Chemotherapy and Peripheral Stem Cell Transplantation Followed by Trastuzumab in Treating Women With Metastatic Breast Cancer

May 10, 2018 updated by: David Avigan, MD, Beth Israel Deaconess Medical Center

Autotransplantation and Her 2 Neu Antibody Immunotherapy in Advanced Breast Cancer

RATIONALE: Chemotherapy uses different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I/II trial to study the effectiveness of chemotherapy and peripheral stem cell transplantation followed by trastuzumab in treating women who have metastatic breast cancer.

Study Overview

Detailed Description

OBJECTIVES: I. Determine the safety and toxicity profile, specifically cardiac toxicity, of trastuzumab (Herceptin) following high dose chemotherapy and autologous peripheral blood stem cell transplantation in women with metastatic breast cancer. II. Determine the time to disease progression and disease free survival in these patients when treated with this regimen. III. Determine the impact of trastuzumab (Herceptin) on minimal residual disease after autologous peripheral blood stem cell transplantation as evidenced by serial immunocytochemical analysis of bone marrow. IV. Determine the relationship between posttransplant reconstitution of antibody dependent cellular toxicity and the efficacy of trastuzumab (Herceptin) in these patients.

OUTLINE: This is a multicenter study. Patients undergo stem cell mobilization with growth factors alone (filgrastim (G-CSF) and/or sargramostim (GM-CSF)) or chemotherapy followed by growth factors (depending on center). Peripheral blood stem cells (PBSC) are then collected by leukapheresis. Patients then receive high dose chemotherapy consisting of cyclophosphamide IV over 1 hour and cisplatin IV over 72 hours on days -6 to -4 and carmustine IV on day -3 or cyclophosphamide IV, thiotepa IV, and carboplatin IV over 96 hours on days -7 to -4 (depending on center). PBSC are reinfused on day 0. Patients then receive trastuzumab IV over 30-90 minutes weekly for 1 year or until disease progression beginning 5-8 weeks after PBSC reinfusion.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS: Histologically confirmed stage IV breast cancer that overexpresses HER2/neu Evidence of at least a partial response (at least 50% reduction) to salvage chemotherapy as initial chemotherapy for metastatic disease Measurable disease not required if there is no disease progression at induction chemotherapy Bone lesions as only site of metastatic disease allowed if evidence of clinical improvement and no new lesions on x-ray No CNS metastases Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: 18 to physiologic 65 Sex: Female Menopausal status: Pre or postmenopausal Performance status: Karnofsky 80-100% Life expectancy: At least 6 months Hematopoietic: WBC at least 2,500/mm3 Absolute neutrophil count at least 1,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT no greater than 2.5 times ULN Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: LVEF at least 45% by radionucleotide ventriculogram No uncontrolled hypertension No unstable angina No New York Heart Association class IV heart disease or congestive heart failure No coronary angioplasty or myocardial infarction within past 6 months No uncontrolled atrial or ventricular cardiac arrhythmias Pulmonary: FEV1 and DLCO at least 50% Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No insulin dependent diabetes mellitus No uncontrolled active systemic infection No other significant nonmalignant disease No other malignancy in past 5 years except surgically cured nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior trastuzumab allowed No prior bone marrow or peripheral blood stem cell transplantation Chemotherapy: See Disease Characteristics Prior doxorubicin not to exceed total cumulative dose of 360 mg/m2 No more than 6 standard courses of pretransplant salvage chemotherapy No more than 3 months of prior weekly taxane therapy More than 1 chemotherapy regimen allowed with no progression during chemotherapy Endocrine therapy: Concurrent tamoxifen therapy allowed for estrogen receptor positive patients who have not received prior hormonal therapy No other concurrent hormonal therapy Radiotherapy: No concurrent radiotherapy Surgery: Not specified Other: Concurrent pamidronate allowed for bone lesions

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: David Avigan, MD, Beth Israel Deaconess Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2000

Primary Completion (Actual)

July 1, 2000

Study Completion (Actual)

July 1, 2000

Study Registration Dates

First Submitted

August 3, 2000

First Submitted That Met QC Criteria

February 11, 2004

First Posted (Estimate)

February 12, 2004

Study Record Updates

Last Update Posted (Actual)

May 16, 2018

Last Update Submitted That Met QC Criteria

May 10, 2018

Last Verified

May 1, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on carboplatin

3
Subscribe