Trial of Eribulin in Patients Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy

NCT01401959 | Completed Phase 2 Results FDA Drug

• 1 other identifier: SCRI BRE 186
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 18

Brief Summary

The investigators propose to evaluate eribulin as adjuvant therapy in breast cancer patients who have residual invasive disease in breast or lymph node tissue following standard neoadjuvant chemotherapy and surgery regimen. Three cohorts of patients will be evaluated separately based on tumor type: triple-negative, hormone-receptor-positive/HER2-negative, and HER2-positive breast cancers.

Conditions

Metastatic Breast Cancer

Keywords

Metastatic Breast Cancer; Adjuvant; Residual Disease; eribulin; Trastuzumab

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With a 2 Year Disease-Free Survival (DFS) as a Measure of Efficacy

  The percentage of patients that are without evidence of disease recurrence at the 2 year timepoint, as measured from date of first protocol treatment date to first documented disease progression date or date of death from any cause, whichever comes first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Up to 2 years

Secondary Outcomes (2)

• Number of Patients Who Completed Eribulin Therapy as an Assessment of Treatment Feasibility

  up to 18 weeks

• The Number of Participants With Treatment-Related Adverse Events and Serious Adverse Events as a Measure of Safety

  Weekly during each 21 day cycle and for 30 days after completion of protocol-specific treatment. After that patients were followed every 3 months for up to 2 years.

Study Arms (3)

Cohort A: Triple-negative breast cancer

EXPERIMENTAL

Eribulin 1.4 mg/m\^2 intravenously (IV)

Drug: Eribulin

Cohort B: ER/PR+ /HER2- breast cancer

EXPERIMENTAL

Eribulin 1.4 mg/m\^2 intravenously (IV)

Drug: Eribulin

Cohort C: HER2+ breast cancer

EXPERIMENTAL

Eribulin 1.4 mg/m\^2 intravenously (IV) Trastuzumab 6mg/kg intravenously (IV)

Drug: Eribulin; Drug: Trastuzumab

Interventions

Eribulin DRUG

1.4 mg/m\^2 IV Days 1 and 8, every 21 days for six cycles

Also known as: Halaven

Cohort A: Triple-negative breast cancer; Cohort B: ER/PR+ /HER2- breast cancer; Cohort C: HER2+ breast cancer

Trastuzumab DRUG

6 mg/kg IV Day 1 every 21 days

Also known as: Herceptin

Cohort C: HER2+ breast cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients \>=18 years-of-age.
• Histologically confirmed breast cancer prior to surgery with the following staging criteria: T1-T3, T4a, T4b, N0-N2, N3a and M0 (T1N0M0 patients are excluded). Inflammatory disease is excluded.
• Previous treatment with a minimum of 4 cycles of neoadjuvant anthracycline and/or taxane containing chemotherapy (+trastuzumab in HER2-positive patients).
• Patients must be ≥ 21 days and ≤ 84 days from breast surgery and fully recovered. Patients may have had mastectomy or breast conservation surgery with axillary node dissection.
• Pathologic CR (pCR) not achieved following neoadjuvant treatment (i.e., residual invasive breast cancer (\>5 mm) in the breast or presence of nodal disease at surgery \[ypT0/T1a, N1-N3a, M0 or ypT1b-T4, N0-N3a, M0\].
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
• Recovery from any toxic effects of prior therapy to \<=Grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.0) except fatigue or alopecia.
• Peripheral neuropathy Grade \<=2 per NCI CTCAE v4.0 at trial entry.
• Normal left ventricular ejection fraction (LVEF), within the institutional limits of normal, as measured by echocardiography (ECHO) or multi-gated (MUGA) scan in patients to receive trastuzumab with eribulin (HER2-positive).
• Adequate hematologic, hepatic, and renal function
• Complete staging work-up to confirm localized disease should include computed tomography (CT) scans of the chest and abdomen/pelvis (abdomen/pelvis preferred; abdomen accepted), a CT scan of the head or MRI of the brain (if symptomatic), and either a positron emission tomography (PET) scan or a bone scan. (Note: a PET/CT is acceptable for baseline imaging in lieu of CT examinations or bone scan). Negative scans performed prior to the initiation of neoadjuvant therapy, or at any subsequent time, are acceptable and do not need to be repeated.
• Female patients who are not of child-bearing potential and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum pregnancy test performed within 7 days prior to start of trial treatment.
• Willingness and ability to comply with trial and follow-up procedures.
• Ability to understand the investigative nature of this trial and give written informed consent.
• Agree to delay in reconstruction in terms of implants placed in setting of expanders until chemotherapy is completed and the patient has recovered. Expansion of expanders may continue during trial treatment.

