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

NCT ID: NCT00004048

Last Updated: 2011-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-09-30
• Study Completion Date: 2002-05-31

Brief Summary

RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and deliver tumor-killing substances to them without harming normal cells. Chemotherapy uses different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by radioimmunotherapy or chemotherapy used to kill tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of radioimmunotherapy with or without doxorubicin plus peripheral stem cell transplantation in treating patients who have thyroid cancer.

Detailed Description

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.

Conditions

Head and Neck Cancer

Study Design

• Primary Study Purpose: TREATMENT

Interventions

filgrastim

Intervention Type: BIOLOGICAL

doxorubicin hydrochloride

Intervention Type: DRUG

autologous bone marrow transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

indium In 111 monoclonal antibody MN-14

Intervention Type: RADIATION

yttrium Y 90 monoclonal antibody MN-14

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: lead

Responsible Party

Garden State Cancer Center

Principal Investigators

Jack D. Burton, MD

Role: STUDY_CHAIR

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

Locations

Garden State Cancer Center

Belleville, New Jersey, United States

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States

Countries

United States

Other Identifiers

CMMI-C-040A-98

Identifier Type: -

Identifier Source: secondary_id

CMMI-FDR001555

Identifier Type: -

Identifier Source: secondary_id

NCI-V99-1564

Identifier Type: -

Identifier Source: secondary_id

CDR0000067172

Identifier Type: -

Identifier Source: org_study_id