Monoclonal Antibody Therapy in Treating Patients Scheduled for Surgery to Remove Ovarian Cancer

Sponsor
Ludwig Institute for Cancer Research (Other)
Overall Status
Terminated
CT.gov ID
NCT00006099
Collaborator
National Cancer Institute (NCI) (NIH)
1
Enrollment
1
Location
2
Arms
24.3
Actual Duration (Months)
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Giving monoclonal antibodies in different ways may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have ovarian cancer.

Condition or DiseaseIntervention/TreatmentPhase
  • Biological: Monoclonal antibody hu3S193
Phase 1

Detailed Description

OBJECTIVES: The primary objective iss to determine the safety of indium (111In) monoclonal antibody (mAb) hu3S193 (111In-hu3S193) given intraperitoneally or intravenously in patients with ovarian carcinoma.

Secondary objectives include comparing the localization of 111In-hu3S193 in ovarian cancer tissue after intraperitoneal vs intravenous injection and the biodistribution and pharmacokinetics of this drug when administered intraperitoneally vs intravenously in these patients as well as the formation of human anti-human antibodies (HAHA) in these patients.

OUTLINE: Patients are assigned to 1 of 2 treatment arms on a first come sequential basis. Arm I: Patients receive indium (In 111) monoclonal antibody hu3S193 (111In-hu3S193) intraperitoneally over 30 minutes. Arm II: Patients received 111In-hu3S193 intravenously (IV) over 30 minutes. Patients were to undergo surgical debulking 3-7 days following In 111In-hu3S193 administration, and biopsy samples obtained to assess radioactive uptake. Immunohistochemistry was also to be performed. Blood samples were to be obtained to assess serum radioactivity. Whole body imaging was tp be performed 3 hours after infusion of radiolabeled monoclonal antibody, on the day of surgery, and at one time point in between. Patients were followed for 30 days.

PROJECTED ACCRUAL: A total of 10 patients (5 per arm) were to be accrued for this study.

Study Design

Study Type:
Interventional
Actual Enrollment :
1 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
Pilot Trial of Humanized 3S193 Monoclonal Antibody (hu3S193) in Presurgical Patients With Ovarian Cancer
Actual Study Start Date :
Aug 2, 2000
Actual Primary Completion Date :
Feb 26, 2002
Actual Study Completion Date :
Aug 12, 2002

Arms and Interventions

ArmIntervention/Treatment
Experimental: Intraperitoneal (IP) Infusion of 111In-hu3S193

Hu3S193 was administered intraperitoneally at a dose of 5 mg radiolabeled with 5 millicurie (mCi) of 111In. Patients received 10 mCi 99mTc-sulphur colloid IP administered in 500 ml of normal saline to assure the absence of any loculation or heterogeneous distribution of radioactivity in the peritoneal cavity. A paracentesis catheter was inserted and the hu3S193 was diluted in 100 mL of 5% human serum albumin and administered as a continuous intraperitoneal infusion over 30 minutes. This was followed immediately by 900 mL of normal saline.

Biological: Monoclonal antibody hu3S193
Hu3S193 was to be administered intraperitoneally or intravenously at a dose of 5mg. Doses of hu3S193 were radiolabeled with 5 mCi of 111In.

Experimental: Intravenous Infusion of 111In-hu3S193

Hu3S193 was to be administered intravenously at a dose of 5 mg radiolabeled with 5 millicurie (mCi) of 111In, diluted in 100 mL of 5% human serum albumin and administered over a 30 minute period.

Biological: Monoclonal antibody hu3S193
Hu3S193 was to be administered intraperitoneally or intravenously at a dose of 5mg. Doses of hu3S193 were radiolabeled with 5 mCi of 111In.

Outcome Measures

Primary Outcome Measures

  1. Number of Subjects With Grade 3 Adverse Events [up to 30 days]

    All toxicities were to be graded according to the Common Toxicity Criteria (CTC) Scale, version 2.0, March 1998.The study was to be terminated upon the occurrence of an adverse event of Grade 3 or greater severity that is considered definitely related to hu3S193.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No

Inclusion Criteria

Cytologic or pathologic diagnosis consistent with ovarian carcinoma. Scheduled to undergo surgical evaluation. Karnofsky performance status of > 60%.

Adequate organ function as defined by:
  • Absolute neutrophil count (ANC) > 1.5 x 10^9/L

  • Platelet count > 100 x 10^9/L

  • Bilirubin < 2.0 mg/dL

  • Aspartate aminotransferase (AST) and Alanine transaminase (ALT) < 2.5 X upper limit of normal

  • Serum creatinine < 2.0 mg/dL

  • Forced expiratory volume at one second (FEV1) and forced vital capacity (FVC)> 70% of predicted

  • Left Ventricular Ejection Fraction >50%

Recovered from the toxicity of any prior therapy. No evidence of active infection which requires antibiotic therapy. > 18 years of age. Able to sign written informed consent.

Exclusion Criteria

Any significant intercurrent medical problems which may limit the amount of antibody they can tolerate, or render them ineligible for surgery.

Clinically significant cardiac disease (New York Heart Association Class III/IV, or abnormalities on ECG that are considered by the investigator to place the patient at increased risk), severe debilitating pulmonary disease, active infections or coagulation disorders.

Survival expectancy less than 12 weeks. History of autoimmune hepatitis or history of autoimmune disease. Chemotherapy, radiotherapy, or immunotherapy within four weeks prior to receiving hu3S193.

Psychiatric, addictive or other disorders that compromise the ability to give informed consent.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Memorial Sloan-Kettering Cancer CenterNew YorkNew YorkUnited States10021

Sponsors and Collaborators

  • Ludwig Institute for Cancer Research
  • National Cancer Institute (NCI)

Investigators

  • Study Chair: Chaitanya R. Divgi, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:
NCT00006099
Other Study ID Numbers:
  • CDR0000068107
  • MSKCC-00047
  • NCI-G00-1828
  • LUD1998-013
First Posted:
Dec 23, 2003
Last Update Posted:
Aug 12, 2021
Last Verified:
Jul 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Ludwig Institute for Cancer Research
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group TitleIntraperitoneal (IP) Infusion of 111In-hu3S193Intravenous Infusion of 111In-hu3S193
Arm/Group DescriptionHu3S193 was administered intraperitoneally (IP) at a dose of 5 mg radiolabeled with 5 millicurie (mCi) of 111In. Patients received 10 mCi 99mTc-sulphur colloid IP administered in 500 ml of normal saline to assure the absence of any loculation or heterogeneous distribution of radioactivity in the peritoneal cavity. A paracentesis catheter was inserted and the hu3S193 was diluted in 100 mL of 5% human serum albumin and administered as a continuous intraperitoneal infusion over 30 minutes. This was followed immediately by 900 mL of normal saline.Hu3S193 was to be administered intravenously at a dose of 5 mg radiolabeled with 5 millicurie (mCi) of 111In, diluted in 100 mL of 5% human serum albumin and administered over a 30 minute period.
Period Title: Overall Study
STARTED10
COMPLETED10
NOT COMPLETED00

