Radiolabeled Monoclonal Antibody Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory or Recurrent Ovarian Epithelial Cancer

Study Description

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Brief Summary:

RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by therapy used to kill tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of radiolabeled monoclonal antibody plus peripheral stem cell transplantation in treating patients who have refractory or recurrent ovarian epithelial cancer.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer	Biological: filgrastim; Procedure: peripheral blood stem cell transplantation; Radiation: indium In 111 monoclonal antibody MN-14; Radiation: yttrium Y 90 monoclonal antibody MN-14	Phase 1; Phase 2

Detailed Description:

OBJECTIVES: I. Determine the normal organ and tumor dosimetry with yttrium Y 90 monoclonal antibody MN-14 using indium In 111 monoclonal antibody MN-14 as pretherapy in patients with advanced ovarian epithelial cancer. II. Evaluate the extent and duration of antitumor response in these patients on this regimen.

OUTLINE: This is a dose escalation study of yttrium Y 90 monoclonal antibody MN-14 (90Y hMN-14). Patients receive filgrastim (G-CSF) subcutaneously (SQ) on days -17 to -13, followed by leukapheresis on days -14 to -12. 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 over 30 minutes on day -7. At least 1 confirmed tumor site must be targeted. Patients receive 90Y hMN-14 IV over 30-45 minutes on day 0. PBSC is reinfused within 7 to 14 days after 90 hMN-14 administration. Patients receive G-CSF SQ or IV until blood counts recover. Cohorts of 3-6 patients receive escalating doses of 90Y hMN-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, kidney, and liver are reached. Patients are followed weekly for 1 month, every 2 weeks for 2 months, monthly for 3 months, every 3 months for 2 years, and then every 6 months for 5 years.

PROJECTED ACCRUAL: Approximately 48-51 patients will be accrued for this study within 5 years.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	15 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase I/II Radioimmunotherapy With High-Dose 90Y-Labeled Humanized MN-14 in Advanced Ovarian Cancer Using Autologous Peripheral Blood Stem Cell Rescue (PBSCR) to Control Myelotoxicity
Study Start Date :	August 1999
Actual Primary Completion Date :	May 2002

Arms and Interventions

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Intervention Details:

Biological: filgrastim
as prescribed by physician
Procedure: peripheral blood stem cell transplantation
1-2 weeks from treatment
Radiation: indium In 111 monoclonal antibody MN-14
intravenous infusion over 30 min; single dose
Radiation: yttrium Y 90 monoclonal antibody MN-14
intravenous infusion over 30 min; single dose

Outcome Measures

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Primary Outcome Measures :

1. maximum tolerated dose [ Time Frame: 12 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically refractory or recurrent ovarian epithelial cancer Resistant to platinum or taxane containing chemotherapy within past 6 months Autologous peripheral blood stem cells (PBSC) or bone marrow available At least 1 measurable site confirmed by CT targeted pretherapy indium In 111 monoclonal antibody MN-14 imaging No bone marrow involvement

PATIENT CHARACTERISTICS: Age: 18 to 80 Performance status: Karnofsky 70-100% ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: WBC at least 3,000/mm3 Granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT less than 2.0 times upper limit of normal (ULN) Renal: Creatinine less than 1.5 times ULN Creatinine clearance at least 50 mL/min Cardiovascular: LVEF at least 50% by MUGA Pulmonary: FVC, FEV1, and DLCO at least 70% of predicted Other: Not pregnant Fertile patients must use effective contraception during and for 3 months after study No AIDS-related illness No concurrent significant medical complications that would preclude compliance No severe anorexia, nausea, or vomiting No history of allergy or antibodies to 90Y hMN-14

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior imaging studies with murine monoclonal antibodies showing reactivity with yttrium Y 90 monoclonal antibody MN-14 (90Y hMN-14) Chemotherapy: At least 4 weeks since prior chemotherapy and recovered Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy to index lesion and recovered No prior radiotherapy to greater than 25% of red marrow No prior radiotherapy to maximum tolerated levels for any critical organ (e.g., lung, liver, or kidney) Surgery: At least 4 weeks since prior major surgery Other: No concurrent antiretroviral medication

Contacts and Locations

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Locations

United States, New Jersey
Garden State Cancer Center
Belleville, New Jersey, United States, 07103
St. Joseph's Hospital and Medical Center
Paterson, New Jersey, United States, 07503
United States, Pennsylvania
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

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

National Cancer Institute (NCI)

Investigators

Study Chair:	Jack D. Burton, MD	Garden State Cancer Center at the Center for Molecular Medicine and Immunology

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Robert M Sharkey, GSCC
ClinicalTrials.gov Identifier:	NCT00004177 History of Changes
Other Study ID Numbers:	CDR0000067299; R03CA077146 ( U.S. NIH Grant/Contract ); CMMI-C-039A-98; NCI-H99-0044; NCI-V99-1570
First Posted:	April 16, 2004
Last Update Posted:	June 22, 2011
Last Verified:	June 2011

Keywords provided by Garden State Cancer Center at the Center for Molecular Medicine and Immunology:

recurrent ovarian epithelial cancer

Additional relevant MeSH terms:

Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female	Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs