Clinical trial NCT03264547: A Study to Compare Eribulin Mesylate + Pertuzumab + Trastuzumab With Paclitaxel or Docetaxel + Pertuzumab + Trastuzumab
Official title: A Phase III Clinical Study to Compare the Combination Therapy of Eribulin Mesylate + Pertuzumab + Trastuzumab With Paclitaxel or Docetaxel + Pertuzumab + Trastuzumab (EMERALD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Japan Breast Cancer Research Group
Sponsor class: OTHER
Collaborators: name: Eisai Co., Ltd.
First posted: 2017-08-29
Enrollment: 480
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To verify that combination therapy with trastuzumab + pertuzumab + eribulin brings similar PFS and better QOL compared to trastuzumab + pertuzumab + taxane in advanced/recurrent HER2-positive breast cancer patients who have no medical history of chemotherapy except ado-trastuzumab emtansine


Eligibility criteria: Inclusion Criteria:

1. Patients with breast cancer that is confirmed histologically or cytologically
2. Patients who are confirmed to be HER2 positive for the primary or a metastatic lesion at a participating medical institution
3. Patients with no medical history of treatment for advanced/recurrent cancer using a regimen of drugs including chemotherapeutics
4. \>=6 months have passed since perioperative treatment with anticancer agents
5. Presence of a measurable lesion not required
6. Female aged 20-70 years old at the time of consent acquisition
7. Baseline left ventricular ejection fraction (LVEF) measured by ECHO or MUGA of \>=50%
8. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1
9. Patients who have maintained major organ functions, meeting all of the following criteria on a test within 28 days before enrollment. If there are multiple test results during this period, that obtained immediately before enrollment should be adopted.

(1) Neutrophil count: \>=1,500/mm3 (2) Platelet count: \>=100,000/mm 3 (3) Hemoglobin: \>=9.0 g/dL (4) Total bilirubin: \<=1.5 mg/dL (5) AST (GOT), ALT (GPT): \<=2.5 times the ULN (\<=5 times in those with liver metastasis) (6) Serum creatinine: \<=1.5 mg/dL 10) Patients with a life expectancy of at least 6 months 11) Patient who submits written consent herself after receiving sufficient explanation about this study 12) Patients who can undergo QOL investigation

Exclusion Criteria:

1. Patients planning to undergo radical surgery if they respond to a treatment
2. Patients who have non-hematological adverse events assessed as Grade \>=3 in the Common Terminology Criteria for Adverse Events ver. 4.0 in the Japanese JCOG version (CTCAE v4.0-JCOG) at the time of enrollment
3. Patients who have symptomatic metastases to the central nervous system or whose symptoms are hard to control
4. Patients who have active double cancer
5. Patients who have poorly controlled hypertension, or unstable angina
6. Patients who have a past history of congestive heart failure assessed as Class ll or higher in the New York Heart Association (NYHA) classification, or clinically significant arrhythmia requiring treatment
7. Patients with a past history of myocardial infarction within 6 months before enrollment
8. Patients who are expected to undergo major surgical treatment or who had severe injury within 28 days before enrollment, or who require major surgical treatment during the study treatment period
9. Patients with interstitial pneumonia which is symptomatic or requires treatment
10. Pregnant women, those with a positive pregnancy test, and lactating women
11. Patients with active systemic infection (including HCV and HBV), or who are found to be HIV-positive
12. Patients with hypersensitivity against pertuzumab and trastuzumab
13. Patients whom the investigator consider unable or unwilling to follow the protocol requirements

Primary outcomes:
measure: PFS
timeFrame: 5.75 years
Secondary outcomes:
measure: RR
timeFrame: 5.75 years
measure: DR
timeFrame: 5.75 years
measure: OS
timeFrame: 6.25 years
measure: PRO
timeFrame: 5.75 years
measure: Safety
timeFrame: 5.75 years
measure: Biomaker
timeFrame: 5.75 years
measure: nMFS
timeFrame: 5.75 years
measure: TTF of the subsequent treatment
timeFrame: 5.75 years
Other outcomes:
Locations:
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Ōsaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
state: Osaka
Study officials:
affiliation: Kanagawa Cancer Center
name: Toshinari Tamashita, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: NHO Osaka National Hospital
name: Norikazu Masuda, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fukushima Medical University
name: Shigehira Saji, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. doi: 10.1056/NEJMoa1113216. Epub 2011 Dec 7.
citation: 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.
citation: Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, Olivo MS, He Y, Dutcus CE, Cortes J. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015 Feb 20;33(6):594-601. doi: 10.1200/JCO.2013.52.4892. Epub 2015 Jan 20.
citation: Wilks S, Puhalla S, O'Shaughnessy J, Schwartzberg L, Berrak E, Song J, Cox D, Vahdat L. Phase 2, multicenter, single-arm study of eribulin mesylate with trastuzumab as first-line therapy for locally recurrent or metastatic HER2-positive breast cancer. Clin Breast Cancer. 2014 Dec;14(6):405-12. doi: 10.1016/j.clbc.2014.04.004. Epub 2014 Jun 2.
citation: Yamashita T, Masuda N, Saji S, Araki K, Ito Y, Takano T, Takahashi M, Tsurutani J, Koizumi K, Kitada M, Kojima Y, Sagara Y, Tada H, Iwasa T, Kadoya T, Iwatani T, Hasegawa H, Morita S, Ohno S. Trastuzumab, pertuzumab, and eribulin mesylate versus trastuzumab, pertuzumab, and a taxane as a first-line or second-line treatment for HER2-positive, locally advanced or metastatic breast cancer: study protocol for a randomized controlled, non-inferiority, phase III trial in Japan (JBCRG-M06/EMERALD). Trials. 2020 May 7;21(1):391. doi: 10.1186/s13063-020-04341-y.