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
16 Years
80 Years
Both
Head and Neck Cancer
Trial Information
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.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically proven medullary thyroid
carcinoma Unresectable local-regional disease OR Distant metastases Autologous peripheral
blood stem cells (PBSC) or bone marrow available Diffuse bone/marrow involvement allowed
if: Autologous bone marrow or PBSC with no greater than 5% tumor involvement available
Radiation dose to marrow no greater than 3000 cGy until 6 patients have been treated
safely at that dose level At least 1 site confirmed by CT targeted by pretherapy indium In
111 monoclonal antibody MN-14 imaging
PATIENT CHARACTERISTICS: Age: 16 to 80 Performance status: Karnofsky 60-100% ECOG 0-2 Life
expectancy: At least 3 months Hematopoietic: WBC at least 3000/mm3 Granulocyte count at
least 1500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 2
mg/dL Renal: Creatinine less than 1.5 times upper limit of normal Cardiovascular: Ejection
fraction at least 50% Other: No severe anorexia, nausea, or vomiting No concurrent
significant medical complications that would preclude compliance Not pregnant Fertile
patients must use effective contraception during and for 3 months after study
PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since biologic therapy
Chemotherapy: At least 4 weeks since prior chemotherapy and recovered No greater than 240
mg/m2 doxorubicin total for combination therapy with doxorubicin but no greater than 550
mg/m2 doxorubicin if radioimmunotherapy alone No prior failure on doxorubicin therapy for
combination therapy but not radioimmunotherapy alone Endocrine therapy: Prior synthroid
(T4) allowed Radiotherapy: See Disease Characteristics At least 4 weeks since prior
radiotherapy to index lesion and recovered No prior radiotherapy to greater than 35% of
red marrow Surgery: At least 4 weeks since prior major surgery
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
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:
CDR0000067172
NCT ID:
NCT00004048
Start Date:
September 1998
Completion Date:
May 2002
Related Keywords:
- Head and Neck Cancer
- thyroid gland medullary carcinoma
- Thyroid Neoplasms
- Head and Neck Neoplasms
Name | Location |
|---|---|
| St. Joseph's Hospital and Medical Center | Paterson, New Jersey 07503 |
| Garden State Cancer Center | Belleville, New Jersey 07103 |
