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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Dana-Farber Cancer Institute
Sponsor:
Information provided by (Responsible Party):
Beth Overmoyer, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01796197
First received: February 20, 2013
Last updated: February 10, 2014
Last verified: February 2014
  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. Preoperative paclitaxel and trastuzumab are used as standard preoperative treatment for HER2 positive inflammatory breast cancer. In this study, paclitaxel and trastuzumab are being combined with pertuzumab which is "investigational". 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 the FDA has not yet approved pertuzumab for preoperative use to treat your type of 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.


Condition Intervention Phase
Breast Cancer
Drug: Trastuzumab
Drug: Pertuzumab
Drug: Paclitaxel
Drug: Doxorubicin
Drug: Cyclophosphamide
Procedure: Mastectomy
Radiation: Radiation Therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Paclitaxel Combined With Trastuzumab and Pertuzumab as Pre-Operative Therapy for Inflammatory Breast Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Pathologic complete response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine pathologic complete response (pCR) rate after preoperative therapy with combination paclitaxel (T), trastuzumab (H) and pertuzumab (P) in HER2+ inflammatory breast cancer

  • Assess residual cancer burden [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess the residual cancer burden (RCB) after preoperative therapy with combination paclitaxel (T), trastuzumab (H) and pertuzumab (P) in HER2+ inflammatory breast cancer.


Secondary Outcome Measures:
  • Assess toxicity of protocol therapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To assess the toxicity of protocol therapy, including clinically-significant CHF

  • Determine efficacy of therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the efficacy of therapy defined as disease-free survival (DFS), time to treatment failure (TTF), and overall survival (OS)

  • Assess microarray analysis on pre-treatment biopsy specimens [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess microarray analysis on pre-treatment breast cancer biopsy specimens using PAM50 to correlate the intrinsic subtype with pCR

  • Assess microarray analysis on residual disease [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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

  • Identify early adaptive responses [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 30
Study Start Date: March 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
Run 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 weeks, starting Day 22 (week 3) Pertuzumab 420 mg IV every 21 days x 5 doses Modified Radical Mastectomy Post-surgical: Doxorubicin 60 mg/m2 IV, Cyclophosphamide 600 mg/m2 IV every 3 weeks x 4 cycles; followed by Trastuzumab IV 8 mg/kg and Pertuzumab IV 840 mg; followed by Trastuzumab 6 mg/kg every 21 days and Pertuzumab 420 mg IV every 21 days x 12 doses Radiation Therapy
Drug: Trastuzumab Drug: Pertuzumab Drug: Paclitaxel Drug: Doxorubicin Drug: Cyclophosphamide Procedure: Mastectomy Radiation: Radiation Therapy

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01796197

Contacts
Contact: Beth Overmoyer, MD 6176324056 bovermoyer@partners.org

Locations
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Beth Overmoyer, MD    617-632-4056    bovermoyer@partners.org   
Principal Investigator: Beth Overmoyer, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Beth Overmoyer, MD    617-632-4056    bovermoyer@partners.org   
Principal Investigator: Beth Overmoyer, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Beth Overmoyer, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Beth Overmoyer, MD, Prinicipal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01796197     History of Changes
Other Study ID Numbers: 12-497
Study First Received: February 20, 2013
Last Updated: February 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Paclitaxel
Pertuzumab
Trastuzumab
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on November 24, 2014