HER2 Negative Breast CancerPhase 2NCT01527487
Trial of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Locally Advanced HER2-Negative Breast Cancer
A Phase 2 study testing Eribulin, Cyclophosphamide and Docetaxel in people with HER2 Negative Breast Cancer, run by SCRI Development Innovations, LLC at 15 sites in United States.
Trial summary
The investigators propose a randomized phase II study evaluating the pCR and toxicity profiles of combination eribulin/cyclophosphamide (ErC) and docetaxel /cyclophosphamide (TC) as neoadjuvant therapy for locally advanced HER2-negative breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- HER2 Negative Breast Cancer
- What is being tested?
- Eribulin, Cyclophosphamide and Docetaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 15 sitesUnited States
- Study dates
- Jun 2012to Jul 2016
- 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
Who may be able to join
- Histologically confirmed invasive adenocarcinoma of the breast.
- Primary palpable disease confined to the breast and axilla on physical examination (clinical Stage II or III disease). For patients without clinically suspicious axillary adenopathy, the primary must be >2 cm in diameter by physical examination or imaging studies (clinical T2-3, N0-2, M0). For patients with clinically suspicious axillary adenopathy, the primary breast tumor can be any size (clinical T1-3, N1-2, M0). Patients who have had axillary node dissection and have pN3a (i.e. ≥10 involved axillary nodes) are also eligible.
- Patients entering the trial after undergoing an axillary node dissection will be eligible if they meet other entry criteria.
- Estrogen receptor (ER) and progesterone receptor (PR) status in the primary tumor known or pending at the time of study registration.
- Resolution of all acute effects of surgical procedures to ≤ grade 1. For patients who had or will have, a sentinel node and/or axillary node dissection, completion at least 1 week prior to the initiation of study treatment with a well-healed wound is required.
- Bilateral, synchronous breast cancer is allowed if both primary tumors are HER2-negative and at least one meets the specified qualifying tumor or nodal inclusion criteria.
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- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-2.
- Patients entering this study must be willing to provide release of tumor tissue collected at baseline during a diagnostic procedure if available, and at the time of future surgical procedure(s) for correlative testing. If tissue is not available, the patient will still be eligible for enrollment to the study.
- No evidence of metastatic disease, as documented by complete staging workup ≤8 weeks prior to initiation of study treatment.
- No prior treatment for this breast cancer with the exception of criterion #3.
- HER2-negative tumor status defined as:
- Immunohistochemical (IHC) 0-1+ or
- IHC 2+ or IHC 3+ confirmed as FISH (Fluorescence in situ hybridization) or SISH (Silver in situ hybridization) negative (defined by ratio <2.2)
- Adequate hematologic function defined as:
- Absolute neutrophil count (ANC) ≥1500/μL
- Hemoglobin (Hgb) ≥10 g/dL
- Platelets ≥100,000/uL
- Adequate liver function defined as:
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the upper limit of normal (ULN)
- Total bilirubin ≤ the institutional ULN
- Adequate renal function defined as:
- Serum creatinine ≤1.5 mg/dL x ULN OR calculated creatinine clearance ≥50 mL/min by the Cockcroft-Gault method:
- GRF =(140-age) x (weight/kg) x (0.85 if female) (72 x serum creatinine mg/dL)
- Other laboratory testing:
- Serum magnesium ≥ the institutional lower limit of normal (LLN)
- Serum potassium ≥the institutional LLN
- Female and ≥18 years of age.
- Negative serum pregnancy test within <7 days prior to initial trial treatment.
- Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures that are approved by their study physician while receiving study treatment and continuing for 3 weeks after the last dose of study drug treatment, who are not breastfeeding, and who have a negative serum pregnancy test prior to start of dosing.
- Willingness and ability to comply with trial and follow-up procedures.
- Ability to understand the nature of this trial and give written informed consent.
Who cannot join
- Clinical T4 lesions, including inflammatory breast cancer. Clinical N3 involvement (e.g., ipsilateral, infraclavicular, supraclavicular, and internal mammary nodes).
- Peripheral neuropathy (motor or sensory) > grade 1 according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
- Patient has received radiotherapy for treatment of previous cancer that included ≥30% of major bone marrow containing areas (e.g., pelvis, lumbar, spine).
- Known or suspected allergy or hypersensitivity to any of the study drugs (i.e., eribulin, cyclophosphamide, docetaxel) or known hypersensitivity to polysorbate 80.
- Patients with acute or chronic liver or renal disease or pancreatitis.
- Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV).
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- Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Patients must have discontinued use of such agents prior to beginning study treatment. However, use of GNRH agonists for the purpose of fertility preservation or suppression of heavy menses is permitted (see Section 5.4.1).
