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Radiolabeled Monoclonal Antibody, Paclitaxel, and Interferon Alfa in Treating Patients With Recurrent Ovarian Cancer

Primary Purpose

Ovarian Cancer, Primary Peritoneal Cavity Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
recombinant interferon alfa
chemotherapy
paclitaxel
topotecan hydrochloride
lutetium Lu 177 monoclonal antibody CC49
yttrium Y 90 monoclonal antibody CC49
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

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

Eligibility Criteria

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

DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the ovary or papillary serous carcinoma of extraovarian origin Recurrent or persistent following standard surgery and 1 or 2 chemotherapy regimens (with or without paclitaxel), i.e.: persistent disease or progression after chemotherapy with nodules less than the equivalent of 5 x 5 x 5 cm Recurrent carcinoma (after primary or secondary chemotherapy) detected clinically either by exam or rising CA 125 and with radiographic evidence of disease no greater than the equivalent of 5 x 5 x 5 cm nodules Residual disease less than 5 x 5 x 5 cm following reassessment laparotomy Microscopic residual disease on reassessment laparotomy after chemotherapy Tumor TAG-72 positive by immunoperoxidase staining of original or current tumor blocks At least 85% free flow of fluid in peritoneal cavity demonstrated by technetium-99m scan or other imaging within 2 weeks prior to treatment No evidence of disease outside the peritoneal cavity other than retroperitoneal lymphadenopathy No massive ascites PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 WBC at least 3,500/mm3 Platelet count at least 125,000/mm3 Hemoglobin greater than 9 g/dL No nucleated RBC or significant teardrop RBC morphology Bilirubin less than 1.5 mg/dL AST/ALT less than 4 times normal Creatinine less than 2.0 mg/dL HIV negative Hepatitis B surface antigen negative No hypersensitivity to paclitaxel, polyoxethylated castor oil, or topotecan No other malignancy in past 5 years except basal cell skin carcinoma Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: At least 3 weeks since prior biologic therapy and recovered No prior monoclonal antibody therapy No concurrent immunotherapy No prior bone marrow or stem cell transplantation At least 3 weeks since prior chemotherapy (6 weeks since nitrosoureas or mitomycin) and recovered No concurrent chemotherapy At least 3 weeks since prior radiotherapy and recovered No prior radiotherapy to the abdominal cavity No concurrent radiotherapy At least 3 weeks since prior major surgery and recovered No prior intraperitoneal therapy

Sites / Locations

  • University of Alabama Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

Patients receive interferon alfa subcutaneously on days 1, 3, 5, and 7; paclitaxel intraperitoneally (IP) on day 4 or topotecan IP on day 6; and 177Lu-CC49 IP on day 6. Treatment continues every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-5 patients receive escalating doses of paclitaxel and decreasing doses of 177Lu-CC49 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 5 patients experience dose limiting toxicity. Once the MTD of paclitaxel is determined, the dose of 177Lu-CC49 is escalated. Once the MTD of 177Lu-CC49 is determined, 90Y-CC49 is substituted. The MTD of 90Y-CC49 is then determined when administered with paclitaxel. Topotecan is then substituted for paclitaxel (administered with the MTD of 177Lu-CC49 and interferon alfa only) and escalated until the MTD is determined.

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
February 4, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00002734
Brief Title
Radiolabeled Monoclonal Antibody, Paclitaxel, and Interferon Alfa in Treating Patients With Recurrent Ovarian Cancer
Official Title
PHASE I STUDY OF INTERFERON ENHANCED INTRAPERITONEAL RADIOIMMUNO-CHEMOTHERAPY FOR OVARIAN CANCER
Study Type
Interventional

