Breast CancerPhase 3NCT00038402
Evaluation of the Addition of Herceptin to Standard Chemotherapy in the Neoadjuvant Setting for Operable Breast Cancer
A Phase 3 study testing Herceptin, Taxol and Fluorouracil in people with Breast Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the addition of Herceptin to standard chemotherapy treatment of patients newly diagnosed with operable breast cancer. Other objectives: 1) to evaluate the potential of this therapy to reduce the size of the tumor and increase the possibility of breast conservative surgery, 2)… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Herceptin, Taxol and Fluorouracil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2001to Jul 2011
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All patients with histologic confirmation of invasive, but non-inflammatory carcinoma of the breast with T2-3 (greater than 2 cm), N0-1, M0 will be eligible. Patients with T1N1 (after histological confirmation of nodal disease) will be eligible for the study.
- Histologic confirmation of invasive tumor will be done by core needle biopsy. On the tissue obtained, estrogen and progesterone receptors (ER/PR) as well as Her-2/neu (will be determined by immunohistochemistry (IH) and/or fluorescence in situ hybridization (FISH)) and p53 will be done (for research evaluation). Tumor proliferation rate will be evaluable by immunohistochemistry using paraffin-embedded sections and monoclonal antibody for ki-67. Residual tumor tissue will be saved in the tissue bank for further future studies.
- All patients who are Her-2/neu positive will be eligible for the study. Her-2/neu positivity for protocol purposes will be determined by IHC and patients with tumors that are 3+ or FISH + will be eligible.
- Patients must sign an informed consent indicating that they are aware of the investigational nature of the study, in keeping with institutional policy.
- All patients should have adequate bone marrow function, as defined by peripheral granulocyte count of >1,500/mm3, and platelet count > 100,000 mm3. Patients must have adequate liver function, with a bilirubin within normal laboratory values. In addition, patients should have adequate renal function, defined as serum creatinine <2.0 mg%.
- Patients must have a normal cardiac ejection fraction as determined by baseline echocardiogram. Tape must be saved for review by central cardiologist.
Show all 9Show fewer
- Patients who underwent biopsy outside will be eligible if they had a measurable residual tumor.
- Patients with multicentric disease and extensive Ductal Carcinoma in Situ (DCIS) will be eligible for study.
- Patients with a history of cardiac arrhythmia will be eligible for study after being cleared by cardiology.
Who cannot join
- Patients with T1N0 disease are not eligible for the study.
- Those patients with history of other invasive malignancies will be excluded except non-melanoma skin cancer and non-invasive cervical cancer.
- Patients with a history of congestive heart failure will be excluded.
- Patients who had surgical therapy prior to referral will be ineligible.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to evaluate the addition of Herceptin to standard chemotherapy treatment of patients newly diagnosed with operable breast cancer.
Other objectives: 1) to evaluate the potential of this therapy to reduce the size of the tumor and increase the possibility of breast conservative surgery, 2) evaluate the ability of this regimen to prevent recurrence of breast cancer and impact on survival, 3) determine side effect profile with the addition of Herceptin, and 4) evaluate significance of HER2 expression by two different methods.
Read the detailed description
Participants will receive Herceptin in addition to chemotherapy with Taxol and FEC. 'FEC' is Fluorouracil, Cyclophosphamide and Epirubicin.
During the first course of therapy Herceptin will be given on day 1 through a needle in a vein over 90 minutes. Participants will then be observed for 1 hour after that for harmful side effects. If none occur, later doses of Herceptin will be given over 30 minutes instead of 90 minutes.
On day 2, participants will be given Taxol again through a needle in a vein over 24 hours. Participants will receive the drugs Decadron (dexamethasone), Benadryl (diphenhydramine) and Tagamet (cimetidine) prior to Taxol treatment to prevent allergic reaction due to Taxol. Participants will be observed for 1 hour after starting Taxol for harmful side effects. If none occur, both Taxol and Herceptin can be given on the same day on subsequent courses. Taxol will be premedicated with the same drugs on subsequent courses.
Participants will receive Herceptin weekly for 24 consecutive weeks. Taxol will be given to participants every 3 weeks for 4 courses.
Participants who get a fever or infection during treatment may be given the drug G-CSF. Granulocyte colony-stimulating factor (G-CSF or GCSF) stimulates the bone marrow to make white blood cells, which fight infections.
After Taxol treatment, all participants will receive the drugs fluorouracil, cyclophosphamide, and epirubicin (FEC) through a plastic tube in a vein. Fluorouracil will be given intravenously (IV) as a short infusion on days 1 and 4. Cyclophosphamide will be given intravenously as a short infusion on day 1. Epirubicin will be given IV on day 1. This FEC treatment will be repeated every 3 weeks for a total of 4 treatments. Participants will continue to receive Herceptin weekly during therapy with FEC.
