Breast CancerPhase 2NCT00256243
Neoadjuvant Biweekly Treatment Followed by Weekly Treatment of Breast Cancer
A Phase 2 study testing Doxorubicin, Cyclophosphamide and Paclitaxel in people with Breast Cancer, run by Rita Sanghvi, Mehta at 1 site in United States.
Trial summary
We proposed to use 4 cycles of AC q 2 weeks, as used in the dose dense adjuvant study with GM-CSF support on days 3-9 of the cycle. After the completion of AC we plan to administer paclitaxel and carboplatin weekly for a total of 12 doses with one week rest after every 3 weeks of treatment over 12 weeks. 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?
- Doxorubicin, Cyclophosphamide and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2004to Jul 2012
- 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
Eligibility Criteria:
- Patients must be women with a histologically confirmed diagnosis of locally advanced or inflammatory breast carcinoma. Histologic confirmation shall be by either core needle biopsy or incisional biopsy. Punch biopsy is allowed if invasive breast cancer is documented.
- Patients must meet one of the criteria defined below (indicate one): a .Selected Stage IIB (T3, N0, M0) or IIIA (T3, N1-2, M0) disease judged primarily unresectable by an experienced breast surgeon; or otherwise deemed appropriate candidates for neoadjuvant treatment.
- Stage IIIB (T4, Any N, M0) or (Any T, N3, M0) disease.
- Physical examination, chest x-ray and any x-rays or scans needed for tumor assessment must be performed within 90 days prior to registration.
- Patients with the clinical diagnosis of congestive heart failure or angina pectoris are NOT eligible. Patients with hypertension or age > 60 years must have a Multiple Gated Acquisition (MUGA) or echocardiogram scan performed within 90 days prior to registration (indicate not applicable (NA) if no MUGA required) and Left Ventricular Ejection Fraction (LVEF) % must be greater than the institutional lower limit of normal.
- Patients must have a serum creatinine and bilirubin ≤ the institutional upper limit of normal, and an Serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic pyruvic transaminase (SGPT) ≤ 2x the institutional upper limit of normal. These tests must have been performed within 90 days prior to registration.
- Patients must have an Absolute neutrophil count (ANC) of ≥ 1,500/μl and a platelet count of ≥ 100,000/μl. These tests must have been performed within 90 days prior to registration.
- Patients must have a performance status of 0-2 by Zubrod criteria
- Pregnant or nursing women may not participate due to the possibility of fetal harm or of harm to nursing infants from this treatment regimen. Women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. A urine pregnancy test is required for women of childbearing potential.
- All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
Trial locations and contacts
1 site in 1 country.
United States1 site
Chao Family Comprehensive Cancer Center
Orange, California, 92868
About this study
Official title: A Pilot Study of Neoadjuvant Biweekly Doxorubicin and Cyclophosphamide (AC) With GMCSF Followed by Weekly Carboplatin/Paclitaxel With Plus or Minus Trastuzumab (TC ± H) in the Treatment of Breast Cancer
We proposed to use 4 cycles of AC q 2 weeks, as used in the dose dense adjuvant study with GM-CSF support on days 3-9 of the cycle. After the completion of AC we plan to administer paclitaxel and carboplatin weekly for a total of 12 doses with one week rest after every 3 weeks of treatment over 12 weeks. Patients who are her-2 over-expressors by FISH (fluorescence in situ hybridization) will also receive Trastuzumab with weekly carboplatin and paclitaxel as the combination TC±H has been found to be synergistic in advanced breast cancer with improved clinical outcome.
Read the detailed description
Neoadjuvant chemotherapy, also termed primary, induction, or preoperative chemotherapy, is defined as chemotherapy administered before locoregional treatment. It was first used in locally advanced breast cancer 30 years ago. Classically, these tumors were treated with radical surgery and/or radiotherapy. However, despite this aggressive local therapy, most patients relapsed with distant metastases and eventually died (1,2). The aim of neoadjuvant therapy is to reduce the tumor volume in patients before surgical resection, thus increasing the likelihood of breast conservation. More recently, neoadjuvant therapy has been studied as a way of testing the relevance of biological markers in predicting disease outcome.
At least six randomized trials have compared survival in patients managed with either the neoadjuvant or adjuvant approaches(3,4,5,6,7,8,9). Two of the smaller trials suggested a survival advantage for patients treated with neoadjuvant chemotherapy (5,6). Other studies, including the largest trial (1523 patients) run by the NSABP, found no differences in disease-free and overall survival (4,6,9).
