A Phase III Trial of Pertuzumab Retreatment in Previously Pertuzumab Treated Her2-Positive Advanced Breast Cancer

NCT02514681 | Completed Phase 3

• 1 other identifier: JBCRG-M05
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of pertuzumab, trastuzumab and chemotherapy as a pertuzumab retreatment compared to trastuzumab and chemotherapy in locally advanced or metastatic breast cancer patients for previously treated with pertuzumab

Conditions

HER2-positive Locally Advanced or Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (assessed by investigators)

  4 years

Secondary Outcomes (7)

• Progression-free survival (assessed by independent review)

  4 years

• PFS in patients treated with trastuzumab emtansine (T-DM1) as the latest regimen

  4 years

• Response rate

  4 years

• Duration of response, Overall survival

  4 years

• Patient-reported-outcome

  4 years

Study Arms (2)

Trastuzumab + chemotherapy

ACTIVE COMPARATOR

Trastuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel ,Vinorelbine, Eribulin, Capecitabine or Gemcitabine

Drug: Trastuzumab; Drug: Docetaxel; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Vinorelbine; Drug: Eribulin; Drug: Capecitabine; Drug: Gemcitabine

Trastuzumab+ pertuzumab + chemotherapy

EXPERIMENTAL

Trastuzumab+ pertuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel, Vinorelbine, Eribulin, Capecitabine or Gemcitabine

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Docetaxel; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Vinorelbine; Drug: Eribulin; Drug: Capecitabine; Drug: Gemcitabine

Interventions

Trastuzumab DRUG

Also known as: Herceptin

Trastuzumab + chemotherapy; Trastuzumab+ pertuzumab + chemotherapy

Pertuzumab DRUG

Also known as: Perjeta

Trastuzumab+ pertuzumab + chemotherapy

Docetaxel DRUG

Also known as: Taxotere

Trastuzumab + chemotherapy; Trastuzumab+ pertuzumab + chemotherapy

Paclitaxel DRUG

Also known as: Taxol

Trastuzumab + chemotherapy; Trastuzumab+ pertuzumab + chemotherapy

Nab-paclitaxel DRUG

Also known as: Abraxane

Trastuzumab + chemotherapy; Trastuzumab+ pertuzumab + chemotherapy

Vinorelbine DRUG

Also known as: Navelbine

Trastuzumab + chemotherapy; Trastuzumab+ pertuzumab + chemotherapy

Eribulin DRUG

Also known as: Halaven

Trastuzumab + chemotherapy; Trastuzumab+ pertuzumab + chemotherapy

Capecitabine DRUG

Also known as: Xeloda

Trastuzumab + chemotherapy; Trastuzumab+ pertuzumab + chemotherapy

Gemcitabine DRUG

Also known as: Gemzar

Trastuzumab + chemotherapy; Trastuzumab+ pertuzumab + chemotherapy

Eligibility Criteria

• Age: 20 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed invasive breast cancer
• A confirmed HER2-positive status assessed by means of immunohistochemical analysis (with 3+ indicating positive status) and/or in situ hybridization (with an amplification ratio \> 2.0 indicating positive) by each institute
• History of pertuzumab and trastuzumab-containing chemotherapy for locally advanced and metastatic breast cancer(2 or 3 regimen as previous chemotherapy regimen for locally advanced or metastatic breast cancer). The latest regimen before enrollment dose not include pertuzumab.
• Patients have measurable and/or non-measurable disease according to RECIST ver1.1.
• Female patients and aged ≥ 20 years.
• Left Ventricular Ejection Fraction (LVEF) \> 50% at baseline (within 28 days before enrollment) as determined by either ECHO or MUGA
• Eastern Cooperative Oncology Group performance status of 0,1 or 2.
• Life expectancy of patients is expected at least 3 months.
• Signed and written informed consent (approved by the Institutional Review Board or Independent Ethics Committee) is obtained before any study procedure.

