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

Primary Purpose

Ovarian Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
filgrastim
peripheral blood stem cell transplantation
indium In 111 monoclonal antibody MN-14
yttrium Y 90 monoclonal antibody MN-14
Sponsored by
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring recurrent ovarian epithelial cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Garden State Cancer Center
  • St. Joseph's Hospital and Medical Center
  • University of Pennsylvania Cancer Center

Outcomes

Primary Outcome Measures

maximum tolerated dose

Secondary Outcome Measures

Full Information

First Posted
January 21, 2000
Last Updated
June 21, 2011
Sponsor
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00004177
Brief Title
Radiolabeled Monoclonal Antibody Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory or Recurrent Ovarian Epithelial Cancer
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 Type
Interventional

2. Study Status

Record Verification Date
June 2011
Overall Recruitment Status
Completed
Study Start Date
August 1999 (undefined)
Primary Completion Date
May 2002 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
recurrent ovarian epithelial cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Description
as prescribed by physician
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Description
1-2 weeks from treatment
Intervention Type
Radiation
Intervention Name(s)
indium In 111 monoclonal antibody MN-14
Intervention Description
intravenous infusion over 30 min; single dose
Intervention Type
Radiation
Intervention Name(s)
yttrium Y 90 monoclonal antibody MN-14
Intervention Description
intravenous infusion over 30 min; single dose
Primary Outcome Measure Information:
Title
maximum tolerated dose
Time Frame
12 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jack D. Burton, MD
Organizational Affiliation
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
Official's Role
Study Chair
Facility Information:
Facility Name
Garden State Cancer Center
City
Belleville
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
St. Joseph's Hospital and Medical Center
City
Paterson
State/Province
New Jersey
ZIP/Postal Code
07503
Country
United States
Facility Name
University of Pennsylvania Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

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

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