Breast CancerPhase 2NRRNCT00006110
Multimodality Treatment for Women With Stage II, Stage III, or Stage IV Breast Cancer
A Phase 2 study testing trastuzumab, cyclophosphamide and doxorubicin hydrochloride in people with Breast Cancer, run by UNC Lineberger Comprehensive Cancer Center at 2 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Read more about this study
- Who is it for?
- Ages 1 year to 120 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- trastuzumab, cyclophosphamide and doxorubicin hydrochloride
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 1998to Apr 2013
- 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 1 year to 120 years
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically confirmed stage IIB, IIIA, IIIB, IIIC, or previously untreated stage IV primary carcinoma of the breast
- Fine needle aspiration, core needle biopsy, or incisional biopsy allowed
- No excisional biopsy
- Any of the following:
- Tumor size 2, Nodes 1 (T2N1) or tumor size 3 nodes 0 (T3N0)
- Any T with N2 (including axillary lymph nodes matted to one another) or N3
Show all 24Show fewer
- Any T4, including inflammatory breast cancer
- Adjuvant patients with at least 4 positive lymph nodes and HER-2 overexpressing tumor
- Supraclavicular or infraclavicular positive lymph nodes without distant metastases
- Distant metastases with measurable disease in breast or lymph nodes
- Synchronous bilateral primary breast cancer allowed if the more serious cancer meets entry criteria
- Measurable or evaluable disease
- PATIENT CHARACTERISTICS:
- Age: Not specified
- Sex: Female
- Menopausal status: Not specified
- Performance status: Not specified
- Life expectancy: Not specified
- Hematopoietic:
- White cell count > 3000 / mm3 Platelet count > 100,000 / mm3
- Hemoglobin > 9 mg / dl Bilirubin < 1.5 x normal Creatinine < 1.5 x normal left ventricular ejection fraction (LVEF) normal by resting nuclear ventriculogram Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception
- Exclusions
- Prior malignancies except:
- Effectively treated squamous cell or basal cell skin cancer Carcinoma in situ of the cervix that has been curatively treated by surgery alone Nonbreast malignancy from which patient has been disease-free for 5 years and is at low risk of recurrence
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599-7305
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, 27157-1082
About this study
Official title: Nonrandomized Ph II Study of Multimodality Therapy for Stg IIB, IIIA/B, or Stg IV Breast Cancer w/4 Cycles of Adriamycin and Cytoxan (AC),Followed by 12 Weeks of Paclitaxel w/ or w/o Herceptin Followed by Local Therapy Followed by Wkly Herceptin or no Additional Therapy
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy, monoclonal antibody therapy, and surgery may be a more effective treatment for breast cancer.
PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy, monoclonal antibody therapy, and surgery in treating women who have stage II, stage III, or stage IV breast cancer.
Read the detailed description
OBJECTIVES:
- Determine the cardiac and other toxicity of paclitaxel when administered with trastuzumab (Herceptin) after doxorubicin and cyclophosphamide in women with stage IIB, IIIA, IIIB, IIIC, or previously untreated stage IV breast cancer.
- Determine whether the addition of paclitaxel with or without trastuzumab to conventional breast cancer adjuvant therapy (doxorubicin and cyclophosphamide) further decreases tumor size and the number of positive axillary nodes in these patients.
- Determine the 5-year disease-free survival and overall survival of patients treated with these regimens.
- Determine whether the initial pathologic response in patients receiving neoadjuvant therapy correlates with the eventual 5-year disease-free survival or overall survival.
- Compare the number of patients eligible for breast-conserving cancer surgery after treatment with doxorubicin and cyclophosphamide vs paclitaxel and trastuzumab.
- Correlate clinical and radiographic response rate with pathologic response rate in the primary tumor and axillary lymph nodes and determine which parameter best determines the pathologic response rate in patients treated with these regimens.
OUTLINE: Patients either received neoadjuvant therapy (HER-2 overexpressing and non-overexpressing patients) or adjuvant therapy (HER-2 overexpressing patients only).