After all FEC treatment is done and surgery is completed, patients with tumors that are sensitive to hormones will begin taking the drug tamoxifen and/or aromatase inhibitors if the patient is postmenopausal. The drug will be given as a pill once a day for 5 years.
Patients will then have surgery to remove all or part of the breast that has cancer. If there are signs that the lymph nodes in the armpit (axilla) contain cancer, these lymph nodes will be removed. Patients may then receive radiation treatment to the breast area and armpit once a day for six weeks.
During the study, participants will have blood tests once a week during the first course of treatment of both Taxol and FEC. In subsequent courses, blood tests will be done prior to administration of chemotherapy. A mammogram and a sonogram will be obtained after Taxol treatment and after FEC treatment. This will help doctors keep track of the tumor size and decide whether to remove all or part of the breast and nearby lymph nodes.
After the study, participants will return for checkups every 4 months during years 1 and 2, every 6 months during year 3, and once a year after that. At each visit, participants will have a complete exam including blood tests and a chest x-ray. Mammography will be done once a year.
Before the study, participants will have a complete exam including blood tests and a chest x-ray. A mammogram and a sonogram of the breast and armpit will be obtained to record tumor size. Small metal clips will be inserted into the breast to mark the tumor if the tumor is shrinking rapidly in response to therapy; in this way, if the tumor disappears after drug treatment, the surgeon can still remove the tissue around the tumor. Sonography of the liver or a CT scan of the abdomen will also be done. In some participants, 3-4 samples of the breast that has tumor will be taken. The samples will be taken using a biopsy needle. An echocardiogram (heart function test) will be done on every participant at baseline. An echocardiogram will be done after finishing their Taxol chemotherapy and another one after finishing FEC chemotherapy. Copies of the echocardiogram tapes may be sent to the sponsor for review. Women who are able to have children will have a pregnancy test.
After having completed therapy, all patients will have a follow-up evaluation of their heart function (same as baseline) 4 months or greater after last treatment.
This is an investigational study. Taxol and Herceptin and all other drugs used in this study are approved by the U. S. Food and Drug Administration. All patients will be treated in the MD Anderson Cancer Center outpatient clinic.
- Conditions
- Breast Cancer
- Being tested
- Herceptin, Taxol, Fluorouracil, Cytoxan, Epirubicin
- Keywords
- Breast Cancer, Non-Inflammatory Breast Cancer, Operable Breast Cancer, Herceptin, Taxol, FEC, Fluorouracil, Cyclophosphamide, Epirubicin, Trastuzumab, Paclitaxel, Neosar
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HerceptinDrug
Also called Trastuzumab
Starting dose of 4 mg/kg by vein, then 2 mg/kg weekly after that until the end of all cycles of neo-adjuvant chemotherapy and during FEC therapy for a total of 24 doses.
TaxolDrug
Also called Paclitaxel
225 mg/m^2 by vein as a continuous infusion over 24 hours each cycle for a total of 4 cycles.
FluorouracilDrug
500 mg/m^2 by vein on Days 1 and 4 for 4 cycles at 3-4 week intervals.
CytoxanDrug
Also called Cyclophosphamide, Neosar
500 mg/m^2 on Day 1 of each cycle for 4 cycles.
EpirubicinDrug
75 mg/m^2 IV on Day 1 of each cycle for 4 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Herceptin + Taxol Followed by FEC | Experimental | Herceptin starting 4 mg/kg intravenous (IV), then 2 mg/kg weekly for all other cycles neo-adjuvant chemotherapy and during FEC therapy for total 24 doses. Taxol 225 mg/m^2 continuous IV over 24 hours each cycle; Fluorouracil 500 mg/m^2 IV Days 1 at 3-4 week intervals; Cytoxan 500 mg/m^2 IV on Day 1; Epirubicin 75 mg/m^2 IV on Day 1. Four 21-day cycles. Receives: Drug: Herceptin; Drug: Taxol; Drug: Fluorouracil; Drug: Cytoxan; Drug: Epirubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Achieved Pathological Complete Remission
Response criteria for Complete Remission defined as disappearance of all clinical evidence of active tumor by clinical evaluation, mammogram and/or ultrasound, and free of all symptoms.
