Clinical Trials /

Phase 2 Study of Standard Chemotherapy With Trastuzumab, Plus or Minus Pertuzumab, for Pre-treated Metastatic Breast Cancer

NCT02229149

Description:

This randomized phase 2 study will seek to determine the effectiveness of chemotherapy (physician's choice of vinorelbine, taxane [paclitaxel, docetaxel or nab paclitaxel] or capecitabine) plus trastuzumab vs chemotherapy (physician's choice) plus trastuzumab plus pertuzumab in women with HER2-overexpressing metastatic breast (MBC) that has been previously treated with ado-trastuzumab emtansine (T-DM1) in the metastatic setting.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Study of Standard Chemotherapy With Trastuzumab, Plus or Minus Pertuzumab, for Pre-treated Metastatic Breast Cancer
  • Official Title: Randomized Phase II Trial of Chemotherapy of Physician's Choice Plus Trastuzumab Versus Chemotherapy of Physician's Choice Plus Trastuzumab Plus Pertuzumab In Women With Pretreated, HER2-Overexpressing Metastatic Breast Cancer (MBC)

Clinical Trial IDs

  • ORG STUDY ID: 13011
  • SECONDARY ID: ML29212
  • NCT ID: NCT02229149

Conditions

  • Breast Neoplasms
  • Malignant Tumor of the Breast

Interventions

DrugSynonymsArms
TrastuzumabHerclon, HerceptinTriple Therapy
Pertuzumab2C4, Perjeta, OmnitargTriple Therapy
Vinorelbine, Paclitaxel, Nab-Paclitaxel , Docetaxel, CapecitabineNavelbine, Abraxane, Taxol, Taxotere, Docecad, XelodaTriple Therapy

Purpose

This randomized phase 2 study will seek to determine the effectiveness of chemotherapy (physician's choice of vinorelbine, taxane [paclitaxel, docetaxel or nab paclitaxel] or capecitabine) plus trastuzumab vs chemotherapy (physician's choice) plus trastuzumab plus pertuzumab in women with HER2-overexpressing metastatic breast (MBC) that has been previously treated with ado-trastuzumab emtansine (T-DM1) in the metastatic setting.

Detailed Description

      The current preferred first-line therapy for patients with HER2-overexpressing metastatic
      breast cancer (MBC) is a taxane plus trastuzumab plus pertuzumab, based on results from the
      CLEOPATRA trial. For patients with disease that has progressed on trastuzumab and a taxane,
      ado-trastuzumab emtansine (T-DM1) was recently approved based on results from the EMILIA
      trial showing superiority in this setting compared with capecitabine plus lapatinib. However,
      the standard for first-line therapy may change again in the near future, when results become
      available from the MARIANNE trial, which is evaluating T-DM1 alone or in combination with
      pertuzumab as upfront therapy. Two important questions that may be raised by the findings of
      this study are whether pertuzumab is effective as second- or later-line therapy following
      single-agent T-DM1, and whether pertuzumab administered beyond progression on prior
      pertuzumab therapy is of clinical benefit as trastuzumab has been proven to be.

      The study will seek to determine the efficacy of chemotherapy (physician's choice of
      vinorelbine, taxane [paclitaxel, docetaxel or nab paclitaxel] or capecitabine) plus
      trastuzumab vs chemotherapy (physician's choice) plus trastuzumab plus pertuzumab in women
      with HER2-overexpressing MBC that has been previously treated with T-DM1 in the metastatic
      setting.

      We hypothesize that the addition of pertuzumab to trastuzumab plus chemotherapy will improve
      median progression-free survival (PFS), compared to trastuzumab plus chemotherapy alone, as
      second- or later-line therapy in patients who have received prior T-DM1. Patients will be
      stratified according to whether they have received prior pertuzumab versus not. We will also
      explore whether continuing treatment with pertuzumab in patients who have been previously
      treated with pertuzumab improves PFS.
    

