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

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

Overview[ - collapse ][ - ]

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	Breast Neoplasms
Intervention	Drug: Doxorubicin Biological: Trastuzumab Drug: Cyclophosphamide Drug: Paclitaxel
Phase	Phase 2
Sponsor	Washington University School of Medicine
Responsible Party	Washington University School of Medicine
ClinicalTrials.gov Identifier	NCT01779050
First Received	January 25, 2013
Last Updated	January 27, 2014
Last verified	January 2014

Tracking Information[ + expand ][ + ]

First Received Date	January 25, 2013
Last Updated Date	January 27, 2014
Start Date	December 2013
Estimated Primary Completion Date	September 2022
Current 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
Current 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.

Descriptive Information[ + expand ][ + ]

Brief Title	Effect of Trastuzumab on Disease Free Survival in Early Stage HER2-Negative Breast Cancer Patients With ERBB2 Expressing Disseminated Tumor Cells
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
Brief Summary	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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 2
Study Design	Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Breast Neoplasms
Intervention	Drug: Doxorubicin Other Names: Adriamycin®, Rubex®, Hydroxydaunomycin Hydrochloride, Hydroxydoxorubicin HydrochlorideBiological: Trastuzumab Other Names: •Herceptin®Drug: Cyclophosphamide Other Names: Cytoxan®, CPM, CTX, CYTDrug: Paclitaxel Other Names: Abraxane®, Onxol®
Study Arm (s)	Active Comparator: Arm I (definitive therapy) Patients receive definitive surgery and standard chemotherapy comprising doxorubicin hydrochloride IV and cyclophosphamide IV every 2 weeks for 4 courses followed by high-dose paclitaxel IV every 2 weeks for 4 courses or low-dose paclitaxel weekly for 12 weeks in the absence of disease progression or unacceptable toxicity. Experimental: Arm II (definitive therapy, trastuzumab) Patients receive definitive surgery and standard chemotherapy comprising doxorubicin hydrochloride, cyclophosphamide, and higher or lower dose paclitaxel as in Arm I. Patients will also receive trastuzumab IV over 30-90 minutes for 52 weeks starting at initiation of paclitaxel. While trastuzumab and paclitaxel are being coadministered, both agents will be dosed on the same days. Trastuzumab will be given every 3 weeks following completion of paclitaxel treatment. Treatment continues in the absence of disease progression or unacceptable toxicity.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	50
Estimated Completion Date	September 2022
Estimated Primary Completion Date	September 2017
Eligibility Criteria	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. - Presence of bone marrow ERBB2 over-expressing DTCs at the time of diagnosis; bone marrow aspiration will be performed in consented patients to evaluate DTCs following preregistration provided patients meet all eligibility criteria as described in this section. - A candidate for adjuvant or neoadjuvant chemotherapy. 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. - Adequate cardiac function as demonstrated by LVEF of >55% performed no more than 2 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 - Patient (or legally authorized representative) must be able to understand and willing to sign a written informed consent document. - 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. Exclusion Criteria: - Evidence of distant metastasis present by CT scan, bone scan, or physical exam. - Undergoing treatment with other standard or investigational anti-cancer agents at the time of enrollment. - Prior chemotherapy for this cancer (excluding doxorubicin and cyclophosphamide as described in the treatment section of the protocol). - Prior radiation therapy for this cancer. - Previous treatment with trastuzumab or any other Her2 targeted therapy. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to trastuzumab. - 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. - 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.
Gender	Female
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Rebecca Aft, M.D., Ph.D. 314-747-0063 aftr@wudosis.wustl.edu
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01779050
Other Study ID Numbers	201309084
Has Data Monitoring Committee	No
Information Provided By	Washington University School of Medicine
Study Sponsor	Washington University School of Medicine
Collaborators	Not Provided
Investigators	Principal Investigator: Rebecca Aft, M.D., Ph.D. Washington University School of Medicine
Verification Date	January 2014

Locations[ + expand ][ + ]

Washington University School of Medicine	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. Recruiting