Measured: Baseline to last treatment cycle (approximately 28 weeks, 4 cycles of 21-day intervals of Taxol and up to 4 cycles of FEC for 3-4 week intervals)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2002 (estimated)
- Study startApr 2001
- Primary completionNov 2004
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Aman U Buzdar, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00038402
- Sponsor's protocol ID
- ID99-146
- Status last verified
- Jul 2012
- First submitted
- 30 May 2002
- Last updated
- 20 Jul 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Addition of Herceptin to Standard Chemotherapy in the Neoadjuvant Setting for Operable Breast Cancer
- ClinicalTrials.gov ID
- NCT00038402
- Acronym / sponsor ID
- ID99-146
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer, Non-Inflammatory Breast Cancer, Operable Breast Cancer, Herceptin, Taxol, FEC, Fluorouracil, Cyclophosphamide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Apr 2001
- Primary completion
- Nov 2004 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 31 May 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the addition of Herceptin to standard chemotherapy treatment of patients newly diagnosed with operable breast cancer.
Other objectives: 1) to evaluate the potential of this therapy to reduce the size of the tumor and increase the possibility of breast conservative surgery, 2) evaluate the ability of this regimen to prevent recurrence of breast cancer and impact on survival, 3) determine side effect profile with the addition of Herceptin, and 4) evaluate significance of HER2 expression by two different methods.
Detailed description
Participants will receive Herceptin in addition to chemotherapy with Taxol and FEC. 'FEC' is Fluorouracil, Cyclophosphamide and Epirubicin.
During the first course of therapy Herceptin will be given on day 1 through a needle in a vein over 90 minutes. Participants will then be observed for 1 hour after that for harmful side effects. If none occur, later doses of Herceptin will be given over 30 minutes instead of 90 minutes.
On day 2, participants will be given Taxol again through a needle in a vein over 24 hours. Participants will receive the drugs Decadron (dexamethasone), Benadryl (diphenhydramine) and Tagamet (cimetidine) prior to Taxol treatment to prevent allergic reaction due to Taxol. Participants will be observed for 1 hour after starting Taxol for harmful side effects. If none occur, both Taxol and Herceptin can be given on the same day on subsequent courses. Taxol will be premedicated with the same drugs on subsequent courses.
Participants will receive Herceptin weekly for 24 consecutive weeks. Taxol will be given to participants every 3 weeks for 4 courses.
Participants who get a fever or infection during treatment may be given the drug G-CSF. Granulocyte colony-stimulating factor (G-CSF or GCSF) stimulates the bone marrow to make white blood cells, which fight infections.
After Taxol treatment, all participants will receive the drugs fluorouracil, cyclophosphamide, and epirubicin (FEC) through a plastic tube in a vein. Fluorouracil will be given intravenously (IV) as a short infusion on days 1 and 4. Cyclophosphamide will be given intravenously as a short infusion on day 1. Epirubicin will be given IV on day 1. This FEC treatment will be repeated every 3 weeks for a total of 4 treatments. Participants will continue to receive Herceptin weekly during therapy with FEC.
After all FEC treatment is done and surgery is completed, patients with tumors that are sensitive to hormones will begin taking the drug tamoxifen and/or aromatase inhibitors if the patient is postmenopausal. The drug will be given as a pill once a day for 5 years.
Patients will then have surgery to remove all or part of the breast that has cancer. If there are signs that the lymph nodes in the armpit (axilla) contain cancer, these lymph nodes will be removed. Patients may then receive radiation treatment to the breast area and armpit once a day for six weeks.
During the study, participants will have blood tests once a week during the first course of treatment of both Taxol and FEC. In subsequent courses, blood tests will be done prior to administration of chemotherapy. A mammogram and a sonogram will be obtained after Taxol treatment and after FEC treatment. This will help doctors keep track of the tumor size and decide whether to remove all or part of the breast and nearby lymph nodes.
After the study, participants will return for checkups every 4 months during years 1 and 2, every 6 months during year 3, and once a year after that. At each visit, participants will have a complete exam including blood tests and a chest x-ray. Mammography will be done once a year.
Before the study, participants will have a complete exam including blood tests and a chest x-ray. A mammogram and a sonogram of the breast and armpit will be obtained to record tumor size. Small metal clips will be inserted into the breast to mark the tumor if the tumor is shrinking rapidly in response to therapy; in this way, if the tumor disappears after drug treatment, the surgeon can still remove the tissue around the tumor. Sonography of the liver or a CT scan of the abdomen will also be done. In some participants, 3-4 samples of the breast that has tumor will be taken. The samples will be taken using a biopsy needle. An echocardiogram (heart function test) will be done on every participant at baseline. An echocardiogram will be done after finishing their Taxol chemotherapy and another one after finishing FEC chemotherapy. Copies of the echocardiogram tapes may be sent to the sponsor for review. Women who are able to have children will have a pregnancy test.