You may not qualify if:

• History of chemotherapy \> 4 regimen for locally advance or metastatic disease except for cancer chemotherapeutic agent-free treatment regimen (eg, hormonal therapy alone, combination with hormonal therapy and trastuzumab and anti-HER2 therapy alone).
• Persistent Grade \>3 non-hematologic toxicity according to NCI-CTCAE v4.0-JCOG resulting from previous therapy at the time of enrollment.
• Symptomatic or uncontrolled central nervous system metastases.
• Multiple malignancies without history of breast cancer(within 10 years if invasive breast cancer and within 5 years if malignancies except invasive breast cancer)
• History of exposure to the following cumulative doses of anthracyclines:
• doxorubicin or liposomal doxorubicin \> 360 mg/m2
• epirubicin \> 720 mg/m2
• mitoxantrone \> 100 mg/m2
• If more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin.
• Current uncontrolled hypertension (systolic \> 150 mmHg and/or diastolic \> 100 mmHg) or unstable angina.
• History of CHF of any New York Heart Association criteria, or serious cardiac arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal supraventricular tachycardia).
• History of myocardial infarction within 6 months of enrollment.
• Dyspnea at rest due to complications of advanced malignancy.
• Inadequate organ function, as determined by the following laboratory results, within 28 days before enrollment:
• Absolute neutrophil count \< 1,500/mm3

Sponsors & Collaborators

• Japan Breast Cancer Research Group: lead
• Chugai Pharmaceutical: collaborator

Study Sites (3)

Aichi Cancer Center

Chikusa-ku, Aichi-ken, 4648681, Japan

Location

Kumamoto University Hospital

Kumamoto, Kumamoto, 8608556, Japan

Location

Japan Breast Cancer Research Group

Chuo-ku, Nihonbashi, Koami-cho, Tokyo, 1030016, Japan

Location

Related Publications (5)

• Lee-Hoeflich ST, Crocker L, Yao E, Pham T, Munroe X, Hoeflich KP, Sliwkowski MX, Stern HM. A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res. 2008 Jul 15;68(14):5878-87. doi: 10.1158/0008-5472.CAN-08-0380.

  PMID: 18632642 BACKGROUND

• 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.

  PMID: 22149875 BACKGROUND

• Giordano SH, Temin S, Kirshner JJ, Chandarlapaty S, Crews JR, Davidson NE, Esteva FJ, Gonzalez-Angulo AM, Krop I, Levinson J, Lin NU, Modi S, Patt DA, Perez EA, Perlmutter J, Ramakrishna N, Winer EP; American Society of Clinical Oncology. Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014 Jul 1;32(19):2078-99. doi: 10.1200/JCO.2013.54.0948. Epub 2014 May 5.

  PMID: 24799465 BACKGROUND

• Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study. J Clin Oncol. 2017 Jan 10;35(2):141-148. doi: 10.1200/JCO.2016.67.4887. Epub 2016 Nov 7.

  PMID: 28056202 BACKGROUND

• Yamamoto Y, Iwata H, Saji S, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Taira N, Morita S, Toi M, Ohno S, Masuda N. Pertuzumab Retreatment for Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced/Metastatic Breast Cancer (PRECIOUS Study): Final Overall Survival Analysis. J Clin Oncol. 2025 May 10;43(14):1631-1637. doi: 10.1200/JCO-24-01673. Epub 2025 Jan 24.

  PMID: 39854662 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; pertuzumab; Docetaxel; Paclitaxel; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Vinorelbine; eribulin; Capecitabine; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Hiroji Iwata, MD, PhD

  Aichi Cancer Center Hospital

  PRINCIPAL INVESTIGATOR

• Yutaka Yamamoto, MD, PhD

  Kumamoto University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2015
• First Posted: August 4, 2015
• Study Start: August 1, 2015
• Primary Completion: December 31, 2018
• Study Completion: August 10, 2022
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

JP (3)