Pharmacokinetic/Dosimetry/MTNTD Study of 111In/90Y-2IT-BAD-m170 for Therapy in Metastatic Breast Cancer Patients With Post Therapy Support of Autologous Pretherapy Apheresed Peripheral Blood Stem Cells and Cyclosporin A Given for Suppression of HAMA Response
18 Years
55 Years
Both
Breast Cancer
Trial Information
Pharmacokinetic/Dosimetry/MTNTD Study of 111In/90Y-2IT-BAD-m170 for Therapy in Metastatic Breast Cancer Patients With Post Therapy Support of Autologous Pretherapy Apheresed Peripheral Blood Stem Cells and Cyclosporin A Given for Suppression of HAMA Response
OBJECTIVES: I. Determine variation in indium In 111 labeled 2IT-BAD monoclonal antibody 170
(111In-2IT-BAD-m170) pharmacokinetics before and with each therapy in patients with
metastatic breast cancer. II. Determine each therapeutic dose of yttrium Y 90 labeled
2IT-BAD monoclonal antibody 170 (90Y-2IT-BAD-m170) based on the calculated radiation
dosimetry for normal nonmarrow tissues from the pharmacokinetic study with
111In-2IT-BAD-m170 performed prior to each therapy course in these patients. III. Determine
the maximum tolerated, nonmarrow, normal tissue dose (MTNTD) of 90Y-2IT-BAD-m170 for these
patients when up to 3 courses with cyclosporine plus autologous peripheral stem cell support
are given every 3 months. IV. Evaluate the safety of and tumor response to
111In/90Y-2IT-BAD-m170 therapy with cyclosporine and autologous peripheral stem cells at the
MTNTD in these patients.
OUTLINE: This is a dose escalation study of yttrium Y 90 labeled 2IT-BAD monoclonal antibody
170 (90Y-2IT-BAD-m170). Patients are stratified according to risk based on prior therapy
(standard combined chemotherapy vs standard and high dose combined chemotherapy with bone
marrow transplant or stem cell support). All patients receive subcutaneous filgrastim
(G-CSF) during stem cell collection. Beginning 3 to 5 days after starting G-CSF, patients
undergo apheresis either daily or every other day for 4 to 8 procedures. Patients receive
oral cyclosporine twice daily, starting on day 1, for up to 2 weeks. On day 4, patients
receive nonlabeled 2IT-BAD monoclonal antibody m170 IV over 10-15 minutes, followed 15
minutes later by indium In 111 labeled 2IT-BAD monoclonal antibody 170 (111In-2IT-BAD-m170)
IV over 10-15 minutes. Patients then undergo dosimetry imaging immediately, again 3 hours
later, and then on days 1-4 and day 7 postinjection. Patients receive nonlabeled monoclonal
antibody IV over 10-15 minutes, followed 15 minutes later by In 111/Y 90 labeled 2IT-BAD
monoclonal antibody 170 (111In/90Y-2IT-BAD-m170) IV over 10-15 minutes, then undergo imaging
as in pretherapy. Patients also receive cyclosporine, administered as in pretherapy, for a
total of 35 days, plus autologous stem cell support followed by G-CSF after each course.
Cohorts of 3-9 patients receive escalating doses of 111In/90Y-2IT-BAD-m170. Patients proceed
to the next dose level if 3 or more patients in the same or higher risk group have not
reached the maximum tolerated, nonmarrow, normal tissue dose (MTNTD) at least 3 months after
the second course of therapy. Therapy repeats every 3 months for 3 courses.
PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically confirmed refractory metastatic breast cancer Must
have either relapsed or failed to achieve complete remission after combination
chemotherapy with or without stem cell or marrow transplantation No CNS disease No
generalized or total mass liver involvement greater than 25% volume No pulmonary
metastasis involving greater than 25% of lung volume Tumor markers and evidence of
metastatic disease by physical exam or radiography required for patients with bone disease
only Hormone receptor status: Not specified
PATIENT CHARACTERISTICS: Age: 18 to physiologic age of 55 Menopausal status: Not specified
Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic:
Absolute granulocyte count at least 2000/mm3 Platelet count at least 150,000/mm3 Arterial
blood gases within normal limits for age and sex Hepatic: See Disease Characteristics
Bilirubin no greater than 1.3 mg/dL Renal: Creatinine no greater than 1.5 mg/dL
Cardiovascular: LVEF at least 50% by MUGA Pulmonary: FEV1 and FVC at least 65% of
predicted Corrected diffusing capacity at least 60% Other: Adequate venous access Able to
tolerate apheresis, filgrastim (G-CSF), and cyclosporine Human anti-mouse antibody (HAMA)
negative No other primary malignant neoplasm except curatively treated basal cell
carcinoma or surgically cured 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 Disease Characteristics Chemotherapy: See
Disease Characteristics At least 4 weeks since prior chemotherapy No concurrent
chemotherapy At least 1 year since prior high dose intensive marrow toxic therapy
requiring stem cells or bone marrow transplantation No pulmonary toxicity due to prior
chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior
radiotherapy No concurrent radiotherapy No prior radiotherapy to greater than 25% of total
skeleton Surgery: Not specified
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Sally DeNardo, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of California, Davis
Authority:
United States: Federal Government
Study ID:
CDR0000067105
NCT ID:
NCT00003920
Start Date:
April 1996
Completion Date:
Related Keywords:
- Breast Cancer
- stage IV breast cancer
- recurrent breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| University of California Davis Medical Center | Sacramento, California 95817 |
