Description:
This research study is studying a drug called eribulin combined with standard treatment as a possible preoperative treatment for HER2 negative inflammatory breast cancer.
This research study is studying a drug called eribulin combined with standard treatment as a possible preoperative treatment for HER2 negative inflammatory breast cancer.
Recruiting
Phase 2
NCT ID: NCT02623972
ORG ID: 15-292
Inflammatory Breast Cancer
Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
Drug | Synonyms | Arms |
---|---|---|
Eribulin | Halaven, B1939 mesylate | Eribulin |
Adriamycin | Doxorubicin | Eribulin |
Cyclophosphamide | Cytoxan, Neosar | Eribulin |
This research study is studying a drug called eribulin combined with standard treatment as a
possible preoperative treatment for HER2 negative inflammatory breast cancer.
This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational intervention to learn whether the intervention works
in treating a specific disease. "Investigational" means that the intervention is being
studied..
Eribulin works by interfering with cancer cell division, growth, and spread.
The goal of this research study is to evaluate inflammatory breast cancer's response to
treatment with eribulin followed by AC chemotherapy when given as a preoperative
chemotherapy treatment for participants with HER2 negative inflammatory breast cancer.
Name | Type | Description | Interventions |
---|---|---|---|
Eribulin | Experimental | Eribulin-Administered via iv, at predetermined dosage and schedule per cycle Two research breast biopsies Adriamycin (doxorubicin) via iv a predetermined dosage and schedule per cycle Cyclophosphamide (AC) via iv a predetermined dosage and schedule per cycle Surgical Removal of the breasts (Mastectomy) and axillary lymph node dissection Radiation Therapy Endocrine Therapy (if applicable) Optional 10 Patient-Optional DCE-MRI (Dynamic Contrast Enhanced-Magnetic Resonance Imaging) scans | Eribulin, Adriamycin, Cyclophosphamide |
Inclusion Criteria:
- Participants must have histologically confirmed invasive breast cancer. All
histologic subtypes are eligible.
-- Patients must have known HER2 status defined as negative (defined as IHC 0 or 1+,
or FISH ratio <2.0). Any ER or PR status is allowed.
- Age 18 years. Because no dosing or adverse event data are currently available on the
use of eribulin in participants <18 years of age, children are excluded from this
study
- ECOG performance status 1 (Karnofsky 70%, see Appendix A)
- Participants must have normal organ and marrow function as defined below:
- leukocytes 3,000/mcL
- absolute neutrophil count 1,500/mcL
- platelets 100,000/mcL
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) 2.5 institutional upper limit of normal creatinine within
normal institutional limits
--- OR
- creatinine clearance 60 mL/min/1.73 m2 for participants with creatinine levels
above institutional normal.
- Patients must have the clinical diagnosis of inflammatory breast cancer as evidenced
by the onset of signs and symptoms noted below within a 6 month time-period:
- Erythema of the breast
- Edema of the skin of the breast
- Enlargement of the breast
- Patients must be without evidence of visceral or bone involvement with metastatic
cancer on physical exam or any diagnostic study. Extensive nodal involvement is
allowed.
- LVEF > 50% calculated by echocardiogram (ECHO)
- Patients may have bilateral breast cancer so long as one breast meets criteria for
inflammatory breast cancer, and neither breast cancer has received prior therapy.
- The effects of eribulin on the developing human fetus are unknown. For this reason
and because other therapeutic agents used in this trial are known to be teratogenic,
women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation. Should a woman become pregnant or suspect
she is pregnant while she or her partner is participating in this study, she should
inform her treating physician immediately. Men treated or enrolled on this protocol
must also agree to use adequate contraception prior to the study, for the duration of
study participation, and 4 months after completion of eribulin administration.
- Ability to understand and the willingness to sign a written informed consent
document.
- Both men and women of all races and ethnic groups are eligible for this trial.
Because breast cancer predominantly affects females, it is anticipated that male
enrollment will be < 5% of the overall study population.
Exclusion Criteria:
- Participants who are receiving any other investigational agents.
- Participants with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
events.
- Patients with evidence of metastatic disease involvement in viscera or bone.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to eribulin or other agents used in study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.
- Pregnant women are excluded from this study because eribulin is an agent with the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with eribulin, breastfeeding should be discontinued if the mother is treated
with eribulin. These potential risks may also apply to other agents used in this
study.
- HIV-positive participants on combination antiretroviral therapy are ineligible
because of the potential for pharmacokinetic interactions with eribulin. In addition,
these participants are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in participants
receiving combination antiretroviral therapy when indicated.
- A baseline corrected QT interval of > 470 ms.
- Individuals with a history of a different malignancy are ineligible except for the
following circumstances. Individuals with a history of other malignancies are
eligible if they have been disease-free for at least 3 years and are deemed by the
investigator to be at low risk for recurrence of that malignancy. Individuals with
the following cancers are eligible if diagnosed and treated within the past 3 years:
cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
- Patients may not have received paclitaxel, doxorubicin, or cyclophosphamide as
anti-neoplastic therapy.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Pathologic Complete Response
Disease Free Survival
Time to Treatment Failure
Overall Survival
Pathologic disease response at mastectomy will be reported as "residual disease burden (RCB)".
RT-qPCR assessment of gene expression of 10-EMT-related genes and 15-genes involved in modulating vessel phenotype or EC-PVC interactions will be compared following treatment with eribulin.
To correlate changes in imaging (Ktrans ve, vp, and initial area under the curve (iAUC)) with genomic changes determined on core biopsies of the breast sampled at the same time points.
inflammatory breast cancer
Human Epidermal Growth Factor 2 Negative Carcinoma of Breast