Breast NeoplasmsPhase 2NCT01498588
Trial of Eribulin Followed by Doxorubicin & Cyclophosphamide for Her2-negative, Locally Advanced Breast Cancer
A Phase 2 study testing Eribulin, Doxorubicin and Cyclophosphamide in people with Breast Neoplasms and Breast Cancer, run by Emory University at 4 sites in United States.
Trial summary
Previous studies have shown that chemotherapy has the same effect on treating breast cancer whether you receive it before or after surgery. Receiving chemotherapy before surgery, rather than after surgery, may allow the patient to have less extensive surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Neoplasms, Breast Cancer, Breast Tumors
- What is being tested?
- Eribulin, Doxorubicin and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 4 sitesUnited States
- Study dates
- Nov 2011to Jun 2015
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed invasive breast carcinoma.
- Locally advanced breast cancer (Stage IIIA to IIIC).
- Invasive breast cancer must be Her2-negative. If breast cancer is Her2 2+ by immunohistochemistry (IHC), then fluorescence in situ hybridization (FISH) must be negative for Her2 gene amplification.
- No evidence of disease outside the breast or chest wall, except ipsilateral axillary lymph nodes on staging scans (CT chest/abdomen/pelvis and bone scan or positron emission tomography [PET] scan).
- Patients must have measurable disease as defined by palpable lesion with both diameters ≥ 1 cm measurable with caliper and/or a positive mammogram or ultrasound with at least one dimension ≥ 1 cm. Bilateral mammogram and clip placement is required for study entry. Baseline measurements of the indicator lesions must be recorded on the Patient Registration Form. To be valid for baseline, the measurements must have been made within the 14 days if palpable. If not palpable, a mammogram or MRI must be done within 14 days. If palpable, a mammogram or MRI must be done within 2 months prior to study entry. If clinically indicated, xrays and scans must be done within 28 days of study entry.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 within 14 days of study entry.
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- Normal (greater than 50%) left ventricular ejection fraction (LVEF) by multigated acquisition (MUGA) scan or echocardiography.
- Signed informed consent.
- Adequate organ function within 2 weeks of study entry:
- Absolute neutrophil count ≥ 1500/mm³, Hgb ≥ 9.0 g/dl and platelet count ≥ 100,000/mm³.
- Total bilirubin ≤ upper limit of normal.
- Creatinine ≤ 1.5 mg/dL or calculated creatinine clearance rate (CrCL) ≥ 50 mL/min using the Cockroft Gault equation.
- Serum glutamate oxaloacetate transaminase (SGOT)/(AST) or serum glutamate pyruvate transaminase (SGPT)/(ALT) and alkaline phosphatase (alk phos) must be within the range allowing for eligibility.
- Patients must be over 18 years old.
- International normalized ratio (INR) < 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate.
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
- Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation.
- Patient must have signed informed consent prior to registration on this study.
Who cannot join
- Prior chemotherapy, hormonal therapy, biologic therapy, investigational agent, targeted therapy or radiation therapy for current breast cancer. Patients with history of breast cancer greater than 5 years from initial diagnosis are eligible for the study. Patients may not have received anthracycline-based chemotherapy in the past. Patients with history of ductal carcinoma in situ (DCIS) are eligible if there were treated with surgery alone.
- Medical, psychological or surgical condition which the investigator feels might compromise study participation.
- History of previous or current malignancy at other sites with the exception of adequately treated carcinoma in-situ of the cervix or basal or squamous cell carcinoma of the skin. Patients with a history of other malignancies, who remain disease free for greater than five years are eligible.
- Evidence of sensory and/or peripheral neuropathy > grade 1.
- Serious, uncontrolled, concurrent infection(s).
- Major surgery within 4 weeks of the start of study treatment, without complete recovery.
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- Pregnant or lactating women are not eligible. Women of childbearing potential must have a negative serum or urine pregnancy test completed within 7 days of study treatment. Women or men of childbearing potential not using a reliable and appropriate contraceptive method are not eligible. (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential).
- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
- Active clinically serious infection > CTCAE Grade 2.
- Thromboembolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
- Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug.
- Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug.
- Cardiac disease: congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Grady Memorial Hospital
Atlanta, Georgia, 30303
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
About this study
Official title: Phase II Neoadjuvant Trial of Eribulin Followed by Dose Dense Doxorubicin and Cyclophosphamide for Her2-negative, Locally Advanced Breast Cancer
Previous studies have shown that chemotherapy has the same effect on treating breast cancer whether you receive it before or after surgery. Receiving chemotherapy before surgery, rather than after surgery, may allow the patient to have less extensive surgery. The purpose of this study is to identify new treatment regimens with better response rates and to find out if the combination of eribulin followed by doxorubicin and cyclophosphamide can shrink the size of the patient's breast tumor and allow you to preserve your breast. Additionally, by receiving chemotherapy before surgery, the investigators will be able to determine if your cancer is responsive to chemotherapy.
Read the detailed description
This is a phase 2, single-arm, open label study. Patients with Her2-negative, locally advanced breast cancer will be enrolled on the study prior to receiving neoadjuvant chemotherapy. Patients will receive 4 cycles of neoadjuvant eribulin followed by 4 cycles of dose-dense doxorubicin and cyclophosphamide (AC).
All patients will have a baseline biopsy prior to study entry to determine eligibility. Patients will undergo repeat breast imaging and optional biopsy after completing 4 cycles of eribulin. Patients will then receive 4 cycles of dose-dense AC. Patients will undergo repeat breast imaging followed by surgical resection within 30 days of completing last cycle of chemotherapy. Patients who are not surgical candidates after completion of chemotherapy will be asked to undergo optional repeat biopsy prior to receiving additional treatment at the discretion of the investigator. Patients will continue to be followed per standard practice guideline after surgery
Clinical response will be determined by clinical breast examination prior to each cycle of chemotherapy and by breast imaging performed at baseline, after completion of eribulin, and prior to surgery. Pathologic complete response (pCR) will be determined at the time of surgical resection. Correlative biomarker studies will be performed on tumor samples at the completion of the clinical trial.
- Conditions
- Breast Neoplasms, Breast Cancer, Breast Tumors, Cancer of the Breast, Neoplasms, Breast, Tumors, Breast
- Being tested
- Eribulin, Doxorubicin, Cyclophosphamide, Pegfilgrastim
- Keywords
- Breast Neoplasms, Breast Cancer, Breast Tumors, Cancer of the Breast, Neoplasms, Breast, Tumors, Breast
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EribulinDrug
Also called Halaven
Patients will receive 4 cycles of neoadjuvant eribulin followed by 4 cycles of dose-dense doxorubicin and cyclophosphamide (AC).
DoxorubicinDrug
Also called Adriamycin
Neoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide
CyclophosphamideDrug
Also called Cytoxan
Neoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide
PegfilgrastimDrug
Also called Neulasta
Growth factor support (pegfilgrastim) can be given at the discretion of the investigator. Administration of pegfilgrastim is required 24 to 48 hours following administration of dose-dense doxorubicin and cyclophosphamide.
| Study group | Role | What they receive |
|---|---|---|
| Eribulin+Doxorubicin+Cyclophosphamide | Experimental | Neoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide
Eribulin Day 1 and Day 8 of a 21 day cycle x 4 cycles:
Day 1: Eribulin 1.4mg/m² IV
Day 8: Eribulin 1.4mg/m² IV
Dose-dense doxorubicin and cyclophosphamide every 14 days x 4 cycles:
Day 1: Doxorubicin 60mg/m² IV
Day 1: Cyclophosphamide 600mg/m² IV
Day 2: Pegfilgrastim support 6mg sc at least 24 hours after chemotherapy at the discretion of the investigator. Receives: Drug: Eribulin; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Pegfilgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response Rate at the Time of Surgery
Patients will receive treatment for 20 weeks with primary outcome measured at the time of surgery. Surgery is typically 4-6 weeks after completion of chemotherapy, so patients will be on study for 24 weeks on average. Response was measured by pathologist's standard of care assessment of extent of residual disease. If the patient had no evidence of invasive or in situ residual disease present in the breast and lymph node (i.e. ypT0N0), then this was defined as a pathologic complete response (pCR). Reported is the number of participants showing pCR.