- Neoadjuvant therapy: Patients receive one of two treatment regimens.
- Regimen I (HER-2 non-overexpressing patients or HER-2 overexpressing patients who refuse trastuzumab (Herceptin) therapy): Patients receive doxorubicin IV and cyclophosphamide IV over 30 minutes and paclitaxel IV over 3 hours on day 1 every 3 weeks for a total of 4 courses. Patients then undergo surgery with or without adjuvant radiotherapy and/or oral tamoxifen.
- Regimen II (HER-2 overexpressing patients only): Patients receive doxorubicin and cyclophosphamide as in regimen I. After completion of course 4, patients receive paclitaxel IV and trastuzumab IV over 90-150 minutes weekly on weeks 13-24. Patients then undergo surgery with or without adjuvant radiotherapy. Patients then receive trastuzumab IV over 30 minutes weekly on weeks 29-69 if they did not receive radiotherapy or on weeks 36-76 if they did receive radiotherapy.
- Adjuvant therapy: Patients who receive adjuvant therapy (HER-2 overexpressing patients only) receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1 every 3 weeks for a total of 4 courses. After completion of course 4, patients receive paclitaxel IV and trastuzumab IV over 90 minutes weekly on weeks 13-24. Patients then may undergo radiotherapy followed by trastuzumab IV over 30 minutes weekly on weeks 29-69 if they did not receive radiotherapy or on weeks 36-76 if they did receive radiotherapy.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.
PROJECTED ACCRUAL: A total of 125 patients (100 in the neoadjuvant group and 25 in the adjuvant group) will be accrued for this study within 5 years.
- Conditions
- Breast Cancer
- Being tested
- trastuzumab, cyclophosphamide, doxorubicin hydrochloride, paclitaxel, conventional surgery
- Keywords
- stage II breast cancer, stage IV breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, inflammatory breast cancer
- Medical subject headings
- Breast Neoplasms, Inflammatory Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
trastuzumabBiological
Also called Herceptin
infusion 4 mg/kg load week 1; 2 mg/kg weekly thereafter for 12 weeks
cyclophosphamideDrug
Also called Lyophilized Cytoxan, Endoxan, Cytoxan, Neosar
600 mg/m2, intravenous infusion every 3 weeks for four cycles
Also called Adriamycin
60 mg/m2 intravenously, 5-10 minutes, every 3 weeks, up to 12 weeks
paclitaxelDrug
Also called Taxol
90 mg/m2 weekly, intravenously 1 hour after herceptin, given weekly up to 12 weeks or 175 mg/m2, intravenously every 3 weeks, up to 12 weeks (only if not receiving Herceptin®)
conventional surgeryProcedure or surgery
Surgical excision will take place 12-13 weeks for the neo-adjuvant herceptin setting and 12-13 weeks in the non-herceptin setting. Surgery will take place prior to chemotherapy in the adjuvant herceptin setting
| Study group | Role | What they receive |
|---|---|---|
| Neo-adjuvant Herceptin with or without radiation | Experimental | Chemotherapy followed by Taxol plus Herceptin followed by surgery followed by radiation (or no radiation) followed by additional Herceptin Receives: Biological: trastuzumab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel; Procedure: conventional surgery |
| Non-Herceptin with or without radiation | Experimental | Chemotherapy followed by Taxol followed by surgery followed by radiation (or no radiation) Receives: Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel; Procedure: conventional surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac Toxicity of Weekly Taxol Given With Weekly Herceptin When Delivered Immediately Following Four Cycles of Standard Dose AC.
Doxorubicin + cyclophosphamide in combination with paclitaxel and trastuzumab (AC-TP) Associated Systolic Dysfunction. Systolic function was measured by the ventricular ejection fraction (LVEF). LVEF is a measurement in determining how well your heart is pumping out blood and in diagnosing and tracking heart failure.
Measured: 78 weeks (1.5 years)
Secondary outcomes (2)
Overall Response
Measured by the Overall Response. Response: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: 78 weeks (1.5 years)
Disease-free Survival (DFS) in Patients Receiving and Not Receiving Herceptin®.