2. Study Status

Record Verification Date
February 2001
Overall Recruitment Status
Completed
Study Start Date
March 1996 (undefined)
Primary Completion Date
April 2001 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
Phase I trial to study the effectiveness of radiolabeled monoclonal antibody, paclitaxel, and interferon alfa in treating patients who have ovarian cancer. Radiolabeled monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interferon may interfere with the growth of cancer cells. Combining monoclonal antibody, chemotherapy, and interferon alfa may kill more tumor cells.
Detailed Description
OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of intraperitoneal paclitaxel and topotecan when administered as a radiosensitizer prior to intraperitoneal lutetium Lu 177 monoclonal antibody CC49 (177Lu-CC49) following subcutaneous interferon alfa-2b (IFN-A) in patients with persistent or recurrent ovarian cancer. II. Determine the toxicity associated with intraperitoneal paclitaxel and topotecan in these patients. III. Examine the conjugate stability, pharmacokinetics, and biodistribution of 177Lu-CC49 given 48 hours after intraperitoneal paclitaxel. IV. Determine the effects of IFN-A and intraperitoneal paclitaxel on 177Lu-CC49 tumor localization and dosimetry estimates compared to a prior trial with 177Lu-CC49 alone. V. Determine the MTD of yttrium Y 90 monoclonal antibody CC49 (90Y-CC49) when administered with IFN-A and the dose of paclitaxel used at the MTD level of IFN-A, paclitaxel, and 177Lu-CC49. VI. Monitor any antitumor effects of this treatment in these patients. OUTLINE: This is a dose escalation study of paclitaxel, topotecan, lutetium LU 177 monoclonal antibody CC-49 (177Lu-CC49), and yttrium Y 90 monoclonal antibody CC49 (90Y-CC49). Patients receive interferon alfa subcutaneously on days 1, 3, 5, and 7; paclitaxel intraperitoneally (IP) on day 4 or topotecan IP on day 6; and 177Lu-CC49 IP on day 6. Treatment continues every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-5 patients receive escalating doses of paclitaxel and decreasing doses of 177Lu-CC49 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 5 patients experience dose limiting toxicity. Once the MTD of paclitaxel is determined, the dose of 177Lu-CC49 is escalated. Once the MTD of 177Lu-CC49 is determined, 90Y-CC49 is substituted. The MTD of 90Y-CC49 is then determined when administered with paclitaxel. Topotecan is then substituted for paclitaxel (administered with the MTD of 177Lu-CC49 and interferon alfa only) and escalated until the MTD is determined. Patients are followed at 6 weeks and then every 3 months for 1 year.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients receive interferon alfa subcutaneously on days 1, 3, 5, and 7; paclitaxel intraperitoneally (IP) on day 4 or topotecan IP on day 6; and 177Lu-CC49 IP on day 6. Treatment continues every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-5 patients receive escalating doses of paclitaxel and decreasing doses of 177Lu-CC49 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 5 patients experience dose limiting toxicity. Once the MTD of paclitaxel is determined, the dose of 177Lu-CC49 is escalated. Once the MTD of 177Lu-CC49 is determined, 90Y-CC49 is substituted. The MTD of 90Y-CC49 is then determined when administered with paclitaxel. Topotecan is then substituted for paclitaxel (administered with the MTD of 177Lu-CC49 and interferon alfa only) and escalated until the MTD is determined.
Intervention Type
Biological
Intervention Name(s)
recombinant interferon alfa
Intervention Type
Drug
Intervention Name(s)
chemotherapy
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Type
Drug
Intervention Name(s)
topotecan hydrochloride
Intervention Type
Radiation
Intervention Name(s)
lutetium Lu 177 monoclonal antibody CC49
Intervention Type
Radiation
Intervention Name(s)
yttrium Y 90 monoclonal antibody CC49

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the ovary or papillary serous carcinoma of extraovarian origin Recurrent or persistent following standard surgery and 1 or 2 chemotherapy regimens (with or without paclitaxel), i.e.: persistent disease or progression after chemotherapy with nodules less than the equivalent of 5 x 5 x 5 cm Recurrent carcinoma (after primary or secondary chemotherapy) detected clinically either by exam or rising CA 125 and with radiographic evidence of disease no greater than the equivalent of 5 x 5 x 5 cm nodules Residual disease less than 5 x 5 x 5 cm following reassessment laparotomy Microscopic residual disease on reassessment laparotomy after chemotherapy Tumor TAG-72 positive by immunoperoxidase staining of original or current tumor blocks At least 85% free flow of fluid in peritoneal cavity demonstrated by technetium-99m scan or other imaging within 2 weeks prior to treatment No evidence of disease outside the peritoneal cavity other than retroperitoneal lymphadenopathy No massive ascites PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 WBC at least 3,500/mm3 Platelet count at least 125,000/mm3 Hemoglobin greater than 9 g/dL No nucleated RBC or significant teardrop RBC morphology Bilirubin less than 1.5 mg/dL AST/ALT less than 4 times normal Creatinine less than 2.0 mg/dL HIV negative Hepatitis B surface antigen negative No hypersensitivity to paclitaxel, polyoxethylated castor oil, or topotecan No other malignancy in past 5 years except basal cell skin carcinoma Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: At least 3 weeks since prior biologic therapy and recovered No prior monoclonal antibody therapy No concurrent immunotherapy No prior bone marrow or stem cell transplantation At least 3 weeks since prior chemotherapy (6 weeks since nitrosoureas or mitomycin) and recovered No concurrent chemotherapy At least 3 weeks since prior radiotherapy and recovered No prior radiotherapy to the abdominal cavity No concurrent radiotherapy At least 3 weeks since prior major surgery and recovered No prior intraperitoneal therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ruby F. Meredith, MD, PhD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States

12. IPD Sharing Statement

Citations:
Citation
Meredith R, Alvarez R, Khazaeli MB, et al.: Intraperitoneal radioimmunotherapy for refractory epithelial ovarian cancer with Lu-CC49. Minerva Biotechnologica 10: 100-107, 1998.
Results Reference
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Radiolabeled Monoclonal Antibody, Paclitaxel, and Interferon Alfa in Treating Patients With Recurrent Ovarian Cancer

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