Measured: Average of 24 weeks
Secondary outcomes (1)
Toxicity of Chemotherapy Regimen (Number of Participants With Any Adverse Events)
Toxicity of chemotherapy at each physician visit using Common Toxicity Criteria for Adverse Effects (CTCAE) criteria.
Measured: Through 20 weeks of chemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2011 (estimated)
- Study startNov 2011
- Primary completionJun 2015
- Study completionJun 2015
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Eisai Inc.
- Responsible party
- Principal investigator, Keerthi Gogineni, Emory University
- Investigators
- Keerthi Gogineni, MD, MSHP, Principal investigator, Emory University Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01498588
- Sponsor's protocol ID
- IRB00050068
- Other IDs
- WCI1937-10
- Status last verified
- Sep 2016
- First submitted
- 13 Oct 2011
- Last updated
- 3 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Neoadjuvant Trial of Eribulin Followed by Dose Dense Doxorubicin and Cyclophosphamide for Her2-negative, Locally Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT01498588
- Acronym / sponsor ID
- IRB00050068
- Conditions
- Breast Neoplasms, Breast Cancer, Breast Tumors, Cancer of the Breast, Neoplasms, Breast, Tumors, Breast
- Keywords
- Breast Neoplasms, Breast Cancer, Breast Tumors, Cancer of the Breast, Neoplasms, Breast, Tumors, Breast
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Eisai Inc.
- Study start
- Nov 2011
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 23 Dec 2011 (estimated)
- Results
- Posted 3 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Previous studies have shown that chemotherapy has the same effect on treating breast cancer whether you receive it before or after surgery. Receiving chemotherapy before surgery, rather than after surgery, may allow the patient to have less extensive surgery. The purpose of this study is to identify new treatment regimens with better response rates and to find out if the combination of eribulin followed by doxorubicin and cyclophosphamide can shrink the size of the patient's breast tumor and allow you to preserve your breast. Additionally, by receiving chemotherapy before surgery, the investigators will be able to determine if your cancer is responsive to chemotherapy.
Detailed description
This is a phase 2, single-arm, open label study. Patients with Her2-negative, locally advanced breast cancer will be enrolled on the study prior to receiving neoadjuvant chemotherapy. Patients will receive 4 cycles of neoadjuvant eribulin followed by 4 cycles of dose-dense doxorubicin and cyclophosphamide (AC).
All patients will have a baseline biopsy prior to study entry to determine eligibility. Patients will undergo repeat breast imaging and optional biopsy after completing 4 cycles of eribulin. Patients will then receive 4 cycles of dose-dense AC. Patients will undergo repeat breast imaging followed by surgical resection within 30 days of completing last cycle of chemotherapy. Patients who are not surgical candidates after completion of chemotherapy will be asked to undergo optional repeat biopsy prior to receiving additional treatment at the discretion of the investigator. Patients will continue to be followed per standard practice guideline after surgery
Clinical response will be determined by clinical breast examination prior to each cycle of chemotherapy and by breast imaging performed at baseline, after completion of eribulin, and prior to surgery. Pathologic complete response (pCR) will be determined at the time of surgical resection. Correlative biomarker studies will be performed on tumor samples at the completion of the clinical trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eribulin+Doxorubicin+Cyclophosphamide | Experimental | Drug: Eribulin, Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: PegfilgrastimNeoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide Eribulin Day 1 and Day 8 of a 21 day cycle x 4 cycles: Day 1: Eribulin 1.4mg/m² IV Day 8: Eribulin 1.4mg/m² IV Dose-dense doxorubicin and cyclophosphamide every 14 days x 4 cycles: Day 1: Doxorubicin 60mg/m² IV Day 1: Cyclophosphamide 600mg/m² IV Day 2: Pegfilgrastim support 6mg sc at least 24 hours after chemotherapy at the discretion of the investigator. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Histologically or cytologically confirmed invasive breast carcinoma.
