Phase I/II Radioimmunotherapy With High-Dose 90Y-Labeled Humanized MN-14 Alone or Combined With Doxorubicin and Peripheral Blood Stem Cell Rescue (PBSCR) in Medullary Thyroid Cancer (MTC) Grant Application Title: Radioimmunotherapy of MTC With Y-90 Humanized MN14 Anti-CEA Mab and Doxorubicin
OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicities of high
dose yttrium Y 90 monoclonal antibody MN-14 with or without doxorubicin plus peripheral
blood stem cell rescue in patients with medullary thyroid cancer. II. Correlate organ and
tumor dosimetry with toxicity and antitumor responses in these patients. III. Assess
response and duration of response in these patients after this treatment.
OUTLINE: This is a dose escalation study of yttrrium Y 90 monoclonal antibody MN-14
(90Y-MN-14). Patients are stratified by prior doxorubicin (yes vs no). Patients receive
filgrastim (G-CSF) subcutaneously (SQ) on days -11 to -7 and undergo leukapheresis on days
-8 to -6. 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 (In111-MN-14) on day 0. At least 1 confirmed tumor site must be targeted.
Patients receive 90Y-MN-14 IV over 30-45 minutes on day 7. Some patients also receive
doxorubicin IV on day 8. PBSC or bone marrow is reinfused on approximately day 7-14.
Patients also receive G-CSF SQ or IV until blood counts recover. Cohorts of 3-6 patients
receive escalating radiological doses of 90Y-MN-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, kidneys, and
liver. Patients are followed weekly for the first month, monthly for 3 months, then every 6
months for up to 5 years.
PROJECTED ACCRUAL: Approximately 30 patients will be accrued for each stratum of this study
within 3 years.
Primary Purpose: Treatment
Jack D. Burton, MD
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
United States: Food and Drug Administration
|St. Joseph's Hospital and Medical Center||Paterson, New Jersey 07503|
|Garden State Cancer Center||Belleville, New Jersey 07103|