Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
New York University School of Medicine
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00089245
First received: August 4, 2004
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to find a safe dose of a new medicine called antibody 8H9. Antibodies are made by the body to fight infections and in some cases, to fight tumors. The antibody 8H9 is made by mice and can attack many kinds of tumors. 8H9 antibody can have a dose of radiation attached to it called 131-I. 131I-8H9 has been given in the vein to patients to find cancer cells. This is the first study using 131I-8H9 in the fluid in the spine to kill cancer cells. 131-I is a beta emitting isotope used extensively for radiation targeted therapies.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Neuroblastoma
Sarcoma
Radiation: iodine I 131 monoclonal antibody 8H9
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study Of Intrathecal Radioimmunotherapy Using I-8H9 For Central Nervous System/Leptomeningeal Neoplasms

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • to evaluate the Maximally Tolerated Dose (MTD) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    In order to find the MTD, a dose escalation scheme will be employed with patients entering in cohorts of 3 at each dose level from 10 mCi to 60 mCi and a cohort of 6 at each dose level from 70 mCi to 100 mCi. Dose escalation is based on the Dose Limiting Toxicity (DLT), which is defined as grade 3 or 4 neurotoxicity clearly related to 8H9 (excluding headache, fever, vomiting, hyperglycemia, lymphopenia and anemia).


Estimated Enrollment: 120
Study Start Date: July 2004
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Radiolabeled Monoclonal Antibody Therapy
This is a Phase I trial designed to evaluate the Maximally Tolerated Dose (MTD) of intrathecal 131I-8H9. In order to find the MTD, a dose escalation scheme will be employed with patients entering in cohorts of 3 at each dose level from 10 mCi to 60 mCi and a cohort of 6 at each dose level from 70 mCi to 100 mCi.
Radiation: iodine I 131 monoclonal antibody 8H9

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Subject Inclusion Criteria:

  • Patients must have a histologically confirmed diagnosis of a malignancy known to be 8H9 reactive. 8H9 expression must be confirmed by immunohistochemical staining of tumor and assessed by the Department of Pathology or by immunofluorescence of bone marrow except for patients confirmed to have neuroblastoma.
  • Patients must have CNS/ leptomeningeal disease which is refractory to conventional therapies or for which no conventional therapy exists OR a recurrent brain tumors with a predilection for leptomeningeal dissemination (medulloblastoma, PNET, rhabdoid tumor).
  • Patients must have no rapidly progressing or deteriorating neurologic examination.
  • Patients must have an absolute neutrophil count (ANC) > 1000/ul and a platelet count > 50,000/ul.
  • Patients may have active malignancy outside the central nervous system.
  • Both pediatric and adult patients of any age are eligible.
  • Patients or a legal guardian will sign an informed consent form approved by the IRB and obtained by the Principal or a Co- Investigator before patient entry. Minors will provide assent.
  • Patients with stored stem cells will be treated at the escalating dose while patients with no stem cells will be treated at the 50 mCi dose. Neuroblastoma patients can be treated at the 50 mCi dose with or without stored stem cells.

Subject Exclusion Criteria:

  • Patients with obstructive or symptomatic communicating hydrocephalus.
  • Patients with an uncontrolled life-threatening infection.
  • Patients who are pregnant: Pregnant women are excluded for fear of danger to the fetus. Therefore negative pregnancy test is required for all women of child-bearing age, and appropriate contraception is required during the study period.
  • Patients who have received cranial or spinal irradiation less than 3 weeks prior to the start of this protocol.
  • Patients who have received systemic chemotherapy (corticosteroids not included) less than 3 weeks prior to the start of this protocol.
  • Severe major organ toxicity. Specifically, renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity should all be less than grade 2. Patients with stable neurological deficits (because of their brain tumor) are not excluded. Patients with <= 3 hearing loss are not excluded.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00089245

Contacts
Contact: Kim Kramer 212-639-6410
Contact: Nai-Kong Cheung, MD, PhD 646-888-2313

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Kim Kramer, MD    212-639-6410      
Contact: Nai-Kong Cheung, MD, PhD    646-888-2313      
Principal Investigator: Kim Kramer, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
New York University School of Medicine
Investigators
Principal Investigator: Kim Kramer, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00089245     History of Changes
Other Study ID Numbers: 03-133, P30CA008748, MSKCC-03133
Study First Received: August 4, 2004
Last Updated: May 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
leptomeningeal metastases
recurrent neuroblastoma
disseminated neuroblastoma
recurrent adult brain tumor
recurrent childhood medulloblastoma
recurrent childhood rhabdomyosarcoma
recurrent childhood soft tissue sarcoma
recurrent osteosarcoma
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
childhood atypical teratoid/rhabdoid tumor
adult medulloblastoma
previously treated childhood rhabdomyosarcoma
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
metastatic osteosarcoma
childhood desmoplastic small round cell tumor
metastatic childhood soft tissue sarcoma
adult rhabdomyosarcoma
recurrent adult soft tissue sarcoma
stage IV adult soft tissue sarcoma

Additional relevant MeSH terms:
Nervous System Neoplasms
Neuroblastoma
Central Nervous System Neoplasms
Neuroectodermal Tumors, Primitive, Peripheral
Meningeal Neoplasms
Sarcoma
Neoplasms by Site
Neoplasms
Nervous System Diseases
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Connective and Soft Tissue
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014