Trial Arms

NameTypeDescriptionInterventions
Triple TherapyExperimentalPhysician's choice of chemotherapy plus trastuzumab plus pertuzumab trastuzumab, given as a loading dose of 8 mg/kg intravenously (IV, or through the vein) on Day 1 followed by 6 mg/kg IV every 3 weeks thereafter, AND physician's choice of chemotherapy: Vinorelbine 25 mg/m2 IV weekly times 3 with 1 week off; OR Paclitaxel 80 mg/m2 IV weekly times 3 with 1 week off; OR Nab-Paclitaxel 100 mg/m2 IV weekly times 3 with 1 week off; OR Docetaxel 75 mg/m2 IV every 3 weeks; OR Capecitabine 1500 mg by mouth twice a day (PO BID) 14 days on and then 7 days off. AND pertuzumab given as a loading dose of 840 mg IV on Day 1 followed by 420 mg IV every 3 weeks.
  • Trastuzumab
  • Pertuzumab
  • Vinorelbine, Paclitaxel, Nab-Paclitaxel , Docetaxel, Capecitabine
Double TherapyActive ComparatorPhysician's choice of chemotherapy plus trastuzumab trastuzumab, given as a loading dose of 8 mg/kg intravenously (IV, or through the vein) on Day 1 followed by 6 mg/kg IV every 3 weeks thereafter, AND physician's choice of chemotherapy: Vinorelbine 25 mg/m2 IV weekly times 3 with 1 week off; OR Paclitaxel 80 mg/m2 IV weekly times 3 with 1 week off; OR Nab-Paclitaxel 100 mg/m2 IV weekly times 3 with 1 week off; OR Docetaxel 75 mg/m2 IV every 3 weeks; OR Capecitabine 1500 mg PO BID 14 days on and then 7 days off.
  • Trastuzumab
  • Vinorelbine, Paclitaxel, Nab-Paclitaxel , Docetaxel, Capecitabine

Eligibility Criteria

        Inclusion Criteria:

          1. Female, Age ≥ 18 years

          2. Histologic or cytologic confirmation of human epidermal growth factor receptor 2
             (HER2)-positive breast cancer according to most recent biopsy (local testing
             permitted)

          3. Measurable or evaluable metastatic disease by Response Evaluation Criteria in Solid
             Tumors (RECIST) (v1.1)

          4. Previous treatment with ado-trastuzumab emtansine (T-DM1) for metastatic disease

             a. Prior therapy with pertuzumab is allowed but not required

          5. At least 1 but no more than 3 prior chemotherapy regimens for metastatic breast cancer
             (MBC)

          6. Life expectancy > 6 months

          7. Eastern Cooperative Group (ECOG) performance status ≤ 2

          8. Left Ventricular Ejection Fraction (LVEF) ≥ 50% at baseline as determined by either
             echocardiogram (ECHO) or Multi Gated Acquisition Scan (MUGA) and within normal limits
             per institutional guidelines

          9. Adequate bone marrow function as indicated by the following:

               1. Absolute Neutrophil Count (ANC) ≥1500/uL (or 1500 per microliter)

               2. Platelets ≥100,000/uL

               3. Hemoglobin >9 g/dL

         10. Adequate renal function, as indicated by creatinine <1.5 times upper limit of normal
             (ULN)

         11. Adequate liver function, as indicated by bilirubin <1.5 times ULN

         12. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) <2 x ULN unless
             liver metastases are present in which case AST and ALT up to 5.x ULN are allowed

         13. Negative serum pregnancy test within 72 hours before starting study medications for
             women of childbearing potential

         14. Women of childbearing potential must be willing to use an acceptable form of birth
             control (ie, intra-uterine device, diaphragm with spermicide, condom with spermicide,
             or abstinence) for the duration of the study Note: Women are considered postmenopausal
             and not of childbearing potential if they have had 12 months of natural (spontaneous)
             amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of
             vasomotor symptoms), or if they have undergone surgical sterilization.

         15. Signed informed consent obtained prior to any screening procedures.

        Exclusion Criteria:

        Patients will be excluded from the study based on the following criteria:

          1. Prior treatment in the metastatic setting with the agent chosen as physician's choice
             of chemotherapy

          2. Active infection

          3. Uncontrolled central nervous system metastases, defined as clinical or radiologic
             evidence of progression of brain metastases or clinical signs of leptomeningeal
             disease

             a. Patients with treated brain metastases are eligible provided they do not have
             clinical or radiologic evidence of disease progression and have been off of
             dexamethasone for at least 3 weeks

          4. Patient is pregnant or lactating

          5. Prior chemotherapy within the last 3 weeks (last 6 weeks for nitrosureas/mitomycin)

          6. Prior radiation therapy within the last 2 weeks; prior radiation therapy to indicator
             lesion (unless objective disease recurrence or progression within the radiation portal
             has been documented since completion of radiation).

          7. Requirement for chronic steroid therapy with a requirement for > 5mg/day of prednisone
             or the equivalent.

             a. Treatment with physiologic doses of hydrocortisone up to 20 mg daily (QD) is
             allowed.

          8. Requirement for immunosuppressive therapy, such as those used to treat autoimmune
             disease.

          9. Concomitant malignancies or previous malignancies within the last 3 years, with the
             exception of adequately treated basal or squamous cell carcinoma of the skin or
             carcinoma in situ of the cervix.

         10. History of significant cardiac disease, cardiac risk factors or uncontrolled
             arrhythmias

         11. Ejection fraction <50% or below the lower limit of the institutional normal range,
             whichever is lower

         12. Known hypersensitivity to trastuzumab or pertuzumab

         13. Serious medical or psychiatric limitations likely to interfere with participation in
             this study.

         14. Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs,
             resulting in dyspnea at rest or requiring supplemental oxygen

         15. Patient is currently part of or has participated in any clinical trial of an
             investigational agent within 1 month prior to enrollment in this study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:2 years
Safety Issue:
Description:The primary objective of this study is to compare progression-free survival (PFS [also known as time to disease progression]) with the addition of pertuzumab to trastuzumab plus physician's choice of chemotherapy versus trastuzumab plus physician's choice of chemotherapy in patients who have previously received treatment with ado-trastuzumab emtansine (TDM1) for HER2+ metastatic breast cancer.

Secondary Outcome Measures

Measure:Progression-free survival (PFS) in patients (pts) with prior pertuzumab
Time Frame:2 years
Safety Issue:
Description:To assess PFS with the addition of pertuzumab to trastuzumab plus physician's choice of chemotherapy in patients who have received prior pertuzumab;
Measure:Progression-free survival (PFS) in pts with prior chemotherapy
Time Frame:2 years
Safety Issue:
Description:To compare median PFS with the addition of pertuzumab to trastuzumab plus physician's choice of chemotherapy in patients who have received 1 vs 2-3 prior chemotherapy regimens for metastatic disease;
Measure:Number of patients with complete and partial responses
Time Frame:2 years
Safety Issue:
Description:To compare the objective response rates (ORR; complete response [CR] plus partial response [PR]) between the two treatment arms;
Measure:Overall survival
Time Frame:2 years
Safety Issue:
Description:To assess overall survival (OS) in each of the treatment arms;
Measure:Number of adverse events and serious adverse events
Time Frame:2 years
Safety Issue:
Description:To assess the safety of pertuzumab in combination with trastuzumab and physician's choice of chemotherapy (vinorelbine, paclitaxel, nab-paclitaxel, docetaxel, or capecitabine).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:US Oncology Research

Trial Keywords

  • breast cancer
  • metastatic breast cancer
  • HER2+ breast cancer

Last Updated

May 18, 2017