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HER2-positive Locally Advanced or Metastatic Breast CancerPhase 3PRECIOUSNCT02514681

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

A Phase 3 study testing Trastuzumab, Pertuzumab and Docetaxel in people with HER2-positive Locally Advanced or Metastatic Breast Cancer, run by Japan Breast Cancer Research Group at 3 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 20 years and older, women only
What is being tested?
Trastuzumab, Pertuzumab and Docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
226 participants
Where
3 sitesJapan
Study dates
1 Aug 2015to 10 Aug 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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
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  • 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
  • Platelet count < 100,000/mm3
  • Hemoglobin < 8.0 g/dL
  • Total bilirubin > 2.0 mg/dL, unless the patient has documented Gilbert's syndrome
  • Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 100IU /L with the following exception (If considered that the liver dysfunction due to liver metastases > 200 IU/L, or 100 < , ≤200 IU/L with serum albumin < 2.5 g/dL)
  • Serum creatinine value > 2.0 mg/dL or 177 μmol/L
  • Current severe uncontrolled systemic disease(eg. Clinically significant cardiovascular, pulmonary and metabolic disease*, disorder of wound healing, ulcer and fracture)
  • If gemcitabine is planned to be selected as a combination chemotherapeutic agent,patients who has symptomatic interstitial pneumonia or pulmonary fibrosis on chest X-ray should be excluded.
  • Uncontrolled malignancy-associated hypercalcemia syndrome under bisphosphonates or denosumab treatment.
  • Radiation related grade >2 adverse event within 14 days before enrollment.
  • Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of need for major surgery during the course of study treatment.
  • Pregnant woman or positive pregnancy test.
  • Nursing woman
  • History of receiving any investigational treatment within 28 days before enrollment.
  • Current known and active infection with human immunodeficiency virus, hepatitis B virus or hepatitis C virus.
  • Receipt of intravenous antibiotics for infection within 14 days before enrollment.
  • Current chronic daily treatment (continuous for > 3 months) with corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids.
  • Known hypersensitivity to pertuzumab or trastuzumab without infusion reaction related to these drugs
  • Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Trial locations and contacts

3 sites in 1 country.

Japan3 sites

  • Aichi Cancer Center

    Chikusa-ku, Aichi-ken, 4648681

  • Japan Breast Cancer Research Group

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

  • Kumamoto University Hospital

    Kumamoto, Kumamoto, 8608556

Other trials in Japan

About this study

Official title: A Randomized, Open-label Phase III Trial to Evaluate the Efficacy and Safety of Pertuzumab Retreatment in Previously Pertuzumab, Trastuzuamb and Chemotherapy Treated Her2-Positive Metastatic Advanced Breast Cancer

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

Read the detailed description

The American Society of Clinical Oncology (ASCO) Clinical Practice Guidelines recommend the use of pertuzumab, trastuzumab and taxane as first-line treatment for patients with MBC. As a second-line treatment, trastuzumab emtansine (T-DM1) is also recommended. After a pertuzumab-containing regimen and T-DM1, other HER2-targeted therapeutic regimens, including lapatinib-containing regimens and trastuzumab plus chemotherapy, are recommended as third-line treatments and beyond. However, continual pertuzumab use for progression after a pertuzumab-containing regimen and retreatment with pertuzumab are unclear based on evidence.

The efficacy and the safety of two distinct modalities of a trastuzumab plus pertuzumab-containing regimen after pertuzumab use should be assessed in MBC: continual treatment and retreatment. However, it is clinically difficult to examine the efficacy of continual treatment with a trastuzumab plus pertuzumab-containing regimen because of several circumstances including the results of the MARIANNE study.

In addition, it is also important to evaluate the usefulness of retreatment with a pertuzumab-containing regimen. Continual pertuzumab treatment for progression after pertuzumab treatment is not same as pertuzumab retreatment. HER2-HER3-signaling suppressed by pertuzumab-containing regimens could potentially be restored by anti-HER2 therapy without pertuzumab. Pertuzumab retreatment could potentially re-suppress HER2-HER3-signaling. Therefore, Pertuzumab retreatment can be more effective than trastuzumab-containing treatment without pertuzumab.

Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02514681
Study groupRoleWhat they receive
Trastuzumab + chemotherapyActive comparatorTrastuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel ,Vinorelbine, Eribulin, Capecitabine or Gemcitabine
Receives: Drug: Trastuzumab; Drug: Docetaxel; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Vinorelbine; Drug: Eribulin; Drug: Capecitabine; Drug: Gemcitabine
Trastuzumab+ pertuzumab + chemotherapyExperimentalTrastuzumab+ pertuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel, Vinorelbine, Eribulin, Capecitabine or Gemcitabine
Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Docetaxel; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Vinorelbine; Drug: Eribulin; Drug: Capecitabine; Drug: Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (assessed by investigators)

    Measured: 4 years

Secondary outcomes (7)

  1. Progression-free survival (assessed by independent review)

    Measured: 4 years

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

    Measured: 4 years

  3. Response rate

    Measured: 4 years

  4. Duration of response, Overall survival

    Measured: 4 years

  5. Patient-reported-outcome

    Difference in terms of patient-reported outcome (PRO) between standard group and Pertuzumab treated group FACT-G, FACT-B and EQ-5D are used as assessment tools for PRO.

    Measured: 4 years

  6. Safety assessed by Incidence/Grade of Serious Adverse Events (SAEs), Pertuzumab-specific adverse events, laboratory abnormalities Percentage and number of subjects who discontinued for adverse event.

    Safety for HER2-positive locally advanced or metastatic breast cancer subjects who were previously treated with Pertuzumab

    Measured: 4 years

  7. Biomarkers

    To find Prognostic and predictive biomarker markers for patients receiving anti-HER2 treatment. Changes in immunologic markers on peripheral blood mononuclear cells determined by flow cytometry after anti-HER2 treatment Changes in tumor-derived gene mutations (e.g. PIK3CA, APOBEC3, CDH1…etc.) in ctDNA after anti-HER2 therapy Changes in proteins (e.g. HER2, HER3…etc.) and micro RNAs expression in extracellular vesicle after anti-HER2 therapy Changes in glycans and proteins expression in the plasma after anti-HER2 therapy.

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2015 (estimated)
  2. Study start1 Aug 2015
  3. Primary completion31 Dec 2018
  4. Study completion10 Aug 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
226 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02514681
Sponsor's protocol ID
JBCRG-M05
Acronym
PRECIOUS
Status last verified
Sep 2025
First submitted
28 Jul 2015
Last updated
10 Sep 2025
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 18632642

  • 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.

    PubMed 22149875

  • 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.

    PubMed 24799465

  • 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.

    PubMed 28056202

  • 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.

    PubMed 39854662

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Trastuzumab, Pertuzumab and Docetaxel in people with HER2-positive Locally Advanced or Metastatic Breast Cancer, run by Japan Breast Cancer Research Group at 3 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (assessed by investigators) (time frame: 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02514681, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2025.

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