- Patient has any of the following cardiac diseases currently or within the last 6 months:
- Left Ventricular Ejection Fraction (LVEF) <45% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
- Heart rate-corrected QT interval (QTc) > 480 ms on screening electrocardiogram (ECG) (using Bazett's formula)
- Unstable angina pectoris
- Congestive heart failure (New York Heart Association [NYHA] ≥ Grade 2
- Acute myocardial infarction
- Conduction abnormality not controlled with pacemaker or medication
- Significant ventricular or supraventricular arrhythmias (Patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
- Valvular disease with significant compromise in cardiac function
- Chronic use of drugs that cause QTc prolongation. Patients must discontinue use of these drugs 7 days prior to the start of study treatment.
- Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
- Patients may not receive any other investigational or anti-cancer treatments while participating in this trial.
- Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817
Oncology Hematology Care, Inc
Cincinnati, Ohio, 45242
South Carolina Oncology Associates
Columbia, South Carolina, 29210
Florida Cancer Specialists South
Fort Myers, Florida, 33916
The Center for Cancer and Blood Disorders
Fort Worth, Texas, 76104
Northeast Georgia Medical Center
Gainesville, Georgia, 30501
Grand Rapids Oncology Program
Grand Rapids, Michigan, 49503
Memorial Cancer Institute
Hollywood, Florida, 33021
Research Medical Center
Kansas City, Missouri, 64132
Tennessee Oncology
Nashville, Tennessee, 37203
Nebraska Methodist Cancer Center
Omaha, Nebraska, 68114
Woodlands Medical Specialists
Pensacola, Florida, 32503
Mercy Hospital
Portland, Maine, 04102
Virginia Cancer Institute
Richmond, Virginia, 23230
Florida Cancer Specialists North
St. Petersburg, Florida, 33705
About this study
Official title: A Randomized Phase II Study of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Locally Advanced HER2-Negative Breast Cancer
The investigators propose a randomized phase II study evaluating the pCR and toxicity profiles of combination eribulin/cyclophosphamide (ErC) and docetaxel /cyclophosphamide (TC) as neoadjuvant therapy for locally advanced HER2-negative breast cancer.
- Conditions
- HER2 Negative Breast Cancer
- Being tested
- Eribulin, Cyclophosphamide, Docetaxel
- Keywords
- breast cancer, eribulin, Halaven, taxotere
- 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
1.4 mg/m2 IV (Days 1 \& 8), given short (≤15 minute) IV infusion, per institutional standard
CyclophosphamideDrug
Also called Cytoxan
Cyclophosphamide will be given as an IV infusion (600 mg/m2) on Day 1 of each treatment cycle over approximately 30 minutes, or per institutional standard.
DocetaxelDrug
Also called Taxotere
Patients assigned to Treatment Arm 2 will receive docetaxel 75 mg/m2 IV on Day 1 of each treatment cycle every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Eribulin+Cyclophosphamide (ErC) | Experimental | Eribulin (Er): 1.4mg/m2 IV (Days 1 and 8) given short (≤1.5 minutes) IV infusion, per institutional standard
Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard Receives: Drug: Eribulin; Drug: Cyclophosphamide |
| Docetaxel+Cyclophosphamide (TC) | Experimental | Docetaxel (T): 75 mg/m2 IV (Day 1), given by 1-hour IV infusion
Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard Receives: Drug: Cyclophosphamide; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response (pCR) Rate in Patients Treated With ErC for 6 Cycles Prior to Surgery
One cycle = 21 days. Pathologic CR is defined as the absence of invasive tumor in the breast and lymph node tissue removed at the time of definitive surgery as judged by the local pathologist.
Measured: 18 weeks
Secondary outcomes (3)
The Number of Adverse Events as a Measure of Safety and Tolerability.
Treatment-Related Adverse Events occurring in >= 15% of treated patients
Measured: 43 months
Clinical Response Rate (cRR) of ErC as Neoadjuvant Therapy
Defined as the number of patients with a best response of clinical complete or partial response (cCR or cPR) divided by the number of patients qualified for tumor response analysis per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1 for target lesions and assessed by MRI or CT. Complete Response (CR) defined as disappearance of all target lesions; Partial Response (PR) defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD;
Measured: 43 months
Disease-Free Survival (DFS) at 2 Years
Defined as the percent probability that participants had not experienced disease recurrence or died from any cause at 2 years post-surgery, analyzed by Kaplan-Meier methodology.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2012 (estimated)
- Study startJun 2012
- Primary completionSep 2014
- Study completionJul 2016
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 HER2 Negative 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Eisai Inc.