- Locally advanced breast cancer (Stage IIIA to IIIC).
- Invasive breast cancer must be Her2-negative. If breast cancer is Her2 2+ by immunohistochemistry (IHC), then fluorescence in situ hybridization (FISH) must be negative for Her2 gene amplification.
- No evidence of disease outside the breast or chest wall, except ipsilateral axillary lymph nodes on staging scans (CT chest/abdomen/pelvis and bone scan or positron emission tomography [PET] scan).
- Patients must have measurable disease as defined by palpable lesion with both diameters ≥ 1 cm measurable with caliper and/or a positive mammogram or ultrasound with at least one dimension ≥ 1 cm. Bilateral mammogram and clip placement is required for study entry. Baseline measurements of the indicator lesions must be recorded on the Patient Registration Form. To be valid for baseline, the measurements must have been made within the 14 days if palpable. If not palpable, a mammogram or MRI must be done within 14 days. If palpable, a mammogram or MRI must be done within 2 months prior to study entry. If clinically indicated, xrays and scans must be done within 28 days of study entry.
Key exclusion criteria (16 listed)
- Prior chemotherapy, hormonal therapy, biologic therapy, investigational agent, targeted therapy or radiation therapy for current breast cancer. Patients with history of breast cancer greater than 5 years from initial diagnosis are eligible for the study. Patients may not have received anthracycline-based chemotherapy in the past. Patients with history of ductal carcinoma in situ (DCIS) are eligible if there were treated with surgery alone.
- Medical, psychological or surgical condition which the investigator feels might compromise study participation.
- History of previous or current malignancy at other sites with the exception of adequately treated carcinoma in-situ of the cervix or basal or squamous cell carcinoma of the skin. Patients with a history of other malignancies, who remain disease free for greater than five years are eligible.
- Evidence of sensory and/or peripheral neuropathy > grade 1.
- Serious, uncontrolled, concurrent infection(s).
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 |
|---|---|---|
| EribulinAlso: HalavenPatients will receive 4 cycles of neoadjuvant eribulin followed by 4 cycles of dose-dense doxorubicin and cyclophosphamide (AC). | Drug | Eribulin+Doxorubicin+Cyclophosphamide |
| DoxorubicinAlso: AdriamycinNeoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide | Drug | Eribulin+Doxorubicin+Cyclophosphamide |
| CyclophosphamideAlso: CytoxanNeoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide | Drug | Eribulin+Doxorubicin+Cyclophosphamide |
| PegfilgrastimAlso: NeulastaGrowth factor support (pegfilgrastim) can be given at the discretion of the investigator. Administration of pegfilgrastim is required 24 to 48 hours following administration of dose-dense doxorubicin and cyclophosphamide. | Drug | Eribulin+Doxorubicin+Cyclophosphamide |
Primary outcome
Pathologic Complete Response Rate at the Time of Surgery
Time frame: Average of 24 weeks
Patients will receive treatment for 20 weeks with primary outcome measured at the time of surgery. Surgery is typically 4-6 weeks after completion of chemotherapy, so patients will be on study for 24 weeks on average. Response was measured by pathologist's standard of care assessment of extent of residual disease. If the patient had no evidence of invasive or in situ residual disease present in the breast and lymph node (i.e. ypT0N0), then this was defined as a pathologic complete response (pCR). Reported is the number of participants showing pCR.
1 secondary outcome
Toxicity of Chemotherapy Regimen (Number of Participants With Any Adverse Events)
Time frame: Through 20 weeks of chemotherapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2016.
- 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.
Keerthi Gogineni, MD, MSHP principal investigator
Emory University Winship Cancer Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eribulin, Doxorubicin and Cyclophosphamide in people with Breast Neoplasms and Breast Cancer, run by Emory University at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Oct 2016). 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?
Pathologic Complete Response Rate at the Time of Surgery (time frame: Average of 24 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 3 Oct 2016.