Iodine I 131 Monoclonal Antibody 8H9 in Treating Patients with Desmoplastic Small Round Cell Tumors and Other Solid Tumors Involving the Peritoneum

This phase I trial studies the side effects and best dose of iodine I 131 monoclonal antibody 8H9 in treating patients with small round cell tumors that cause or form adhesions or fibrous connective tissue within a tumor (desmoplastic) and other solid tumors involving the peritoneum. Radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody 8H9, can find tumor cells and carry tumor-killing substances to them without harming normal cells.

Inclusion Criteria

• Patients must have the diagnosis of (a) DSRCT with peritoneal involvement or (b) other 8H9-positive solid tumors involving the peritoneum (e.g. adrenocortical carcinoma, Wilm's tumor)
• For tumors other than DSRCT, patients must have a history of tumor progression or recurrence or failure to achieve complete response with standard therapy or < 20% chance of long term disease-free survival
• For tumors other than DSRCT, 8H9 reactivity must be confirmed by immunohistochemistry
• Patients with DSCRT are not required to have measurable or evaluable disease
• Patients with tumors other than DSRCT without measurable or evaluable disease will only be considered if they have < 20% chance of long term disease-free survival
• Prior therapy: at least 4 weeks should have elapsed since any biologic therapy, or immunotherapy; three weeks should have elapsed since last dose of chemotherapy or radiotherapy
• Able to cooperate with radiation safety restrictions during therapy period
• Stem cells: patients must have an autologous hematopoietic stem cell product cryopreserved and available for re-infusion after 131I-8H9 treatment; the minimum dose for hematopoietic stem cells is 2 x 10^6 cluster of differentiation (CD)34+ cells/kg
• Minimum life expectancy of six weeks as determined by consenting professional
• Signed informed consent indicating awareness of the investigational nature of this program

Exclusion Criteria

• Severe major organ toxicity; renal, cardiac, hepatic, pulmonary, gastrointestinal and neurologic toxicity should all be grade 1 or less (per National Cancer Institute [NCI] Common Toxicity Criteria [CTC] version 3 criteria) with the following exceptions: * Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase should be =< 5 x upper limit of normal (ULN) * Serum bilirubin =< 3 x ULN and nausea and vomiting should be =< grade 2 * Patients with myelosuppression are not excluded if absolute neutrophil count (ANC) >= 500/uL
• Platelet count should be > 50,000/ul and hemoglobin should be > 8 gm/dl; patients may receive platelet or red blood cell transfusions to maintain hemoglobin and platelets at clinical appropriate levels
• Patients with clinically suspected dense intraperitoneal adhesions preventing adequate IP distribution
• History of allergy to mouse proteins
• Patients previously treated with murine monoclonal antibodies will be excluded if they have a human anti-murine antibody (HAMA) level of > 1000 U/ml
• Active serious infections not controlled by antibiotics
• Pregnant women and women who are breast feeding are excluded; negative pregnancy test is required for all women of child-bearing age, and appropriate contraception is used during the study period; pregnancy testing will be carried out within two weeks prior to administration of radioiodinated 8H9 in females of childbearing age
• Inability or unwillingness to comply with radiation safety procedures or protocol requirements

PRIMARY OBJECTIVES:

I. Define the toxicity and maximal tolerated dose (MTD) of iodine I 131 monoclonal antibody 8H9 (131I-8H9) administered intraperitoneally.

SECONDARY OBJECTIVES:

I. Assess pharmacokinetics for intraperitoneal (IP) 131I-8H9.

II. Assess response of desmoplastic small round cell tumor (DSRCT) and other solid tumors to IP 131I-8H9.

OUTLINE: This is a dose-escalation study.

Patients receive iodine I 131 monoclonal antibody 8H9 IP on day 0.

After completion of study treatment, patients are followed up periodically.

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Shakeel Modak

Primary ID 09-090
Secondary IDs NCI-2010-01242
Clinicaltrials.gov ID NCT01099644