Induction of a pCR should be one of the primary goals of neoadjuvant therapy because patients with no evidence of tumor cells in breast and lymph nodes after treatment may have a longer disease-free and overall survival (10).
Biweekly and weekly regimens may enhance dose intensity by minimizing re-growth of cells between cycles of treatment. In fact, dose dense regimens have even shown a survival benefit in an adjuvant setting in lymph node positive breast cancer, made possible with use of G-CSF (11). There is as yet no standard best neoadjuvant treatment. Generally patients receive AC (NSABP 14) on 3-weekly regimens in neoadjuvant setting. In addition, incorporation of taxanes on a 3 weekly schedule has resulted in statistically higher pathological CR (12,13). More recently, weekly paclitaxel regimens have reported increased pathological responses compared to 3 weekly taxane regimens. Carboplatin has also emerged as an effective agent in the treatment of metastatic breast cancer (14). Moreover, the combination of carboplatin and paclitaxel has been found to be synergistic both in three-weekly regimens and weekly regimens. In fact, combination of carboplatin, paclitaxel and trastuzumab has demonstrated a survival advantage over paclitaxel and trastuzumab alone. The Phase III study, the preliminary results of which were presented at the San Antonio Breast Cancer Symposium, show that the addition of carboplatin to trastuzumab and paclitaxel resulted in a six-month improvement in the time it took for the disease to progress, compared to the standard trastuzumab and paclitaxel regimen. The study found median survival in the trastuzumab and paclitaxel arm was 33.5 months, while the group receiving the tripartite therapy had yet to reach that point after 36 months of follow-up. Furthermore, the weekly regimens of these drugs have been found to have significantly improved tolerability over three weekly regimens (15). Therefore, we propose to use 4 cycles of AC q 2 weeks, as used in the dose dense adjuvant study with GM-CSF support on days 5-14 of the cycle. After the completion of AC we plan to administer taxol and carboplatin weekly for a total of 9 doses with one week rest after every 3 weeks of treatment over 12 weeks.
Patients who are her-2 overexpressors by FISH will also receive Trastuzumab with weekly carboplatin and paclitaxel as the combination has been found to be synergistic in advanced breast cancer with improved clinical outcome.
In a separate trial, GMCSF was used in breast cancer patients treated with adriamycin based chemotherapy as the preferred growth factor in a neoadjuvant setting (16). The initial results are suggestive of improved survival of breast cancer patients given 6 versus 5 versus 4 cycles of chemotherapy with GMCSF support. Higher dendritic cell (DC) trafficking showed a trend toward improved survival. Moreover, intrapatient comparison before and after treatment showed that the percentage of S100+ DC significantly increased over the course of GM-CSF treatment. The results form the basis of current hypothesis that the primary tumor may be an in vivo antigenic stimulus for dendritic cell trafficking, and that the combination of prolonged neoadjuvant chemotherapy with GM-CSF induced immune enhancement may contribute to better tumor control and better survival.
- Conditions
- Breast Cancer
- Being tested
- Doxorubicin, Cyclophosphamide, Paclitaxel, Carboplatin, GM-CSF
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxorubicinDrug
60 mg/m2 IV, bolus once every 14 days x 2-4 cycles
CyclophosphamideDrug
600 mg/m2 IV once every 14 days x 2-4 cycles
PaclitaxelDrug
80 mg/m2 IV over 1 hour once weekly for 9-12 doses beginning two weeks after completion of last AC dose
CarboplatinDrug
Area under the concentration curve (AUC) 2 IV once weekly for 9-12 doses beginning two weeks after completion of last AC dose
GM-CSFDrug
250 μg/mL IV on day 5-14 of each subcutaneous cycle of doxorubicin and injection cyclophosphamide
TrastuzumabDrug
AUC 2 IV weekly for 12-16 doses beginning two weeks after completion of last AC dose
| Study group | Role | What they receive |
|---|---|---|
| Chemotherapy with GM-CSF | Experimental | Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Carboplatin/Paclitaxel with GM-CSF (day 2-6)
This regimen consists of intravenous administration of doxorubicin (Adriamycin) followed by cyclophosphamide (Cytoxan) every 14 days for a total of four cycles, unless stable disease or clinical progression is documented. Two weeks after completion of the last dose of AC, weekly Carboplatin/paclitaxel will be given for 3 weeks, followed by 1 week of rest, for a total of 12. Each clinic visit will last approximately 1 hour.
