Clinical Trials /

Paclitaxel + Trastuzumab + Pertuzumab as Pre-Op for Inflammatory BrCa

NCT01796197

Description:

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. In this study, paclitaxel and trastuzumab are being combined with pertuzumab which is "investigational" for the preoperative treatment of inflammatory breast cancer. Trastuzumab is given for a total of 12 months for the treatment of HER2 positive breast cancer. This study also adds pertuzumab to trastuzumab so that both drugs are given for a total of 12 months; this combination is also "investigational". "Investigational" means that pertuzumab is being studied. It also means that although the FDA has approved pertuzumab for preoperative use to treat breast cancer, it has not been thoroughly studied in combination with paclitaxel and trastuzumab for preoperative treatment of inflammatory breast cancer. It has been FDA approved for specific use in advanced breast cancer that is HER2 positive. Pertuzumab is an antibody, which is a protein that attacks a foreign substance is the body. Pertuzumab blocks the function of the HER2 protein like trastuzumab does. However, pertuzumab binds to a different part of the HER2 receptor and stops cancer cells from growing. This drug has been used in the treatment of advanced breast cancer that is HER2 positive, and has been combined with trastuzumab and chemotherapy in those studies. Information from those other research studies suggests that pertuzumab may help to kill the cancer cells in the breast and enable you to undergo a mastectomy. The addition of pertuzumab may also help reduce the chance of cancer recurrence. In this research study, we are combining pertuzumab with paclitaxel and trastuzumab as preoperative therapy and will determine the response of the cancer remaining in the breast at the time of mastectomy. In addition, we are combining trastuzumab with pertuzumab for a total of 12 months and we are looking to see whether the combination reduces the chance that the cancer will return. Another goal of this research study is to determine whether we can develop a way to identify tumors that will respond well to this study treatment. We will do research tests on your tumor tissue before, during and after study treatment. These tests may help doctors understand how the study treatment may work to treat your type of breast cancer. In the future, these tests may help us find ways to help match patients with the drugs most likely to work against their specific tumors before treatment begins.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Paclitaxel + Trastuzumab + Pertuzumab as Pre-Op for Inflammatory BrCa
  • Official Title: Phase II Trial of Paclitaxel Combined With Trastuzumab and Pertuzumab as Pre-Operative Therapy for Inflammatory Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 12-497
  • NCT ID: NCT01796197

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
TrastuzumabTreatment Arm
PertuzumabTreatment Arm
PaclitaxelTreatment Arm
DoxorubicinTreatment Arm
CyclophosphamideTreatment Arm

Purpose

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. In this study, paclitaxel and trastuzumab are being combined with pertuzumab which is "investigational" for the preoperative treatment of inflammatory breast cancer. Trastuzumab is given for a total of 12 months for the treatment of HER2 positive breast cancer. This study also adds pertuzumab to trastuzumab so that both drugs are given for a total of 12 months; this combination is also "investigational". "Investigational" means that pertuzumab is being studied. It also means that although the FDA has approved pertuzumab for preoperative use to treat breast cancer, it has not been thoroughly studied in combination with paclitaxel and trastuzumab for preoperative treatment of inflammatory breast cancer. It has been FDA approved for specific use in advanced breast cancer that is HER2 positive. Pertuzumab is an antibody, which is a protein that attacks a foreign substance is the body. Pertuzumab blocks the function of the HER2 protein like trastuzumab does. However, pertuzumab binds to a different part of the HER2 receptor and stops cancer cells from growing. This drug has been used in the treatment of advanced breast cancer that is HER2 positive, and has been combined with trastuzumab and chemotherapy in those studies. Information from those other research studies suggests that pertuzumab may help to kill the cancer cells in the breast and enable you to undergo a mastectomy. The addition of pertuzumab may also help reduce the chance of cancer recurrence. In this research study, we are combining pertuzumab with paclitaxel and trastuzumab as preoperative therapy and will determine the response of the cancer remaining in the breast at the time of mastectomy. In addition, we are combining trastuzumab with pertuzumab for a total of 12 months and we are looking to see whether the combination reduces the chance that the cancer will return. Another goal of this research study is to determine whether we can develop a way to identify tumors that will respond well to this study treatment. We will do research tests on your tumor tissue before, during and after study treatment. These tests may help doctors understand how the study treatment may work to treat your type of breast cancer. In the future, these tests may help us find ways to help match patients with the drugs most likely to work against their specific tumors before treatment begins.

Detailed Description

      If you agree to take part in this study we will ask you to undergo some screening tests and
      procedures to confirm that you are eligible. Many of these tests and procedures are likely to
      be part of regular cancer care and may be done even if it turns out that you do not take part
      in the research study. If you have had some of these tests or procedures recently, they may
      or may not have to be repeated. The screening process will include the following: a medical
      history, performance status, physical examination, scans and x-rays, blood samples, blood
      pregnancy test, electrocardiogram, echocardiogram. If these tests show that you are eligible
      to participate in the research study, you will begin the study treatment. If you do not meet
      the eligibility criteria you will not be able to participate in this research study.

      Before beginning study treatment you will undergo a tumor biopsy and have photographs of your
      tumor taken to assess the response of your tumor to the study treatment.

      On the first day of study treatment (Week 1, Day 1) with trastuzumab and pertuzumab, you will
      receive an intravenous infusion of trastuzumab over about 90 minutes, followed by a 60
      minutes observation period. If the trastuzumab infusion is tolerated, you will receive the
      rest of your study treatment, the pertuzumab. This will also be given as an intravenous
      infusion over about 60 minutes with you being observed for a further 60 minutes. Thus, the
      total duration of infusion and observation periods for the first dose of study treatment
      (Week 1, Day 1) is about 5 hours. If the drugs are well tolerated at Week 1, the duration of
      the infusion with trastuzumab and pertuzumab may be shortened for subsequent doses.

      Prior to starting Week 2, you will undergo a second research biopsy of your breast. The
      biopsy will be performed either prior to Week 2, Day 8 or on the same day. You will then
      receive an infusion of trastuzumab and begin chemotherapy. If the infusion of trastuzumab was
      tolerated on Week 1, Day 1, then the infusion time is reduced to about 30 minutes. You will
      then be pre-medicated with drugs to reduce the chance of having a sensitivity reaction to
      paclitaxel. This takes approximately 30 minutes. The paclitaxel is give by intravenous
      infusion over about 60 minutes. If you tolerate the paclitaxel infusions, then the
      pre-medication can be changed by your doctor.

      The pertuzumab is given every 3 weeks beginning on Week 1 and continues until paclitaxel
      administration is complete. Trastuzumab is given weekly beginning on Week 1 and continues
      until paclitaxel administration is complete. Paclitaxel is given weekly for a total of 16
      doses beginning on Week 2. After completing 16 doses of paclitaxel, trastuzumab and
      pertuzumab may be continued every 3 weeks until surgery.

      Study treatment visits will occur at regular intervals during the period of study treatment,
      beginning on Week 1. During these study treatment visits the following will be done: physical
      exam, performance status, blood samples, heart function tests.

      After completing 16 doses of paclitaxel in combination with pertuzumab and trastuzumab, you
      will undergo surgery for removal of your breast cancer. This will occur approximately 4-5
      weeks after your last paclitaxel infusion. Prior to surgery, you will have the following
      assessments: a repeat breast MRI, PET scan (if necessary), physical exam, vital signs,
      performance status, blood tests, tumor tissue tests.

      Approximately 4-5 weeks after surgery, when you are well-healed, you will have two options
      for treatment (at your physician's discretion):

      Option 1: Doxorubicin and cyclophosphamide (AC), every 2-3 weeks x 4 cycles. This is standard
      chemotherapy for IBC. Followed by trastuzumab and pertuzumab every 3 weeks to complete 12
      months of HER2-directed therapy.

      Option 2: Continue trastuzumab and pertuzumab every 3 weeks to complete 12 months of
      HER2-directed therapy.

      Doxorubicin is given by vein over about 5-10 minutes. This is followed by cyclophosphamide by
      vein given about 30 minutes. Anti-nausea medicine is given first under the direction of your
      doctor.

      Approximately 4-5 weeks after finishing the AC treatment if you pursue Option 1 (or 4-5 weeks
      after surgery if you pursue Option 2), you will receive radiation therapy to the mastectomy
      site and the surrounding lymph nodes. This will be given daily, Monday through Friday for
      approximately 6-7 weeks. This will be administered as standard of care for IBC.

      Approximately 3-4 weeks following the completion of AC if you pursue Option 1 (or 3-4 weeks
      after surgery if you pursue Option 2), you will begin maintenance therapy with trastuzumab
      and pertuzumab. As with Week 1, Day 1, you will receive an intravenous infusion of
      trastuzumab over about 90 minutes followed by a 60 minute observation period. If the
      trastuzumab infusion is tolerated, you will receive the rest of your study treatment, the
      pertuzumab. This will also be given as an intravenous infusion over about 60 minutes with
      your being observed for a further 60 minutes. Thus, the total duration of infusion and
      observation periods for the first day of maintenance study treatment is about 5 hours. If the
      study drugs are well tolerated, the duration of the infusion with trastuzumab and pertuzumab
      may be shortened for subsequent doses. Both trastuzumab and pertuzumab will be given every 3
      weeks to complete a 12 month duration of HER2-directed therapy. Every 9 weeks (every third
      dose of trastuzumab and pertuzumab) you will undergo the same procedure as taht described
      above in Study Treatment visits.

      About one month after your last dose of study treatment, you will be asked to return to the
      clinic. At this visit tests will be done to check your physical condition and to check that
      you have recovered from any side effects of study treatment. During this visit the following
      will be done: physical exam, vital signs, performance status and blood tests.

      You will be asked to attend regular follow up visits to check if you are experiencing any
      long term side effects and to check taht the cancer has not come back. We plan to follow
      participants for up to 13 years after the start of teh study. During these visits the
      following will be done: physical exam and questions about your health/medications you have
      taken (every 3 months for the first year, every 6 months for the next 4 years, yearly until
      the end of study follow up); blood draws (every 6 months for the first 4 years, yearly after
      that); mammograms will be performed annually, other scans may be performed as needed.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment ArmExperimentalRun in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment: Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Radiation Therapy
  • Trastuzumab
  • Pertuzumab
  • Paclitaxel
  • Doxorubicin
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed invasive breast cancer

          -  HER2 positive breast cancer

          -  Clinical diagnosis of inflammatory breast cancer

          -  Without evidence of visceral or bone involvement with metastatic cancer on physical
             exam or any diagnostic study. Extensive nodal involvement is allowed

          -  Willingness to undergo a research biopsy of the affected breast

        Exclusion Criteria:

          -  Prior therapy for the treatment of breast cancer

          -  Receiving any other investigational or commercial agents or therapies

          -  Known brain metastases

          -  Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs
             resulting in dyspnea at rest

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to paclitaxel, trastuzumab, pertuzumab

          -  Uncontrolled intercurrent illness

          -  Pregnant or breastfeeding

          -  History of a different malignancy except for the following circumstances: disease-free
             for at least 5 years and at low risk of recurrence, or cervical cancer in situ or
             basal or squamous cell carcinoma of the skin

          -  HIV positive on combination anti-retroviral therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic complete response rate
Time Frame:2 years
Safety Issue:
Description:To determine pathologic complete response (pCR) rate after preoperative therapy with combination paclitaxel (T), trastuzumab (H) and pertuzumab (P) in HER2+ inflammatory breast cancer

Secondary Outcome Measures

Measure:Assess toxicity of protocol therapy
Time Frame:2 years
Safety Issue:
Description:To assess the toxicity of protocol therapy, including clinically-significant CHF
Measure:Determine efficacy of therapy
Time Frame:2 years
Safety Issue:
Description:To determine the efficacy of therapy defined as disease-free survival (DFS), time to treatment failure (TTF), and overall survival (OS)
Measure:Assess microarray analysis on pre-treatment biopsy specimens
Time Frame:2 years
Safety Issue:
Description:To assess microarray analysis on pre-treatment breast cancer biopsy specimens using PAM50 to correlate the intrinsic subtype with pCR
Measure:Assess microarray analysis on residual disease
Time Frame:2 years
Safety Issue:
Description:To assess microarray analysis on residual disease within the breast accessed at the time of mastectomy and by using PAM50 to correlate the intrinsic subtype of the resistance clone with residual disease
Measure:Identify early adaptive responses
Time Frame:2 years
Safety Issue:
Description:To identify early adaptive responses that are associated with resistance to HER2 directed therapies, i.e., trastuzumab and pertuzumab, but analyzing breast tissue specimens obtained 8 days after exposure to only HER2 directed treatment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Last Updated

June 30, 2017