Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Monoclonal Antibody Therapy, Cyclosporine, and Paclitaxel in Treating Patients With Recurrent or Refractory Metastatic Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over Other UCD-992080 NCI-V00-1640, NCT00009763

Objectives

1. Determine the maximum tolerated dose of yttrium Y 90 monoclonal antibody m170 in combination with cyclosporine and paclitaxel in patients with recurrent or refractory metastatic breast cancer.
2. Determine the preliminary efficacy of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed metastatic breast adenocarcinoma
  • Residual or recurrent disease after first-line standard chemotherapy
  • Clinical evidence of metastatic disease



• Tumor cells positive for m170 immunoreactivity



• HAMA titer negative



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy:

• See Chemotherapy

Chemotherapy:

• See Disease Characteristics
• At least 1 prior chemotherapy regimen for advanced disease
• Prior high-dose chemotherapy with autologous stem cell transplantation is allowed if given at least 12 months prior to study and carmustine was not used
• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior external beam radiotherapy
• No prior radiotherapy to more than 25% of the total skeleton

Surgery:

• Not specified

Other:

• No requirement for oral anticoagulants (low-dose warfarin for central line thrombosis prophylaxis allowed)

Patient Characteristics:

Age:

• 18 and over

Sex:

• Not specified

Menopausal status:

• Not specified

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• Neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin no greater than 1.5 mg/dL

Renal:

• Creatinine less than 1.5 mg/dL

Cardiovascular:

• LVEF at least 50% by MUGA

Pulmonary:

• FEV1 at least 65% of predicted
• FVC at least 65% of predicted
• DLCO at least 60%

Other:

• No other malignancy within the past 5 years except nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

A total of 18-30 patients will be accrued for this study within 36 months.

Outline

This is a dose-escalation study of yttrium Y 90 monoclonal antibody m170 (Y90 MOAB m170).

Patients receive filgrastim (G-CSF) subcutaneously (SC) daily for 4 days prior to apheresis which continues daily for a maximum of 5 days. A minimum of 6 million CD34+ cells/kg must be harvested.

Patients receive oral cyclosporine every 12 hours on days -3 to 25. Patients receive unlabeled monoclonal antibody (MOAB) m170 IV followed by a tracer dose of indium In 111 MOAB m170 IV on day 0. On day 7, patients receive unlabeled MOAB m170 IV followed by Y90 MOAB m170 IV. Patients in cohorts 2-4 also receive paclitaxel IV over 3 hours on day 9.

If needed, patients undergo autologous peripheral blood stem cell transplantation on day 21 and receive G-CSF SC daily until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of Y90 MOAB m170 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 toxicity.

Patients are followed monthly for 3 months, every 3 months for 1 year, and then every 6 months for 1 year.

Trial Contact Information

Trial Lead Organizations

University of California Davis Cancer Center

Carol Richman, MD, Protocol chair		Ph: 916-734-3771 Email: carol.richman@ucdmc.ucdavis.edu

Registry Information
Official Title		Combined Modality Radioimmunotherapy For Metastatic Breast Adenocarcinoma With Two Cycles Of Escalating Dose 90Y-DOTA-peptide-m170 and Fixed, Low Dose Paclitaxel With Blood Stem Cell Support And Cyclosporin For HAMA Suppression
Trial Start Date		2001-03-27
Registered in ClinicalTrials.gov		NCT00009763
Date Submitted to PDQ		2000-11-13
Information Last Verified		2003-11-24