Patients who are her-2 overexpressors by FISH will also receive Trastuzumab with weekly carboplatin and paclitaxel as the combination has been found to be synergistic in advanced breast cancer with improved clinical outcome. Receives: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Carboplatin; Drug: GM-CSF; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response Rate
Clinical response (CR): Normal breast on physical exam. No mass, no thickening, no erythema, no peau d'orange.
Measured: 5 years
Secondary outcomes (1)
Microscopic Pathological Response Rate
pathological response rate: No evidence of microscopic invasive tumor at the primary tumor site in the surgical specimen.
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 posted21 Nov 2005 (estimated)
- Study startApr 2004
- Primary completionMar 2011
- Study completionJul 2012
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
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rita Sanghvi, Mehta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Rita Sanghvi, Mehta, University of California, Irvine
- Investigators
- Rita Mehta, MD, Principal investigator, Chao Family Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00256243
- Sponsor's protocol ID
- UCI 03-70
- Other IDs
- 2004-3517
- Status last verified
- Feb 2018
- First submitted
- 17 Nov 2005
- Last updated
- 2 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Neoadjuvant Biweekly Doxorubicin and Cyclophosphamide (AC) With GMCSF Followed by Weekly Carboplatin/Paclitaxel With Plus or Minus Trastuzumab (TC ± H) in the Treatment of Breast Cancer
- ClinicalTrials.gov ID
- NCT00256243
- Acronym / sponsor ID
- UCI 03-70
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Rita Sanghvi, MehtaUniversity, hospital or other
- Study start
- Apr 2004
- Primary completion
- Mar 2011 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 21 Nov 2005 (estimated)
- Results
- Posted 17 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We proposed to use 4 cycles of AC q 2 weeks, as used in the dose dense adjuvant study with GM-CSF support on days 3-9 of the cycle. After the completion of AC we plan to administer paclitaxel and carboplatin weekly for a total of 12 doses with one week rest after every 3 weeks of treatment over 12 weeks. Patients who are her-2 over-expressors by FISH (fluorescence in situ hybridization) will also receive Trastuzumab with weekly carboplatin and paclitaxel as the combination TC±H has been found to be synergistic in advanced breast cancer with improved clinical outcome.
Detailed description
Neoadjuvant chemotherapy, also termed primary, induction, or preoperative chemotherapy, is defined as chemotherapy administered before locoregional treatment. It was first used in locally advanced breast cancer 30 years ago. Classically, these tumors were treated with radical surgery and/or radiotherapy. However, despite this aggressive local therapy, most patients relapsed with distant metastases and eventually died (1,2). The aim of neoadjuvant therapy is to reduce the tumor volume in patients before surgical resection, thus increasing the likelihood of breast conservation. More recently, neoadjuvant therapy has been studied as a way of testing the relevance of biological markers in predicting disease outcome.
At least six randomized trials have compared survival in patients managed with either the neoadjuvant or adjuvant approaches(3,4,5,6,7,8,9). Two of the smaller trials suggested a survival advantage for patients treated with neoadjuvant chemotherapy (5,6). Other studies, including the largest trial (1523 patients) run by the NSABP, found no differences in disease-free and overall survival (4,6,9).
Induction of a pCR should be one of the primary goals of neoadjuvant therapy because patients with no evidence of tumor cells in breast and lymph nodes after treatment may have a longer disease-free and overall survival (10).