After having completed therapy, all patients will have a follow-up evaluation of their heart function (same as baseline) 4 months or greater after last treatment.
This is an investigational study. Taxol and Herceptin and all other drugs used in this study are approved by the U. S. Food and Drug Administration. All patients will be treated in the MD Anderson Cancer Center outpatient clinic.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Herceptin + Taxol Followed by FEC | Experimental | Drug: Herceptin, Drug: Taxol, Drug: Fluorouracil, Drug: Cytoxan, Drug: EpirubicinHerceptin starting 4 mg/kg intravenous (IV), then 2 mg/kg weekly for all other cycles neo-adjuvant chemotherapy and during FEC therapy for total 24 doses. Taxol 225 mg/m^2 continuous IV over 24 hours each cycle; Fluorouracil 500 mg/m^2 IV Days 1 at 3-4 week intervals; Cytoxan 500 mg/m^2 IV on Day 1; Epirubicin 75 mg/m^2 IV on Day 1. Four 21-day cycles. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- All patients with histologic confirmation of invasive, but non-inflammatory carcinoma of the breast with T2-3 (greater than 2 cm), N0-1, M0 will be eligible. Patients with T1N1 (after histological confirmation of nodal disease) will be eligible for the study.
- Histologic confirmation of invasive tumor will be done by core needle biopsy. On the tissue obtained, estrogen and progesterone receptors (ER/PR) as well as Her-2/neu (will be determined by immunohistochemistry (IH) and/or fluorescence in situ hybridization (FISH)) and p53 will be done (for research evaluation). Tumor proliferation rate will be evaluable by immunohistochemistry using paraffin-embedded sections and monoclonal antibody for ki-67. Residual tumor tissue will be saved in the tissue bank for further future studies.
- All patients who are Her-2/neu positive will be eligible for the study. Her-2/neu positivity for protocol purposes will be determined by IHC and patients with tumors that are 3+ or FISH + will be eligible.
- Patients must sign an informed consent indicating that they are aware of the investigational nature of the study, in keeping with institutional policy.
- All patients should have adequate bone marrow function, as defined by peripheral granulocyte count of >1,500/mm3, and platelet count > 100,000 mm3. Patients must have adequate liver function, with a bilirubin within normal laboratory values. In addition, patients should have adequate renal function, defined as serum creatinine <2.0 mg%.
Key exclusion criteria (4 listed)
- Patients with T1N0 disease are not eligible for the study.
- Those patients with history of other invasive malignancies will be excluded except non-melanoma skin cancer and non-invasive cervical cancer.
- Patients with a history of congestive heart failure will be excluded.
- Patients who had surgical therapy prior to referral will be ineligible.
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 |
|---|---|---|
| HerceptinAlso: TrastuzumabStarting dose of 4 mg/kg by vein, then 2 mg/kg weekly after that until the end of all cycles of neo-adjuvant chemotherapy and during FEC therapy for a total of 24 doses. | Drug | Herceptin + Taxol Followed by FEC |
| TaxolAlso: Paclitaxel225 mg/m^2 by vein as a continuous infusion over 24 hours each cycle for a total of 4 cycles. | Drug | Herceptin + Taxol Followed by FEC |
| Fluorouracil500 mg/m^2 by vein on Days 1 and 4 for 4 cycles at 3-4 week intervals. | Drug | Herceptin + Taxol Followed by FEC |
| CytoxanAlso: Cyclophosphamide, Neosar500 mg/m^2 on Day 1 of each cycle for 4 cycles. | Drug | Herceptin + Taxol Followed by FEC |
| Epirubicin75 mg/m^2 IV on Day 1 of each cycle for 4 cycles. | Drug | Herceptin + Taxol Followed by FEC |
Primary outcome
Number of Participants Achieved Pathological Complete Remission
Time frame: Baseline to last treatment cycle (approximately 28 weeks, 4 cycles of 21-day intervals of Taxol and up to 4 cycles of FEC for 3-4 week intervals)
Response criteria for Complete Remission defined as disappearance of all clinical evidence of active tumor by clinical evaluation, mammogram and/or ultrasound, and free of all symptoms.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2012.
- The University of Texas M.D.Anderson Cancer CenterLink provided by the sponsor.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
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.
Aman U Buzdar, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Herceptin, Taxol and Fluorouracil in people with Breast Cancer, run by M.D. Anderson Cancer Center at 1 site 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 9 inclusion and 4 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 20 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 Achieved Pathological Complete Remission (time frame: Baseline to last treatment cycle (approximately 28 weeks, 4 cycles of 21-day intervals of Taxol and up to 4 cycles of FEC for 3-4 week intervals)). 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 20 Jul 2012.