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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004177
• Other study ID #: CDR0000067299
• Secondary ID: R03CA077146CMMI-
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 21, 2000
• Last updated: June 21, 2011
• Start date: August 1999

Study information

• Verified date: June 2011
• Source: Garden State Cancer Center at the Center for Molecular Medicine and Immunology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. primary completion date: May 2002
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

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
• yttrium Y 90 monoclonal antibody MN-14
intravenous infusion over 30 min; single dose

Locations

Country	Name	City	State
United States	Garden State Cancer Center	Belleville	New Jersey
United States	St. Joseph's Hospital and Medical Center	Paterson	New Jersey
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Garden State Cancer Center at the Center for Molecular Medicine and Immunology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maximum tolerated dose		12 weeks	No