Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Radioimmunotherapy With or Without Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Thyroid Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed 16 to 80 Other CMMI-C-040A-98 CMMI-FDR001555, NCI-V99-1564, NCT00004048

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.

Entry 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

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

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

Expected Enrollment

Approximately 30 patients will be accrued for each stratum of this study 
within 3 years.

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.

Trial Contact Information

Trial Lead Organizations

Garden State Cancer Center

Jack Burton, MD, Protocol chair		Ph: 973-844-7024 Email: jburton@gscancer.org

Registry Information
Official Title		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
Trial Start Date		1998-09-02
Registered in ClinicalTrials.gov		NCT00004048
Date Submitted to PDQ		1999-06-30
Information Last Verified		2001-10-01