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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01779050
First Posted: January 29, 2013
Last Update Posted: January 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Washington University School of Medicine
  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
Intervention Model: Parallel Assignment
Masking: None (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 ]
    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 ]

    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: 6-18 months ]
    Bone marrow samples collected at baseline and 6-18 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.


Enrollment: 7
Study Start Date: December 19, 2013
Estimated Study Completion Date: October 31, 2019
Estimated Primary Completion Date: October 31, 2019 (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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes 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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01779050


Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
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
First Submitted: January 25, 2013
First Posted: January 29, 2013
Last Update Posted: January 27, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Docetaxel
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Cyclophosphamide
Carboplatin
Doxorubicin
Trastuzumab
Fluorouracil
Epirubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors