Clinical trial NCT00009763: Monoclonal Antibody Therapy, Cyclosporine, and Paclitaxel in Treating Patients With Recurrent or Refractory Metastatic Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Breast Cancer
Keywords: stage IV breast cancer
recurrent 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: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with cyclosporine and paclitaxel may be an effective treatment for metastatic breast cancer.

PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy, cyclosporine, and paclitaxel in treating patients who have recurrent or refractory metastatic breast cancer.

Detailed description: OBJECTIVES:

* 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.
* Determine the preliminary efficacy of this regimen in these patients.

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.

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

Eligibility 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

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/mm\^3
* Platelet count at least 100,000/mm\^3

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

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)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
Study officials:
affiliation: University of California, Davis
name: Carol M. Richman, MD
role: STUDY_CHAIR
References: