Clinical Trials /

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

NCT02514681

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: JBCRG-M05
  • NCT ID: NCT02514681

Conditions

  • HER2-positive Locally Advanced or Metastatic Breast Cancer

Interventions

DrugSynonymsArms
TrastuzumabHerceptinTrastuzumab + chemotherapy
PertuzumabPerjetaTrastuzumab+ pertuzumab + chemotherapy
DocetaxelTaxotereTrastuzumab + chemotherapy
PaclitaxelTaxolTrastuzumab + chemotherapy
Nab-paclitaxelAbraxaneTrastuzumab + chemotherapy
VinorelbineNavelbineTrastuzumab + chemotherapy
EribulinHalavenTrastuzumab + chemotherapy
CapecitabineXelodaTrastuzumab + chemotherapy
GemcitabineGemzarTrastuzumab + chemotherapy

Purpose

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
Trastuzumab + chemotherapyActive ComparatorTrastuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel ,Vinorelbine, Eribulin, Capecitabine or Gemcitabine
  • Trastuzumab
  • Docetaxel
  • Paclitaxel
  • Nab-paclitaxel
  • Vinorelbine
  • Eribulin
  • Capecitabine
  • Gemcitabine
Trastuzumab+ pertuzumab + chemotherapyExperimentalTrastuzumab+ pertuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel, Vinorelbine, Eribulin, Capecitabine or Gemcitabine
  • Trastuzumab
  • Pertuzumab
  • Docetaxel
  • Paclitaxel
  • Nab-paclitaxel
  • Vinorelbine
  • Eribulin
  • Capecitabine
  • Gemcitabine

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed invasive breast cancer

          2. 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

          3. 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.

          4. Patients have measurable and/or non-measurable disease according to RECIST ver1.1.

          5. Female patients and aged ≥ 20 years.

          6. Left Ventricular Ejection Fraction (LVEF) > 50% at baseline (within 28 days before
             enrollment) as determined by either ECHO or MUGA

          7. Eastern Cooperative Oncology Group performance status of 0,1 or 2.

          8. Life expectancy of patients is expected at least 3 months.

          9. Signed and written informed consent (approved by the Institutional Review Board or
             Independent Ethics Committee) is obtained before any study procedure.

        Exclusion Criteria:

          1. 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).

          2. Persistent Grade >3 non-hematologic toxicity according to NCI-CTCAE v4.0-JCOG
             resulting from previous therapy at the time of enrollment.

          3. Symptomatic or uncontrolled central nervous system metastases.

          4. Multiple malignancies without history of breast cancer(within 10 years if invasive
             breast cancer and within 5 years if malignancies except invasive breast cancer)

          5. 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.

          6. Current uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg) or
             unstable angina.

          7. History of CHF of any New York Heart Association criteria, or serious cardiac
             arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal
             supraventricular tachycardia).

          8. History of myocardial infarction within 6 months of enrollment.

          9. Dyspnea at rest due to complications of advanced malignancy.

         10. 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

         11. 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.

         12. Uncontrolled malignancy-associated hypercalcemia syndrome under bisphosphonates or
             denosumab treatment.

         13. Radiation related grade >2 adverse event within 14 days before enrollment.

         14. 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.

         15. Pregnant woman or positive pregnancy test.

         16. Nursing woman

         17. History of receiving any investigational treatment within 28 days before enrollment.

         18. Current known and active infection with human immunodeficiency virus, hepatitis B
             virus or hepatitis C virus.

         19. Receipt of intravenous antibiotics for infection within 14 days before enrollment.

         20. Current chronic daily treatment (continuous for > 3 months) with corticosteroids (dose
             equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled
             steroids.

         21. Known hypersensitivity to pertuzumab or trastuzumab without infusion reaction related
             to these drugs

         22. Assessed by the investigator to be unable or unwilling to comply with the requirements
             of the protocol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (assessed by investigators)
Time Frame:4 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression-free survival (assessed by independent review)
Time Frame:4 years
Safety Issue:
Description:
Measure:PFS in patients treated with trastuzumab emtansine (T-DM1) as the latest regimen
Time Frame:4 years
Safety Issue:
Description:
Measure:Response rate
Time Frame:4 years
Safety Issue:
Description:
Measure:Duration of response, Overall survival
Time Frame:4 years
Safety Issue:
Description:
Measure:Patient-reported-outcome
Time Frame:4 years
Safety Issue:
Description: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.
Measure: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.
Time Frame:4 years
Safety Issue:
Description:Safety for HER2-positive locally advanced or metastatic breast cancer subjects who were previously treated with Pertuzumab
Measure:Biomarkers
Time Frame:4 years
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Japan Breast Cancer Research Group

Last Updated

April 18, 2017