- Responsible party
- Sponsor
- Investigators
- Denise A Yardley, MD, Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01527487
- Sponsor's protocol ID
- SCRI BRE 197
- Status last verified
- Oct 2016
- First submitted
- 31 Jan 2012
- Last updated
- 4 Nov 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 4 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Locally Advanced HER2-Negative Breast Cancer
- ClinicalTrials.gov ID
- NCT01527487
- Acronym / sponsor ID
- SCRI BRE 197
- Conditions
- HER2 Negative Breast Cancer
- Keywords
- breast cancer, eribulin, Halaven, taxotere
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Eisai Inc.
- Study start
- Jun 2012
- Primary completion
- Sep 2014 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 7 Feb 2012 (estimated)
- Results
- Posted 26 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators propose a randomized phase II study evaluating the pCR and toxicity profiles of combination eribulin/cyclophosphamide (ErC) and docetaxel /cyclophosphamide (TC) as neoadjuvant therapy for locally advanced HER2-negative breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Eribulin+Cyclophosphamide (ErC) | Experimental | Drug: Eribulin, Drug: CyclophosphamideEribulin (Er): 1.4mg/m2 IV (Days 1 and 8) given short (≤1.5 minutes) IV infusion, per institutional standard Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard |
| Docetaxel+Cyclophosphamide (TC) | Experimental | Drug: Cyclophosphamide, Drug: DocetaxelDocetaxel (T): 75 mg/m2 IV (Day 1), given by 1-hour IV infusion Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Histologically confirmed invasive adenocarcinoma of the breast.
- Primary palpable disease confined to the breast and axilla on physical examination (clinical Stage II or III disease). For patients without clinically suspicious axillary adenopathy, the primary must be >2 cm in diameter by physical examination or imaging studies (clinical T2-3, N0-2, M0). For patients with clinically suspicious axillary adenopathy, the primary breast tumor can be any size (clinical T1-3, N1-2, M0). Patients who have had axillary node dissection and have pN3a (i.e. ≥10 involved axillary nodes) are also eligible.
- Patients entering the trial after undergoing an axillary node dissection will be eligible if they meet other entry criteria.
- Estrogen receptor (ER) and progesterone receptor (PR) status in the primary tumor known or pending at the time of study registration.
- Resolution of all acute effects of surgical procedures to ≤ grade 1. For patients who had or will have, a sentinel node and/or axillary node dissection, completion at least 1 week prior to the initiation of study treatment with a well-healed wound is required.
Key exclusion criteria (21 listed)
- Clinical T4 lesions, including inflammatory breast cancer. Clinical N3 involvement (e.g., ipsilateral, infraclavicular, supraclavicular, and internal mammary nodes).
- Peripheral neuropathy (motor or sensory) > grade 1 according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
- Patient has received radiotherapy for treatment of previous cancer that included ≥30% of major bone marrow containing areas (e.g., pelvis, lumbar, spine).
- Known or suspected allergy or hypersensitivity to any of the study drugs (i.e., eribulin, cyclophosphamide, docetaxel) or known hypersensitivity to polysorbate 80.
- Patients with acute or chronic liver or renal disease or pancreatitis.
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: Halaven1.4 mg/m2 IV (Days 1 \& 8), given short (≤15 minute) IV infusion, per institutional standard | Drug | Eribulin+Cyclophosphamide (ErC) |
| CyclophosphamideAlso: CytoxanCyclophosphamide will be given as an IV infusion (600 mg/m2) on Day 1 of each treatment cycle over approximately 30 minutes, or per institutional standard. | Drug | Docetaxel+Cyclophosphamide (TC), Eribulin+Cyclophosphamide (ErC) |
| DocetaxelAlso: TaxoterePatients assigned to Treatment Arm 2 will receive docetaxel 75 mg/m2 IV on Day 1 of each treatment cycle every 3 weeks. | Drug | Docetaxel+Cyclophosphamide (TC) |
Primary outcome
Pathologic Complete Response (pCR) Rate in Patients Treated With ErC for 6 Cycles Prior to Surgery
Time frame: 18 weeks
One cycle = 21 days. Pathologic CR is defined as the absence of invasive tumor in the breast and lymph node tissue removed at the time of definitive surgery as judged by the local pathologist.
3 secondary outcomes
The Number of Adverse Events as a Measure of Safety and Tolerability.
Time frame: 43 months
Clinical Response Rate (cRR) of ErC as Neoadjuvant Therapy
Time frame: 43 months
Disease-Free Survival (DFS) at 2 Years
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 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.
Denise A Yardley, MD study chair
SCRI Development Innovations, LLC
15 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, Cyclophosphamide and Docetaxel in people with HER2 Negative Breast Cancer, run by SCRI Development Innovations, LLC at 15 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 31 inclusion and 21 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 4 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 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 26 Aug 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 (pCR) Rate in Patients Treated With ErC for 6 Cycles Prior to Surgery (time frame: 18 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 4 Nov 2016.