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

• ClinicalTrials.gov Identifier: NCT01401959
• Recruitment Status: Completed
• First Posted: July 26, 2011
• Results First Posted: May 7, 2018
• Last Update Posted: June 15, 2018
• Sponsor: SCRI Development Innovations, LLC
• Collaborator: Eisai Inc.
• Information provided by (Responsible Party): SCRI Development Innovations, LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Breast Cancer	Drug: Eribulin; Drug: Trastuzumab	Phase 2

Detailed Description:

This is a non-randomized, open-label trial to evaluate 6 cycles of eribulin in female patients with invasive breast cancer who do not achieve pathologic complete response (pCR) after treatment with a standard neoadjuvant chemotherapy and surgery regimen. Patients will be randomized into three cohorts according to tumor-type: triple-negative (Cohort A), hormone-receptor-positive/HER2-negative (Cohort B), and HER2-positive (Cohort C) tumors. Patients will receive eribulin for 6 cycles (1 cycle = 21 days). Patients with HER2-positive tumors will also receive trastuzumab. Patients in all cohorts will be allowed to receive locoregional radiotherapy and/or adjuvant hormonal therapy per institutional guidelines.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 127 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Eribulin in Patients Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy
• Actual Study Start Date: September 23, 2011
• Actual Primary Completion Date: April 3, 2017
• Actual Study Completion Date: April 3, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort A: Triple-negative breast cancer; Eribulin 1.4 mg/m^2 intravenously (IV)	Drug: Eribulin; 1.4 mg/m^2 IV Days 1 and 8, every 21 days for six cycles; Other Name: Halaven
Experimental: Cohort B: ER/PR+ /HER2- breast cancer; Eribulin 1.4 mg/m^2 intravenously (IV)	Drug: Eribulin; 1.4 mg/m^2 IV Days 1 and 8, every 21 days for six cycles; Other Name: Halaven
Experimental: Cohort C: HER2+ breast cancer; Eribulin 1.4 mg/m^2 intravenously (IV) Trastuzumab 6mg/kg intravenously (IV)	Drug: Eribulin; 1.4 mg/m^2 IV Days 1 and 8, every 21 days for six cycles; Other Name: Halaven; Drug: Trastuzumab; 6 mg/kg IV Day 1 every 21 days; Other Name: Herceptin

Outcome Measures

Primary Outcome Measures :

1. Percentage of Patients With a 2 Year Disease-Free Survival (DFS) as a Measure of Efficacy [ Time Frame: Up to 2 years ]
   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.

Secondary Outcome Measures :

1. Number of Patients Who Completed Eribulin Therapy as an Assessment of Treatment Feasibility [ Time Frame: up to 18 weeks ]
   Examines the feasibility of administering 6 cycles (21 days per cycle) of eribulin without toxicity or disease worsening following standard neoadjuvant chemotherapy and surgery.
2. The Number of Participants With Treatment-Related Adverse Events and Serious Adverse Events as a Measure of Safety [ Time Frame: 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. ]
   A treatment-related adverse event or serious adverse event was any untoward medical occurrence in a participant which was considered to have a relationship with the study drug (suspected to be possibly or probably related to the study drug per the Investigator's assessment). Adverse events and serious adverse events will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V4.03.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Female patients >=18 years-of-age.
2. 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.
3. Previous treatment with a minimum of 4 cycles of neoadjuvant anthracycline and/or taxane containing chemotherapy (+trastuzumab in HER2-positive patients).
4. 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.
5. 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].
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
7. 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.
8. Peripheral neuropathy Grade <=2 per NCI CTCAE v4.0 at trial entry.
9. 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).
10. Adequate hematologic, hepatic, and renal function
11. 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.
12. 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.
13. Willingness and ability to comply with trial and follow-up procedures.
14. Ability to understand the investigative nature of this trial and give written informed consent.
15. 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.

Exclusion Criteria:

1. 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.
2. Radiotherapy prior to the start of study treatment.
3. History or clinical evidence of central nervous system metastases or other metastatic disease.
4. Non-healed surgical wound.
5. Known or suspected allergy/hypersensitivity to eribulin.
6. 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.
7. Chronic use of drugs that cause QTc prolongation.Patients must discontinue use of these drugs 7 days prior to the start of study treatment.
8. 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.
9. Patients with known diagnosis of human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.
10. Prolongation of heart rate-corrected QT interval (QTc) >480 msecs (using Bazett's formula).
11. 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.
12. 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.
13. Patients may not receive any other investigational or anti-cancer treatments while participating in this trial.
14. 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.
15. Inability or unwillingness to comply with trial and/or follow-up procedures outlined in the protocol.

Contacts and Locations

Locations

United States, Florida

Florida Cancer Specialists North

Fort Myers, Florida, United States, 33916

Florida Cancer Specialists South

Fort Myers, Florida, United States, 33916

Watson Clinic Center for Cancer Care and Research

Lakeland, Florida, United States, 33805

Florida Hospital Cancer Insitute

Orlando, Florida, United States, 32804

United States, Georgia

Northeast Georgia Medical Center

Gainesville, Georgia, United States, 30501

United States, Indiana

Providence Medical Group

Terre Haute, Indiana, United States, 47802

United States, Maine

Mercy Hospital

Portland, Maine, United States, 04101

United States, Maryland

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States, 20817

National Capital Clinical Research Consortium

Bethesda, Maryland, United States, 20817

United States, Nebraska

Nebraska Methodist Cancer Center

Omaha, Nebraska, United States, 68114

United States, New Jersey

Atlantic Health System

Morristown, New Jersey, United States, 07960

Hematology Oncology Associates of Northern NJ

Morristown, New Jersey, United States, 07960

United States, Ohio

Oncology Hematology Care, Inc.

Cincinnati, Ohio, United States, 45242

United States, South Carolina

South Carolina Oncology Associates

Columbia, South Carolina, United States, 29210

United States, Tennessee

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, United States, 37404

Tennessee Oncology

Nashville, Tennessee, United States, 37203

United States, Texas

Texas Health Physician Group

Arlington, Texas, United States, 76011

The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States, 76104

Sponsors and Collaborators

SCRI Development Innovations, LLC

Eisai Inc.

Investigators

• Study Chair: Denise A Yardley, M.D.; SCRI Development Innovations, LLC

  Study Documents (Full-Text)

Documents provided by SCRI Development Innovations, LLC:

Study Protocol  [PDF] March 20, 2013

Statistical Analysis Plan  [PDF] April 3, 2018

More Information

Publications:

Liedtke C, Mazouni C, Hess KR, André 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.

Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, Chollet P, Manikas A, Diéras 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.

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.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT01401959
• Other Study ID Numbers: SCRI BRE 186
• First Posted: July 26, 2011
• Results First Posted: May 7, 2018
• Last Update Posted: June 15, 2018
• Last Verified: May 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by SCRI Development Innovations, LLC:

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

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Trastuzumab; Antineoplastic Agents, Immunological; Antineoplastic Agents