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

Primary Purpose

Breast Cancer

Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
trastuzumab
carboplatin
carmustine
cisplatin
cyclophosphamide
thiotepa
peripheral blood stem cell transplantation
Sponsored by
Beth Israel Deaconess Medical Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring stage IV breast cancer

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Beth Israel Deaconess Medical Center
  • Hackensack University Medical Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
August 3, 2000
Last Updated
May 10, 2018
Sponsor
Beth Israel Deaconess Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT00006123
Brief Title
Chemotherapy and Peripheral Stem Cell Transplantation Followed by Trastuzumab in Treating Women With Metastatic Breast Cancer
Official Title
Autotransplantation and Her 2 Neu Antibody Immunotherapy in Advanced Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Withdrawn
Why Stopped
Never started
Study Start Date
July 2000 (undefined)
Primary Completion Date
July 2000 (Actual)
Study Completion Date
July 2000 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beth Israel Deaconess Medical Center

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
stage IV breast cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
trastuzumab
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Type
Drug
Intervention Name(s)
carmustine
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
thiotepa
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Avigan, MD
Organizational Affiliation
Beth Israel Deaconess Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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