinine within normal institutional limits
- Total Bilirubin equal to or less than institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST); alanine aminotransferase (ALT); and alkaline phosphatase must be within the range allowing for eligibility. In determining eligibility the more abnormal of the two values (AST or ALT) should be used.
- Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of GW572016 will be determined following review of their use by the Principal Investigator
- Antacid use is prohibited 1 hour before and 1 hour after GW572016 dosing.
- All herbal (alternative) medicines are prohibited.
- Medications prohibited during the administration of lapatinib .
- Women of child-bearing potential must have negative pregnancy test and must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation.
- Peripheral neuropathy: must be < grade 1
- Able to swallow and retain oral medication
Who cannot join
- Evidence of disease outside the breast or chest wall, except for ipsilateral axillary , supraclavicular, or infraclavicular lymph nodes.
- Prior chemotherapy, immunotherapy, or hormonal therapy for breast cancer.
- More than 3 months between histologic diagnosis and registration on this study.
- History of other malignancy within the last 5years, except curatively treated basal cell carcinoma of the skin or carcinoma in situ of the cervix.
- Psychological, familial, sociological or geographical conditions which do not permit weekly medical follow-up and compliance with the study protocol. Those who are medically-unstable, including but not limited to active infection, acute hepatitis, deep vein thrombosis requiring anticoagulant therapy, gastrointestinal bleeding, uncontrolled hypercalcemia, uncontrolled diabetes, dementia, seizures, superior vena cava syndrome, and those whose circumstances do not permit completion of the study or the required follow-up.
- Congestive heart failure, abnormal left ventricular ejection fraction (LVEF), angina pectoris, uncontrolled cardiac arrhythmias, or other significant heart disease, or who have had a myocardial infarction within the past year.
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- Pregnant or lactating
- Of childbearing potential and not employing adequate contraception
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016.
- HIV-positive and receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.
- 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).
- History of severe hypersensitivity reaction to taxotere or other drugs formulated with polysorbate 80.
- Current active hepatic or biliary disease (with exception of patients with Gilberts syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment ).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Santa Clara Valley Medical Center
San Jose, California, 95128
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: Phase II Neoadjuvant Chemotherapy Trial in Clinical Stage II/III Her2Neu Positive Breast Cancer With Sequential AC -> Docetaxel With Concurrent Dual EGFR Kinase Blockade by GW572016 (Lapatinib) Followed by 1 Year Adjuvant Trastuzumab
This trial combines dose dense chemotherapy with doxorubicin and cyclophosphamide (AC) followed by standard, every 3 week docetaxel and GW572016 (lapatinib) for neoadjuvant treatment of Her2neu positive stage II/III breast cancer. The purpose of the study was to determine whether lapatinib combined with chemotherapy was safe and resulted in an increase in pathologic complete response rates.
Read the detailed description
Lapatinib acts as a dual inhibitor of both epidermal growth factor receptor (EGFR) and ErbB-2 (Her2/neu) tyrosine kinase activity. EGFR and ErbB2 receptors are frequently over-expressed or altered in human cancers including breast cancer. This study plans to determine the antitumor activity of this regimen and its effectiveness preventing tumor growth and spread.
Neoadjuvant chemotherapy which achieves pathologic complete responses (pCR) has been shown to predict improved long-term survival and serves as a surrogate for clinical outcome. By using this primary endpoint we can obtain statistical data with smaller patient numbers and at a lower overall cost. Additionally, we hope to correlate clinical and radiologic outcomes with gene expression data.
- Conditions
- Breast Cancer, Metastatic Breast Cancer
- Being tested
- Lapatinib, Doxorubicin, Cyclophosphamide, Docetaxel, Pegfilgrastim
- 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
Also called GW572016
1250 mg, tablets, oral daily during treatment with docetaxel (3-week cycles x 4 cycles)
DoxorubicinDrug
Also called Adriamycin, Adriablastin
60 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with cyclophosphamide.
CyclophosphamideDrug
Also called Cytoxan, ASTA
600 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with doxorubicin.
DocetaxelDrug
Also called Taxotere
100 mg/m2, intravenously every 3 weeks for 4 cycles (after treatment cycles of doxorubicin and cyclophosphamide
PegfilgrastimDrug
Also called Neulasta
6 mg, subcutaneously on day 2 of all cytotoxic chemotherapy treatments.
FilgrastimDrug
Also called Neupogen, Granulocyte Colony-Stimulating Factor (G-CSF)
300 or 480 mcg, subcutaneously on days 3 to 10 after cytotoxic chemotherapies.
DexamethasoneDrug
Also called Adexone
8 mg, oral taken twice a day for 3 days starting 24 hours before docetaxel
TrastuzumabDrug
Also called Herceptin
Loading dose 8 mg/kg, then 6 mg/kg, intravenously every 3 weeks for 1 year
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant Chemotherapy | Experimental | Doxorubicin (Adriamycin) + cyclophosphamide (Cytoxan) with pegfilgrastim or filgrastim growth factor support every 2 weeks for 4 cycles, followed by docetaxel + lapatinib for four 21-day cycles, followed by surgery. Dexamethasone was administered twice-a-day for 3 days, starting 24 hours before the docetaxel infusions. After surgery +/- radiation, participants may receive trastuzumab (Herceptin) for a year. Receives: Drug: Lapatinib; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Pegfilgrastim; Drug: Filgrastim; Drug: Dexamethasone; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Pathologic Complete Response (pCR)
Pathologic Complete Response (pCR) rate, assessed as no evidence of invasive disease in excised surgical specimens of breast and/or axilla, in participants who received at least 1 cycle of docetaxel and lapatinib and at least one follow-up evaluation.
Measured: 12 weeks
Secondary outcomes (1)
Disease-free Survival (DFS)
Disease-free survival (DFS) is expressed as the percentage of participants who were disease-free and alive at the time of analysis.
Measured: 42 months (median follow-up)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2006 (estimated)
- Study startOct 2006
- Primary completionDec 2010
- Study completionMar 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 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- George Albert Fisher
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, Sanofi
- Responsible party
- Sponsor-investigator, George Albert Fisher, Stanford University
- Investigators
- George A Fisher, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00404066
- Sponsor's protocol ID
- IRB-03518
- Other IDs
- BRSADJ0002
- Status last verified
- Nov 2017
- First submitted
- 22 Nov 2006
- Last updated
- 22 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Neoadjuvant Chemotherapy Trial in Clinical Stage II/III Her2Neu Positive Breast Cancer With Sequential AC -> Docetaxel With Concurrent Dual EGFR Kinase Blockade by GW572016 (Lapatinib) Followed by 1 Year Adjuvant Trastuzumab
- ClinicalTrials.gov ID
- NCT00404066
- Acronym / sponsor ID
- IRB-03518
- Conditions
- Breast Cancer, Metastatic Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- George Albert FisherUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, Sanofi
- Study start
- Oct 2006
- Primary completion
- Dec 2010 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 27 Nov 2006 (estimated)
- Results
- Posted 22 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial combines dose dense chemotherapy with doxorubicin and cyclophosphamide (AC) followed by standard, every 3 week docetaxel and GW572016 (lapatinib) for neoadjuvant treatment of Her2neu positive stage II/III breast cancer. The purpose of the study was to determine whether lapatinib combined with chemotherapy was safe and resulted in an increase in pathologic complete response rates.
Detailed description
Lapatinib acts as a dual inhibitor of both epidermal growth factor receptor (EGFR) and ErbB-2 (Her2/neu) tyrosine kinase activity. EGFR and ErbB2 receptors are frequently over-expressed or altered in human cancers including breast cancer. This study plans to determine the antitumor activity of this regimen and its effectiveness preventing tumor growth and spread.
Neoadjuvant chemotherapy which achieves pathologic complete responses (pCR) has been shown to predict improved long-term survival and serves as a surrogate for clinical outcome. By using this primary endpoint we can obtain statistical data with smaller patient numbers and at a lower overall cost. Additionally, we hope to correlate clinical and radiologic outcomes with gene expression data.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant Chemotherapy | Experimental | Drug: Lapatinib, Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: Docetaxel, Drug: Pegfilgrastim, Drug: Filgrastim, Drug: Dexamethasone, Drug: TrastuzumabDoxorubicin (Adriamycin) + cyclophosphamide (Cytoxan) with pegfilgrastim or filgrastim growth factor support every 2 weeks for 4 cycles, followed by docetaxel + lapatinib for four 21-day cycles, followed by surgery. Dexamethasone was administered twice-a-day for 3 days, starting 24 hours before the docetaxel infusions. After surgery +/- radiation, participants may receive trastuzumab (Herceptin) for a year. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Female
- Histologically-confirmed Her2neu positive breast cancer, by either Immunohistochemistry (IHC) 3+ or Fluorescence In Situ Hybridization (FISH)+
- Stage II/III breast cancer including any large primary tumor (> 2 cm), tumors of any size associated with skin or chest wall involvement, tumors of any size with axillary lymph node involvement, (T2-T4, N0-N2) and those with ipsilateral subclavicular or supraclavicular lymph nodes).
- At least one bi-dimensional, measurable indicator lesion.
- Between 18 and 70 years of age
Key exclusion criteria (13 listed)
- Evidence of disease outside the breast or chest wall, except for ipsilateral axillary , supraclavicular, or infraclavicular lymph nodes.
- Prior chemotherapy, immunotherapy, or hormonal therapy for breast cancer.
- More than 3 months between histologic diagnosis and registration on this study.
- History of other malignancy within the last 5years, except curatively treated basal cell carcinoma of the skin or carcinoma in situ of the cervix.
- Psychological, familial, sociological or geographical conditions which do not permit weekly medical follow-up and compliance with the study protocol. Those who are medically-unstable, including but not limited to active infection, acute hepatitis, deep vein thrombosis requiring anticoagulant therapy, gastrointestinal bleeding, uncontrolled hypercalcemia, uncontrolled diabetes, dementia, seizures, superior vena cava syndrome, and those whose circumstances do not permit completion of the study or the required follow-up.
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 |
|---|---|---|
| LapatinibAlso: GW5720161250 mg, tablets, oral daily during treatment with docetaxel (3-week cycles x 4 cycles) | Drug | Neoadjuvant Chemotherapy |
| DoxorubicinAlso: Adriamycin, Adriablastin60 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with cyclophosphamide. | Drug | Neoadjuvant Chemotherapy |
| CyclophosphamideAlso: Cytoxan, ASTA600 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with doxorubicin. | Drug | Neoadjuvant Chemotherapy |
| DocetaxelAlso: Taxotere100 mg/m2, intravenously every 3 weeks for 4 cycles (after treatment cycles of doxorubicin and cyclophosphamide | Drug | Neoadjuvant Chemotherapy |
| PegfilgrastimAlso: Neulasta6 mg, subcutaneously on day 2 of all cytotoxic chemotherapy treatments. | Drug | Neoadjuvant Chemotherapy |
| FilgrastimAlso: Neupogen, Granulocyte Colony-Stimulating Factor (G-CSF)300 or 480 mcg, subcutaneously on days 3 to 10 after cytotoxic chemotherapies. | Drug | Neoadjuvant Chemotherapy |
| DexamethasoneAlso: Adexone8 mg, oral taken twice a day for 3 days starting 24 hours before docetaxel | Drug | Neoadjuvant Chemotherapy |
| TrastuzumabAlso: HerceptinLoading dose 8 mg/kg, then 6 mg/kg, intravenously every 3 weeks for 1 year | Drug | Neoadjuvant Chemotherapy |
Primary outcome
Percentage of Participants With Pathologic Complete Response (pCR)
Time frame: 12 weeks
Pathologic Complete Response (pCR) rate, assessed as no evidence of invasive disease in excised surgical specimens of breast and/or axilla, in participants who received at least 1 cycle of docetaxel and lapatinib and at least one follow-up evaluation.
1 secondary outcome
Disease-free Survival (DFS)
Time frame: 42 months (median follow-up)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
George A Fisher, MD, PhD principal investigator
Stanford University
2 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, Doxorubicin and Cyclophosphamide in people with Breast Cancer and Metastatic Breast Cancer, run by George Albert Fisher at 2 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 21 inclusion and 13 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 22 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 22 Dec 2017). 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 Pathologic Complete Response (pCR) (time frame: 12 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 22 Dec 2017.