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

NCT01796197 | Completed Phase 2 Results DMC

• 1 other identifier: 12-497
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Percentages of Participants With Pathologic Complete Response

  Pathologic complete response (pCR) is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Participants whose disease is not surgically resectable following preoperative treatment are considered as not having pCR.

  18 weeks

• Residual Cancer Burden Rate

  Residual cancer burden is calculated an then categorized based on the methods described in the following: Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 2007;25(28): 4414-22. This method uses tumor size, the proportion of that tumor that is invasive carcinoma, the number of axillary lymph nodes containing metastatic carcinoma and the diameter of the largest metastasis in an axillary lymph node. These parameters are combined in a formula that outputs a RCB index. This index is divided into 4 categories: RCB-0, RCB-I, RCB-II, and RCB-III. The previous categories are in order of increasing severity of RCB.

  18 Weeks

Secondary Outcomes (8)

• Number of Participants With Congestive Heart Failure

  1 year and 8 months

• Median Disease Free Survival

  63 months

• Median Time to Treatment Failure

  63 months

• Median Overall Survival

  63 months

• Pathological Complete Response Rate by Intrinsic Subtype

  18 Weeks

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Run in: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1 Week 1) Pre-Op: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8 Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above, add Pertuzumab 420 mg IV x 3 weeks. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued x 3 weeks until surgery Modified Radical Mastectomy Post-Op: Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV x 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 x 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation to the chest wall / regional lymph nodes and endocrine therapy by standard of care.

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Paclitaxel; Drug: Doxorubicin; Drug: Cyclophosphamide; Procedure: Mastectomy; Radiation: Radiation Therapy

Interventions

Trastuzumab DRUG

Treatment Arm

Pertuzumab DRUG

Treatment Arm

Paclitaxel DRUG

Treatment Arm

Doxorubicin DRUG

Treatment Arm

Cyclophosphamide DRUG

Treatment Arm

Mastectomy PROCEDURE

Treatment Arm

Radiation Therapy RADIATION

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (3)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Pernas S, Guerriero JL, Naumenko S, Goel S, Regan MM, Hu J, Harrison BT, Lynce F, Lin NU, Partridge A, Morikawa A, Hutchinson J, Mittendorf EA, Sokolov A, Overmoyer B. Early on-treatment transcriptional profiling as a tool for improving pathological response prediction in HER2-positive inflammatory breast cancer. Ther Adv Med Oncol. 2022 Jul 30;14:17588359221113269. doi: 10.1177/17588359221113269. eCollection 2022.

  PMID: 35923923 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; pertuzumab; Paclitaxel; Doxorubicin; Cyclophosphamide; Mastectomy; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Surgical Procedures, Operative; Therapeutics

Results Point of Contact

• Title: Beth Overmoyer, MD, FACP
• Organization: Dana-Farber Cancer Institute

beth_overmoyer@dfci.harvard.edu

617.632.3800

Study Officials

• Filipa Lynce, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: February 20, 2013
• First Posted: February 21, 2013
• Study Start: August 1, 2013
• Primary Completion: June 1, 2018
• Study Completion: January 1, 2026
• Last Updated: February 5, 2026
• Results First Posted: September 5, 2021

Record last verified: 2026-01

Locations

US (3)