Radioimmunotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Stage IV Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
ClinicalTrials.gov Identifier:
NCT00004085
First received: December 10, 1999
Last updated: June 21, 2011
Last verified: June 2011
  Purpose

RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and deliver tumor-killing substances to them. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by radioimmunotherapy used to kill tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of radiolabeled monoclonal antibody therapy plus peripheral stem cell transplantation in treating patients who have stage IV breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: filgrastim
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: yttrium Y 90 monoclonal antibody MN-14
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of High-Dose Radioimmunotherapy With a 90Y-Humanized MN-14 Anti-Carcinoembryonic Antigen (CEA) Antibody for the Treatment of Stage IV Breast Cancer

Resource links provided by NLM:


Further study details as provided by Garden State Cancer Center at the Center for Molecular Medicine and Immunology:

Primary Outcome Measures:
  • Safety [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    maximum tolerated dose


Estimated Enrollment: 15
Study Start Date: May 1998
Primary Completion Date: May 2002 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: filgrastim
    as prescribed by physician
    Procedure: autologous bone marrow transplantation
    1-2 weeks prior to treatment
    Procedure: peripheral blood stem cell transplantation
    1-2 weeks prior to treatment
    Radiation: yttrium Y 90 monoclonal antibody MN-14
    intravenous infusion over 30 min, single dose
Detailed Description:

OBJECTIVES: I. Determine the maximum tolerated dose and dose-limiting toxicity of yttrium Y 90 monoclonal antibody MN-14 (Y90 MOAB MN-14) plus peripheral blood stem cell rescue in patients with stage IV breast cancer. II. Determine the pharmacokinetic profile of Y90 MOAB MN-14 in the blood, normal organs, and tumors of this patient population. III. Determine the antibody response to Y90 MOAB MN-14 in these patients. IV. Determine the antitumor effect of this regimen in these patients. V. Determine the radiation absorbed dose to normal organs and tumors.

OUTLINE: This is a dose-escalation, multicenter study. Patients receive filgrastim (G-CSF) subcutaneously (SC) with or without chemotherapy on days -28 to -14 and peripheral blood stem cell (PBSC) collection on days -14 to -11. If an adequate number of CD34+ cells are not harvested, bone marrow may be collected. Patients receive pretherapy imaging with indium In 111 monoclonal antibody MN-14 IV for up to 40 minutes on day -7 followed by whole body imaging on days -7 to 0. Patients receive yttrium Y 90 monoclonal antibody MN-14 (Y90 MOAB MN-14) IV for up to 40 minutes on day 0. PBSC or bone marrow is reinfused on days 6 to 14, depending on antibody clearance. Patients receive G-CSF SC or IV until blood counts recover. Cohorts of 3-6 patients receive escalating doses of Y90 MOAB MN-14 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients are followed weekly for 2 months, monthly for 6 months, and then every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 24-30 patients will be accrued for this study within 2.5 years.

  Eligibility

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

DISEASE CHARACTERISTICS: Histologically or cytologically proven stage IV breast cancer Measurable disease after firstline or greater chemotherapy Evidence of CEA expression by: Serum CEA at least 10 ng/mL OR Positive immunostaining of primary or metastatic tumors with a CEA-specific antibody Positive imaging of at least 1 confirmed tumor by pre-therapy indium In 111 monoclonal antibody MN-14 No brain metastases Bone marrow biopsy prior to stem cell mobilization required to assess cellularity and tumor involvement Cellularity greater than 60% of normal Tumor involvement less than 25% Chromosome analysis of bone marrow aspirate (optional) No brain metastases Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: 18 and over Sex: Not specified Menopausal status: Not specified Performance status: Karnofsky 70-100% OR ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: WBC at least 3,000/mm3 Granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin less than 2 mg/dL AST less than 2 times upper limit of normal (ULN) Renal: Creatinine less than 1.5 times ULN Cardiovascular: Cardiac ejection fraction greater than 50% by MUGA Pulmonary: DLCO greater than 70% of predicted FVC and FEV1 greater than 70% of predicted Other: Not pregnant Negative pregnancy test Fertile patients must use effective contraception No severe anorexia, nausea or vomiting, or urinary incontinence No other significant concurrent medical problem including severe psychiatric, epileptic, or diabetic disease No prisoners If received prior chimeric or humanized antibody (e.g., trastuzumab (Herceptin)), must not have allergy to yttrium Y 90 monoclonal antibody MN-14

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior peripheral blood stem cell rescue Chemotherapy: See Disease Characteristics At least 1 course of prior chemotherapy At least 4 weeks since prior chemotherapy No prior high-dose chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy No prior radiotherapy to more than 30% of red bone marrow Surgery: At least 4 weeks since prior major surgery

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004085

Locations
United States, New Jersey
Garden State Cancer Center
Belleville, New Jersey, United States, 07103
St. Joseph's Hospital and Medical Center
Paterson, New Jersey, United States, 07503
United States, Pennsylvania
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
Investigators
Study Chair: Jack D. Burton, MD Garden State Cancer Center at the Center for Molecular Medicine and Immunology
  More Information

Additional Information:
No publications provided

Responsible Party: Robert M Sharkey, GSCC
ClinicalTrials.gov Identifier: NCT00004085     History of Changes
Other Study ID Numbers: CDR0000067297, R35CA039841, CMMI-C-041A-98, NCI-H99-0039, NCI-V99-1568
Study First Received: December 10, 1999
Last Updated: June 21, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Garden State Cancer Center at the Center for Molecular Medicine and Immunology:
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Antibodies
Antibodies, Monoclonal
Lenograstim
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on April 17, 2014