Effect of Trastuzumab on Disease Free Survival in Early Stage HER2-Negative Breast Cancer Patients With ERBB2 Expressing Disseminated Tumor Cells

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01779050
First received: January 25, 2013
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

This phase II trial studies the efficacy of trastuzumab treatment in breast cancer patients with stage II-III human epidermal growth factor receptor 2 (HER2)-negative tumors and HER2-expressing bone marrow disseminated tumor cells. Administering targeted trastuzumab therapy to these patients may result in the elimination of HER2 expressing disseminated tumor cells and improved disease free survival.


Condition Intervention Phase
Breast Neoplasms
Drug: Doxorubicin
Biological: Trastuzumab
Drug: Cyclophosphamide
Drug: Paclitaxel
Drug: Epirubicin
Drug: Docetaxel
Drug: Carboplatin
Drug: Fluorouracil
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Randomized Trial Evaluating the Effect of Trastuzumab on Disease Free Survival in Early Stage HER2-Negative Breast Cancer Patients With ERBB2 Expressing Bone Marrow Disseminated Tumor Cells

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Recurrence Rate at 3 years [ Time Frame: 3 years after completion of standard chemotherapy and surgery ] [ Designated as safety issue: No ]
    Rate for patients receiving trastuzumab in addition to standard chemotherapy and for patients receiving standard chemotherapy alone; calculated using Cox proportional hazards models

  • Death rate at 3 years [ Time Frame: 3 years after completion of definitive therapy ] [ Designated as safety issue: No ]

    Death rate at 3 years Rate for patients receiving trastuzumab in addition to standard chemotherapy and for patients receiving standard chemotherapy alone; calculated using Cox proportional hazards models 3 years after completion of definitive therapy (3.5 years) No

    Secondary Outcome Measures Title Description Time Frame Safety Issue? Elimination of ERBB2 expressing bone marrow DTCs Bone marrow samples collected at baseline and 14 months later; Fisher's exact test will be used to compare the proportion of patients who eliminate ERBB2-positive DTCs from BM in the two study arms. 14 months No



Secondary Outcome Measures:
  • Elimination of ERBB2 overexpressing bone marrow DTCs [ Time Frame: 14 months ] [ Designated as safety issue: No ]
    Bone marrow samples collected at baseline and 14 months later; Fisher's exact test will be used to compare the proportion of patients who eliminate ERBB2-positive DTCs from BM in the two study arms.


Estimated Enrollment: 50
Study Start Date: December 2013
Estimated Study Completion Date: September 2022
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (definitive therapy)

Patients receive definitive surgery and best practice standard chemotherapy according to NCCN guidelines. The 5 chemo backbone options are:

  • doxorubicin or epirubicin plus cyclophosphamide followed by paclitaxel or docetaxel
  • docetaxel plus cyclophosphamide
  • single-agent paclitaxel
  • docetaxel plus carboplatin
  • fluorouracil plus epirubicin plus cyclophosphamide followed by paclitaxel or docetaxel
Drug: Doxorubicin
Other Name: Adriamycin®, Rubex®, Hydroxydaunomycin Hydrochloride, Hydroxydoxorubicin Hydrochloride
Drug: Cyclophosphamide
Other Name: Cytoxan®, CPM, CTX, CYT
Drug: Paclitaxel
Other Name: Abraxane®, Onxol®
Drug: Epirubicin
Other Name: Ellence, Pharmorubicin, Epirubicin ebewe
Drug: Docetaxel
Other Name: Taxotere, Docefrez
Drug: Fluorouracil
Other Name: 5-FU, Adrucil
Experimental: Arm II (definitive therapy, trastuzumab)

Patients receive definitive surgery and best practice standard chemotherapy according to NCCN guidelines. The 5 chemo backbone options are:

  • doxorubicin or epirubicin plus cyclophosphamide followed by paclitaxel or docetaxel
  • docetaxel plus cyclophosphamide
  • single-agent paclitaxel
  • docetaxel plus carboplatin
  • fluorouracil plus epirubicin plus cyclophosphamide followed by paclitaxel or docetaxel

Patients will also receive trastuzumab IV over 30-90 minutes for 52 weeks starting such that there is a minimum of 8 weeks of overlap with the standard of care chemotherapy. Trastuzumab may be given weekly, every 2 weeks, or every 3 weeks while overlapping with standard of care chemotherapy. Trastuzumab will be given every 3 weeks after all standard of care chemotherapy has concluded. Treatment continues in the absence of disease progression or unacceptable toxicity.

