Clinical trial NCT00007891: Radiolabeled Monoclonal Antibody Therapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Metastatic Breast Cancer
Official title: Phase I Study of 90-Y-Humanized-BrE-3 Followed by Autologous Hematopoietic Progenitor Cell Support in Patients With Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Keywords: stage IV breast cancer
recurrent breast cancer
male breast cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Peripheral stem cell transplantation or bone marrow transplantation may be able to replace immune cells that were destroyed by monoclonal antibody therapy used to kill tumor cells.

PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy followed by bone marrow or peripheral stem cell transplantation in treating patients who have metastatic breast cancer.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose of yttrium Y 90 labeled, humanized monoclonal antibody BrE-3 when given in combination with indium In 111 labeled, humanized monoclonal antibody BrE-3 followed by autologous bone marrow or peripheral blood stem cell transplantation in patients with metastatic breast cancer.
* Determine hematopoietic engraftment in these patients treated with this regimen.
* Determine the ability of indium In 111 labeled, humanized monoclonal antibody BrE-3 to image metastatic disease in these patients.
* Determine the pharmacokinetics of this regimen in these patients.
* Determine the preliminary antitumor response in these patients treated with this regimen.

OUTLINE: This is a dose escalation study of yttrium Y 90 labeled, humanized monoclonal antibody BrE-3 (Y90 huMOAB BrE-3).

Patients receive Y90 huMOAB BrE-3 and indium In 111 labeled, humanized monoclonal antibody BrE-3 IV over 1-2 hours on day -14. Patients undergo autologous bone marrow or peripheral blood stem cell transplantation on day 0. Patients also receive filgrastim (G-CSF) IV beginning on day 0 and continuing until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of Y90 huMOAB BrE-3 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicities.

Patients are followed every 3-4 months for 1 year and then at least annually thereafter.

PROJECTED ACCRUAL: Approximately 3-30 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed metastatic breast cancer

  * BrE-3 positive
  * Relapsed or refractory disease with tumor progression after effective therapy allowed
* Measurable or evaluable disease
* Received at least one prior chemotherapy regimen for metastatic disease and have at least one of the following:

  * Chemotherapy refractory liver metastases more than 2 cm
  * Multiple non-resectable liver metastases
  * Brain metastases
  * Prior high-dose chemotherapy
  * Relapse within prior radiotherapy field
* Hormone receptor status:

  * Not specified

PATIENT CHARACTERISTICS:

Age:

* Over 18

Sex:

* Male or female

Menopausal status:

* Not specified

Performance status:

* 0-1

Life expectancy:

* Not specified

Hematopoietic:

* WBC greater than 3,000/mm3
* Absolute neutrophil count greater than 1,000/mm3
* Platelet count greater than 100,000/mm3

Hepatic:

* Bilirubin less than 2 times normal
* SGOT/SGPT less than 2 times normal

Renal:

* Creatinine clearance greater than 60 mL/min

Cardiovascular:

* LVEF greater than 45% by MUGA scan

Pulmonary:

* DLCO and FEV 1.0 greater than 60% predicted

Other:

* Not pregnant
* Negative pregnancy test
* Fertile patients must use effective contraception
* No known hypersensitivity to E. coli derived proteins
* No other comorbid condition that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior high-dose chemotherapy with autologous peripheral blood stem cell transplantation

Chemotherapy:

* See Disease Characteristics
* See Biologic therapy

Endocrine therapy:

* Not specified

Radiotherapy:

* See Disease Characteristics

Surgery:

* Not specified

Other:

* Recovered from prior therapy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Cancer Research Institute of Contra Costa
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at University of Colorado Health Sciences Center
state: Colorado
Study officials:
affiliation: Cancer Research Institute of Contra Costa
name: Roberto L. Ceriani, MD, PhD
role: STUDY_CHAIR
References: