Phase I/II Radioimmunotherapy With High-Dose 90Y-Labeled Humanized MN-14 in Advanced Ovarian Cancer Using Autologous Peripheral Blood Stem Cell Rescue (PBSCR) to Control Myelotoxicity
18 Years
80 Years
Female
Ovarian Cancer
Trial Information
Phase I/II Radioimmunotherapy With High-Dose 90Y-Labeled Humanized MN-14 in Advanced Ovarian Cancer Using Autologous Peripheral Blood Stem Cell Rescue (PBSCR) to Control Myelotoxicity
OBJECTIVES: I. Determine the normal organ and tumor dosimetry with yttrium Y 90 monoclonal
antibody MN-14 using indium In 111 monoclonal antibody MN-14 as pretherapy in patients with
advanced ovarian epithelial cancer. II. Evaluate the extent and duration of antitumor
response in these patients on this regimen.
OUTLINE: This is a dose escalation study of yttrium Y 90 monoclonal antibody MN-14 (90Y
hMN-14). Patients receive filgrastim (G-CSF) subcutaneously (SQ) on days -17 to -13,
followed by leukapheresis on days -14 to -12. If an adequate number of CD34+ cells are not
harvested, bone marrow is also collected. Patients receive pretherapy targeting consisting
of indium In 111 monoclonal antibody MN-14 over 30 minutes on day -7. At least 1 confirmed
tumor site must be targeted. Patients receive 90Y hMN-14 IV over 30-45 minutes on day 0.
PBSC is reinfused within 7 to 14 days after 90 hMN-14 administration. Patients receive G-CSF
SQ or IV until blood counts recover. Cohorts of 3-6 patients receive escalating doses of 90Y
hMN-14 until the maximum tolerated dose (MTD) is determined. The MTD is defined as either
the dose at which no more than 1 of 6 patients experiences dose limiting toxicity or the
threshold radiation doses to lungs, kidney, and liver are reached. Patients are followed
weekly for 1 month, every 2 weeks for 2 months, monthly for 3 months, every 3 months for 2
years, and then every 6 months for 5 years.
PROJECTED ACCRUAL: Approximately 48-51 patients will be accrued for this study within 5
years.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically refractory or recurrent ovarian
epithelial cancer Resistant to platinum or taxane containing chemotherapy within past 6
months Autologous peripheral blood stem cells (PBSC) or bone marrow available At least 1
measurable site confirmed by CT targeted pretherapy indium In 111 monoclonal antibody
MN-14 imaging No bone marrow involvement
PATIENT CHARACTERISTICS: Age: 18 to 80 Performance status: Karnofsky 70-100% 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 no greater than 2.0
mg/dL SGOT less than 2.0 times upper limit of normal (ULN) Renal: Creatinine less than 1.5
times ULN Creatinine clearance at least 50 mL/min Cardiovascular: LVEF at least 50% by
MUGA Pulmonary: FVC, FEV1, and DLCO at least 70% of predicted Other: Not pregnant Fertile
patients must use effective contraception during and for 3 months after study No
AIDS-related illness No concurrent significant medical complications that would preclude
compliance No severe anorexia, nausea, or vomiting No history of allergy or antibodies to
90Y hMN-14
PRIOR CONCURRENT THERAPY: Biologic therapy: No prior imaging studies with murine
monoclonal antibodies showing reactivity with yttrium Y 90 monoclonal antibody MN-14 (90Y
hMN-14) Chemotherapy: At least 4 weeks since prior chemotherapy and recovered Endocrine
therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy to index
lesion and recovered No prior radiotherapy to greater than 25% of red marrow No prior
radiotherapy to maximum tolerated levels for any critical organ (e.g., lung, liver, or
kidney) Surgery: At least 4 weeks since prior major surgery Other: No concurrent
antiretroviral medication
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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:
CDR0000067299
NCT ID:
NCT00004177
Start Date:
August 1999
Completion Date:
Related Keywords:
- Ovarian Cancer
- recurrent ovarian epithelial cancer
- Ovarian Neoplasms
- Neoplasms, Glandular and Epithelial
Name | Location |
|---|---|
| University of Pennsylvania Cancer Center | Philadelphia, Pennsylvania 19104 |
| St. Joseph's Hospital and Medical Center | Paterson, New Jersey 07503 |
| Garden State Cancer Center | Belleville, New Jersey 07103 |