Drug: Doxorubicin
Other Name: Adriamycin®, Rubex®, Hydroxydaunomycin Hydrochloride, Hydroxydoxorubicin Hydrochloride
Biological: Trastuzumab
Other Name: •Herceptin®
Drug: Cyclophosphamide
Other Name: Cytoxan®, CPM, CTX, CYT
Drug: Paclitaxel
Other Name: Abraxane®, Onxol®
Drug: Epirubicin
Other Name: Ellence, Pharmorubicin, Epirubicin ebewe
Drug: Docetaxel
Other Name: Taxotere, Docefrez
Drug: Carboplatin
Other Name: cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II), Paraplatin, Paraplatin-AQ
Drug: Fluorouracil
Other Name: 5-FU, Adrucil

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Pre-Registration Inclusion Criteria:

  • Histologically confirmed HER2-negative primary invasive ductal or invasive lobular breast carcinoma. For patients enrolling for neoadjuvant treatment, diagnosis must be clinical stage II or III; for patients enrolling for adjuvant treatment, diagnosis must be pathologic stage IIA to IIIC. Standard HER2 testing will be performed in the surgical specimen at Washington University according to the standard of care in the Department of Pathology. A HER2-negative primary breast cancer sample from a patient eligible for randomization should have a HER2 IHC score of 0 or 1+ Those patients with IHC score of 2+ should be HER2 FISH-negative in standard testing. Patient will have undergone staging studies including a CT of the chest/abdomen/pelvis and bone scan and/or PET scan either prior to the initiation of treatment or prior to entry into the trial. In addition, patients with non-metastatic, HER2-negative, recurrent tumors who need chemotherapy are eligible.
  • Planning to receive best practice adjuvant or neoadjuvant chemotherapy according to institutional guidelines. Adjuvant tamoxifen or aromatase inhibitors treatment will be allowed for hormone receptor-positive patients. Patients who have failed neoadjuvant endocrine therapy will also be eligible.
  • At least 18 years old.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  • Patient (or legally authorized representative) must be able to understand and willing to sign a written informed consent document.

Pre-Registration Exclusion Criteria:

  • Prior chemotherapy for this cancer (excluding initiation of best practice chemotherapy to be given as standard of care as described in this protocol, which may be initiated after the pre-registration bone marrow collection but before final confirmation of eligibility and randomization).
  • Previous treatment with trastuzumab or any other Her2 targeted therapy.
  • Presence of an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Registration Inclusion Criteria

  • Presence of bone marrow ERBB2 overexpressing DTCs at the time of diagnosis; bone marrow aspiration will be performed in consented patients to evaluate DTCs following pre-registration provided patients meet all eligibility criteria as described in this section.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  • Adequate cardiac function as demonstrated by LVEF of >55% performed no more than 4 weeks prior to randomization.
  • Normal organ and marrow function as defined below:

    • leukocytes ≥3,000/mcL
    • absolute neutrophil count ≥1,500/mcL
    • platelets ≥100,000/mcL
    • hemoglobin ≥ 10 g/dL
    • total bilirubin within institutional upper limits of normal unless related to primary disease
    • AST(SGOT)/ALT(SGPT) ≤2.0 X institutional upper limit of normal
    • Creatinine ≤ 1.5 institutional upper limits of normal OR creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • If a woman of childbearing potential, patient must use two forms of effective contraception for a minimum of 6 months following trastuzumab. Effective methods of birth control include use of established oral, injected, or implanted hormonal methods of birth control, IUD, IUS, and condoms.

Registration Exclusion Criteria

  • Evidence of distant metastasis present by CT scan, bone scan, or physical exam.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to trastuzumab.
  • Prior chemotherapy for this cancer (excluding initiation of best practice chemotherapy to be given as standard of care described in this protocol, which may be initiated after the pre-registration bone marrow collection but before final confirmation of eligibility and randomization).
  • History of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
  • Pregnant or breastfeeding. Patient must have a negative serum pregnancy test ≤ 7 days from date of registration (if a woman of childbearing potential).
  • Clinically important history of active liver disease, including viral or other hepatitis or cirrhosis.
  • Uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia defined as less than the lower limit of normal for the institution despite adequate electrolyte supplementation.
  • Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest.
  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: NCT01779050

Contacts
Contact: Rebecca Aft, M.D., Ph.D. 314-747-0063 aftr@wudosis.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Rebecca Aft, M.D., Ph.D.    314-747-0063    aftr@wudosis.wustl.edu   
Sub-Investigator: Foluso Ademuyiwa, M.D.         
Sub-Investigator: Mark Watson, M.D., Ph.D.         
Sub-Investigator: Ron Bose, M.D., Ph.D.         
Sub-Investigator: Matthew Ellis, M.B., Ph.D.         
Sub-Investigator: Michael Naughton, M.D.         
Sub-Investigator: Steven Sorscher, M.D.         
Sub-Investigator: Rama Suresh, M.D.         
Sub-Investigator: Timothy Eberlein, M.D.         
Sub-Investigator: William Gillanders, M.D.         
Sub-Investigator: Julie Margenthaler, M.D.         
Sub-Investigator: Amy Cyr, M.D.         
Sub-Investigator: Deb Novack, M.D., Ph.D.         
Sub-Investigator: Cynthia Ma, M.D., Ph.D.         
Sub-Investigator: Adel Tabchy, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Rebecca Aft, M.D., Ph.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01779050     History of Changes
Other Study ID Numbers: 201309084
Study First Received: January 25, 2013
Last Updated: May 15, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 28, 2014