You may not qualify if:

• Presence of other active cancers, or history of treatment for invasive cancer \<3 years prior to trial entry (except thyroid, cervical cancer). 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.
• Radiotherapy prior to the start of study treatment.
• History or clinical evidence of central nervous system metastases or other metastatic disease.
• Non-healed surgical wound.
• Known or suspected allergy/hypersensitivity to eribulin.
• Cardiac disease, including: congestive heart failure Class II-IV per New York Heart Association classification;cardiac ventricular arrhythmias requiring anti-arrhythmic therapy; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months.
• Chronic use of drugs that cause QTc prolongation.Patients must discontinue use of these drugs 7 days prior to the start of study treatment.
• Women who are pregnant or lactating. All females of child-bearing potential must have negative serum pregnancy test within 48 hours prior to trial treatment.
• Patients with known diagnosis of human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.
• Prolongation of heart rate-corrected QT interval (QTc) \>480 msecs (using Bazett's formula).
• Minor surgical procedures (with the exception of the placement of port-a-cath or other central venous access) performed less than 7 days prior to beginning protocol treatment.
• History of cerebrovascular accident including transient ischemic attack (TIA), or untreated deep venous thrombosis (DVT)/ pulmonary embolism (PE) within the past 6 months. Note: Patients with recent DVT/PE receiving treatment with a stable dose of therapeutic anti-coagulating agents are eligible.
• Patients may not receive any other investigational or anti-cancer treatments while participating in this trial.
• History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the trial participation or investigational product(s) administration or may interfere with the interpretation of the results.
• Inability or unwillingness to comply with trial and/or follow-up procedures outlined in the protocol.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Eisai Inc.: collaborator

Study Sites (18)

Florida Cancer Specialists North

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists South

Fort Myers, Florida, 33916, United States

Location

Watson Clinic Center for Cancer Care and Research

Lakeland, Florida, 33805, United States

Location

Florida Hospital Cancer Insitute

Orlando, Florida, 32804, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Providence Medical Group

Terre Haute, Indiana, 47802, United States

Location

Mercy Hospital

Portland, Maine, 04101, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

National Capital Clinical Research Consortium

Bethesda, Maryland, 20817, United States

Location

Nebraska Methodist Cancer Center

Omaha, Nebraska, 68114, United States

Location

Atlantic Health System

Morristown, New Jersey, 07960, United States

Location

Hematology Oncology Associates of Northern NJ

Morristown, New Jersey, 07960, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45242, United States

Location

South Carolina Oncology Associates

Columbia, South Carolina, 29210, United States

Location

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Texas Health Physician Group

Arlington, Texas, 76011, United States

Location

The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

Related Publications (3)

• Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, Cristofanilli M, Hortobagyi GN, Pusztai L. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008 Mar 10;26(8):1275-81. doi: 10.1200/JCO.2007.14.4147. Epub 2008 Feb 4.

  PMID: 18250347 BACKGROUND

• Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, Chollet P, Manikas A, Dieras V, Delozier T, Vladimirov V, Cardoso F, Koh H, Bougnoux P, Dutcus CE, Seegobin S, Mir D, Meneses N, Wanders J, Twelves C; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011 Mar 12;377(9769):914-23. doi: 10.1016/S0140-6736(11)60070-6. Epub 2011 Mar 2.

  PMID: 21376385 BACKGROUND

• Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, Welsh S, Zheng W, Seletsky BM, Palme MH, Habgood GJ, Singer LA, Dipietro LV, Wang Y, Chen JJ, Quincy DA, Davis A, Yoshimatsu K, Kishi Y, Yu MJ, Littlefield BA. In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res. 2001 Feb 1;61(3):1013-21.

  PMID: 11221827 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm, Residual

Interventions

eribulin; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Senior Director, Regulatory Science
• Organization: Sarah Cannon Development Innovations

CANN.InnovationsMedical@sarahcannon.com

844-710-6157

Study Officials

• Denise A Yardley, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2011
• First Posted: July 26, 2011
• Study Start: September 23, 2011
• Primary Completion: April 3, 2017
• Study Completion: April 3, 2017
• Last Updated: June 15, 2018
• Results First Posted: May 7, 2018

Record last verified: 2018-05

Locations

US (18)