Biweekly and weekly regimens may enhance dose intensity by minimizing re-growth of cells between cycles of treatment. In fact, dose dense regimens have even shown a survival benefit in an adjuvant setting in lymph node positive breast cancer, made possible with use of G-CSF (11). There is as yet no standard best neoadjuvant treatment. Generally patients receive AC (NSABP 14) on 3-weekly regimens in neoadjuvant setting. In addition, incorporation of taxanes on a 3 weekly schedule has resulted in statistically higher pathological CR (12,13). More recently, weekly paclitaxel regimens have reported increased pathological responses compared to 3 weekly taxane regimens. Carboplatin has also emerged as an effective agent in the treatment of metastatic breast cancer (14). Moreover, the combination of carboplatin and paclitaxel has been found to be synergistic both in three-weekly regimens and weekly regimens. In fact, combination of carboplatin, paclitaxel and trastuzumab has demonstrated a survival advantage over paclitaxel and trastuzumab alone. The Phase III study, the preliminary results of which were presented at the San Antonio Breast Cancer Symposium, show that the addition of carboplatin to trastuzumab and paclitaxel resulted in a six-month improvement in the time it took for the disease to progress, compared to the standard trastuzumab and paclitaxel regimen. The study found median survival in the trastuzumab and paclitaxel arm was 33.5 months, while the group receiving the tripartite therapy had yet to reach that point after 36 months of follow-up. Furthermore, the weekly regimens of these drugs have been found to have significantly improved tolerability over three weekly regimens (15). Therefore, we propose to use 4 cycles of AC q 2 weeks, as used in the dose dense adjuvant study with GM-CSF support on days 5-14 of the cycle. After the completion of AC we plan to administer taxol and carboplatin weekly for a total of 9 doses with one week rest after every 3 weeks of treatment over 12 weeks.
Patients who are her-2 overexpressors by FISH will also receive Trastuzumab with weekly carboplatin and paclitaxel as the combination has been found to be synergistic in advanced breast cancer with improved clinical outcome.
In a separate trial, GMCSF was used in breast cancer patients treated with adriamycin based chemotherapy as the preferred growth factor in a neoadjuvant setting (16). The initial results are suggestive of improved survival of breast cancer patients given 6 versus 5 versus 4 cycles of chemotherapy with GMCSF support. Higher dendritic cell (DC) trafficking showed a trend toward improved survival. Moreover, intrapatient comparison before and after treatment showed that the percentage of S100+ DC significantly increased over the course of GM-CSF treatment. The results form the basis of current hypothesis that the primary tumor may be an in vivo antigenic stimulus for dendritic cell trafficking, and that the combination of prolonged neoadjuvant chemotherapy with GM-CSF induced immune enhancement may contribute to better tumor control and better survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chemotherapy with GM-CSF | Experimental | Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: Paclitaxel, Drug: Carboplatin, Drug: GM-CSF, Drug: TrastuzumabDoxorubicin and Cyclophosphamide (AC) Followed by Weekly Carboplatin/Paclitaxel with GM-CSF (day 2-6) This regimen consists of intravenous administration of doxorubicin (Adriamycin) followed by cyclophosphamide (Cytoxan) every 14 days for a total of four cycles, unless stable disease or clinical progression is documented. Two weeks after completion of the last dose of AC, weekly Carboplatin/paclitaxel will be given for 3 weeks, followed by 1 week of rest, for a total of 12. Each clinic visit will last approximately 1 hour. Patients who are her-2 overexpressors by FISH will also receive Trastuzumab with weekly carboplatin and paclitaxel as the combination has been found to be synergistic in advanced breast cancer with improved clinical outcome. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Doxorubicin60 mg/m2 IV, bolus once every 14 days x 2-4 cycles | Drug | Chemotherapy with GM-CSF |
| Cyclophosphamide600 mg/m2 IV once every 14 days x 2-4 cycles | Drug | Chemotherapy with GM-CSF |
| Paclitaxel80 mg/m2 IV over 1 hour once weekly for 9-12 doses beginning two weeks after completion of last AC dose | Drug | Chemotherapy with GM-CSF |
| CarboplatinArea under the concentration curve (AUC) 2 IV once weekly for 9-12 doses beginning two weeks after completion of last AC dose | Drug | Chemotherapy with GM-CSF |
| GM-CSF250 μg/mL IV on day 5-14 of each subcutaneous cycle of doxorubicin and injection cyclophosphamide | Drug | Chemotherapy with GM-CSF |
| TrastuzumabAUC 2 IV weekly for 12-16 doses beginning two weeks after completion of last AC dose | Drug | Chemotherapy with GM-CSF |
Primary outcome
Clinical Response Rate
Time frame: 5 years
Clinical response (CR): Normal breast on physical exam. No mass, no thickening, no erythema, no peau d'orange.
1 secondary outcome
Microscopic Pathological Response Rate
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 2 Mar 2018.
- 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.
Rita Mehta, MD principal investigator
Chao Family Comprehensive 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 2 study testing Doxorubicin, Cyclophosphamide and Paclitaxel in people with Breast Cancer, run by Rita Sanghvi, Mehta 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?
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 2 Mar 2018. 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 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 17 Mar 2014). 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?
Clinical Response Rate (time frame: 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 2 Mar 2018.