Percent of patients receiving and not receiving Herceptin who are alive and disease-free at 5 years.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startDec 1998
- Primary completionMar 2012
- Study completionApr 2013
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.
- More trials run by UNC Lineberger Comprehensive 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lisa A. Carey, MD, Study chair, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006110
- Sponsor's protocol ID
- LCCC 9818
- Other IDs
- LCCC9818, NCI-G00-1836
- Acronym
- NRR
- Status last verified
- Jun 2017
- First submitted
- 3 Aug 2000
- Last updated
- 31 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nonrandomized Ph II Study of Multimodality Therapy for Stg IIB, IIIA/B, or Stg IV Breast Cancer w/4 Cycles of Adriamycin and Cytoxan (AC),Followed by 12 Weeks of Paclitaxel w/ or w/o Herceptin Followed by Local Therapy Followed by Wkly Herceptin or no Additional Therapy
- ClinicalTrials.gov ID
- NCT00006110
- Acronym / sponsor ID
- NRR / LCCC 9818
- Conditions
- Breast Cancer
- Keywords
- stage II breast cancer, stage IV breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, inflammatory breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- Dec 1998
- Primary completion
- Mar 2012 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Posted 31 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy, monoclonal antibody therapy, and surgery may be a more effective treatment for breast cancer.
PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy, monoclonal antibody therapy, and surgery in treating women who have stage II, stage III, or stage IV breast cancer.
Detailed description
OBJECTIVES:
- Determine the cardiac and other toxicity of paclitaxel when administered with trastuzumab (Herceptin) after doxorubicin and cyclophosphamide in women with stage IIB, IIIA, IIIB, IIIC, or previously untreated stage IV breast cancer.
- Determine whether the addition of paclitaxel with or without trastuzumab to conventional breast cancer adjuvant therapy (doxorubicin and cyclophosphamide) further decreases tumor size and the number of positive axillary nodes in these patients.
- Determine the 5-year disease-free survival and overall survival of patients treated with these regimens.
- Determine whether the initial pathologic response in patients receiving neoadjuvant therapy correlates with the eventual 5-year disease-free survival or overall survival.
- Compare the number of patients eligible for breast-conserving cancer surgery after treatment with doxorubicin and cyclophosphamide vs paclitaxel and trastuzumab.
- Correlate clinical and radiographic response rate with pathologic response rate in the primary tumor and axillary lymph nodes and determine which parameter best determines the pathologic response rate in patients treated with these regimens.
OUTLINE: Patients either received neoadjuvant therapy (HER-2 overexpressing and non-overexpressing patients) or adjuvant therapy (HER-2 overexpressing patients only).
- Neoadjuvant therapy: Patients receive one of two treatment regimens.
- Regimen I (HER-2 non-overexpressing patients or HER-2 overexpressing patients who refuse trastuzumab (Herceptin) therapy): Patients receive doxorubicin IV and cyclophosphamide IV over 30 minutes and paclitaxel IV over 3 hours on day 1 every 3 weeks for a total of 4 courses. Patients then undergo surgery with or without adjuvant radiotherapy and/or oral tamoxifen.
- Regimen II (HER-2 overexpressing patients only): Patients receive doxorubicin and cyclophosphamide as in regimen I. After completion of course 4, patients receive paclitaxel IV and trastuzumab IV over 90-150 minutes weekly on weeks 13-24. Patients then undergo surgery with or without adjuvant radiotherapy. Patients then receive trastuzumab IV over 30 minutes weekly on weeks 29-69 if they did not receive radiotherapy or on weeks 36-76 if they did receive radiotherapy.
- Adjuvant therapy: Patients who receive adjuvant therapy (HER-2 overexpressing patients only) receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1 every 3 weeks for a total of 4 courses. After completion of course 4, patients receive paclitaxel IV and trastuzumab IV over 90 minutes weekly on weeks 13-24. Patients then may undergo radiotherapy followed by trastuzumab IV over 30 minutes weekly on weeks 29-69 if they did not receive radiotherapy or on weeks 36-76 if they did receive radiotherapy.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.
PROJECTED ACCRUAL: A total of 125 patients (100 in the neoadjuvant group and 25 in the adjuvant group) will be accrued for this study within 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neo-adjuvant Herceptin with or without radiation | Experimental | Biological: trastuzumab, Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Drug: paclitaxel, Procedure: conventional surgeryChemotherapy followed by Taxol plus Herceptin followed by surgery followed by radiation (or no radiation) followed by additional Herceptin |
| Non-Herceptin with or without radiation | Experimental | Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Drug: paclitaxel, Procedure: conventional surgeryChemotherapy followed by Taxol followed by surgery followed by radiation (or no radiation) |
Who may qualify
- Ages
- 1 year to 120 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (24 listed)
- Histologically confirmed stage IIB, IIIA, IIIB, IIIC, or previously untreated stage IV primary carcinoma of the breast
- Synchronous bilateral primary breast cancer allowed if the more serious cancer meets entry criteria
- Measurable or evaluable disease
- Age: Not specified
- Sex: Female
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| trastuzumabAlso: Herceptininfusion 4 mg/kg load week 1; 2 mg/kg weekly thereafter for 12 weeks | Biological | Neo-adjuvant Herceptin with or without radiation |
| cyclophosphamideAlso: Lyophilized Cytoxan, Endoxan, Cytoxan, Neosar600 mg/m2, intravenous infusion every 3 weeks for four cycles | Drug | Neo-adjuvant Herceptin with or without radiation, Non-Herceptin with or without radiation |
| doxorubicin hydrochlorideAlso: Adriamycin60 mg/m2 intravenously, 5-10 minutes, every 3 weeks, up to 12 weeks | Drug | Neo-adjuvant Herceptin with or without radiation, Non-Herceptin with or without radiation |
| paclitaxelAlso: Taxol90 mg/m2 weekly, intravenously 1 hour after herceptin, given weekly up to 12 weeks or 175 mg/m2, intravenously every 3 weeks, up to 12 weeks (only if not receiving Herceptin®) | Drug | Neo-adjuvant Herceptin with or without radiation, Non-Herceptin with or without radiation |
| conventional surgerySurgical excision will take place 12-13 weeks for the neo-adjuvant herceptin setting and 12-13 weeks in the non-herceptin setting. Surgery will take place prior to chemotherapy in the adjuvant herceptin setting | Procedure or surgery | Neo-adjuvant Herceptin with or without radiation, Non-Herceptin with or without radiation |
Primary outcome
Cardiac Toxicity of Weekly Taxol Given With Weekly Herceptin When Delivered Immediately Following Four Cycles of Standard Dose AC.
Time frame: 78 weeks (1.5 years)
Doxorubicin + cyclophosphamide in combination with paclitaxel and trastuzumab (AC-TP) Associated Systolic Dysfunction. Systolic function was measured by the ventricular ejection fraction (LVEF). LVEF is a measurement in determining how well your heart is pumping out blood and in diagnosing and tracking heart failure.
2 secondary outcomes
Overall Response
Time frame: 78 weeks (1.5 years)
Disease-free Survival (DFS) in Patients Receiving and Not Receiving Herceptin®.
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Clinical trial summary from the NIHLink provided by the sponsor.
- results published in Clinical Breast CancerLink provided by the sponsor.
- 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.
Lisa A. Carey, MD study chair
UNC Lineberger Comprehensive Cancer Center
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 trastuzumab, cyclophosphamide and doxorubicin hydrochloride in people with Breast Cancer, run by UNC Lineberger Comprehensive Cancer Center 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 24 inclusion and 0 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 31 Jul 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 31 Jul 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?
Cardiac Toxicity of Weekly Taxol Given With Weekly Herceptin When Delivered Immediately Following Four Cycles of Standard Dose AC. (time frame: 78 weeks (1.5 years)). 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 31 Jul 2017.