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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


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Breast Cancer

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety

Outcome Description:

maximum tolerated dose

Outcome Time Frame:

12 weeks

Safety Issue:

No

Principal Investigator

Jack D. Burton, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Garden State Cancer Center at the Center for Molecular Medicine and Immunology

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000067297

NCT ID:

NCT00004085

Start Date:

May 1998

Completion Date:

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms

Name

Location

University of Pennsylvania Cancer CenterPhiladelphia, Pennsylvania  19104
St. Joseph's Hospital and Medical CenterPaterson, New Jersey  07503
Garden State Cancer CenterBelleville, New Jersey  07103