Baseline Characteristics

Arm/Group TitleIntraperitoneal (IP) Infusion of 111In-hu3S193Intravenous Infusion of 111In-hu3S193Total
Arm/Group DescriptionHu3S193 was administered intraperitoneally at a dose of 5 mg radiolabeled with 5 mCi of 111In. Patients received 10 mCi 99mTc-sulphur colloid IP administered in 500 ml of normal saline to assure the absence of any loculation or heterogeneous distribution of radioactivity in the peritoneal cavity. A paracentesis catheter was inserted and the hu3S193 was diluted in 100 mL of 5% human serum albumin and administered as a continuous intraperitoneal infusion over 30 minutes. This was followed immediately by 900 mL of normal saline.Hu3S193 was to be administered intravenously at a dose of 5 mg radiolabeled with 5 mCi of 111In, diluted in 100 mL of 5% human serum albumin and administered over a 30 minute period.Total of all reporting groups
Overall Participants101
Age (Count of Participants)
<=18 years
0
0%
0
NaN
Between 18 and 65 years
1
100%
1
Infinity
>=65 years
0
0%
0
NaN
Sex: Female, Male (Count of Participants)
Female
1
100%
1
Infinity
Male
0
0%
0
NaN
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
NaN
Asian
0
0%
0
NaN
Native Hawaiian or Other Pacific Islander
0
0%
0
NaN
Black or African American
0
0%
0
NaN
White
1
100%
1
Infinity
More than one race
0
0%
0
NaN
Unknown or Not Reported
0
0%
0
NaN
Region of Enrollment (participants) [Number]
United States
1
100%
1
Infinity

Outcome Measures

1. Primary Outcome
TitleNumber of Subjects With Grade 3 Adverse Events
DescriptionAll toxicities were to be graded according to the Common Toxicity Criteria (CTC) Scale, version 2.0, March 1998.The study was to be terminated upon the occurrence of an adverse event of Grade 3 or greater severity that is considered definitely related to hu3S193.
Time Frameup to 30 days

Outcome Measure Data

Analysis Population Description
The 1 patient who entered the study.
Arm/Group TitleIntraperitoneal (IP) Infusion of 111In-hu3S193Intravenous Infusion of 111In-hu3S193
Arm/Group DescriptionHu3S193 was administered intraperitoneally at a dose of 5 mg radiolabeled with 5 mCi of 111In. Patients received 10 mCi 99mTc-sulphur colloid IP administered in 500 ml of normal saline to assure the absence of any loculation or heterogeneous distribution of radioactivity in the peritoneal cavity. A paracentesis catheter was inserted and the hu3S193 was diluted in 100 mL of 5% human serum albumin and administered as a continuous intraperitoneal infusion over 30 minutes. This was followed immediately by 900 mL of normal saline.Hu3S193 was to be administered intravenously at a dose of 5 mg radiolabeled with 5 mCi of 111In, diluted in 100 mL of 5% human serum albumin and administered over a 30 minute period.
Measure Participants10
Count of Participants [Participants]
0
0%

Adverse Events

Time Frameup to 30 days
Adverse Event Reporting Description All adverse events were to be recorded on the patient's case report form. All toxicities were to be graded according to the Common Toxicity Criteria (CTC) Scale, version 2.0, March 1998.
Arm/Group TitleIntraperitoneal (IP) Infusion of 111In-hu3S193Intravenous Infusion of 111In-hu3S193
Arm/Group DescriptionHu3S193 was administered intraperitoneally at a dose of 5 mg radiolabeled with 5 mCi of 111In. Patients received 10 mCi 99mTc-sulphur colloid IP administered in 500 ml of normal saline to assure the absence of any loculation or heterogeneous distribution of radioactivity in the peritoneal cavity. A paracentesis catheter was inserted and the hu3S193 was diluted in 100 mL of 5% human serum albumin and administered as a continuous intraperitoneal infusion over 30 minutes. This was followed immediately by 900 mL of normal saline.Hu3S193 was to be administered intravenously at a dose of 5 mg radiolabeled with 5 mCi of 111In, diluted in 100 mL of 5% human serum albumin and administered over a 30 minute period.
All Cause Mortality
Intraperitoneal (IP) Infusion of 111In-hu3S193Intravenous Infusion of 111In-hu3S193
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/1 (0%) 0/0 (NaN)
Serious Adverse Events
Intraperitoneal (IP) Infusion of 111In-hu3S193Intravenous Infusion of 111In-hu3S193
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/1 (0%) 0/0 (NaN)
Other (Not Including Serious) Adverse Events
Intraperitoneal (IP) Infusion of 111In-hu3S193Intravenous Infusion of 111In-hu3S193
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/1 (0%) 0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/TitleMary Macri, Senior Director, Clinical Trials Management
OrganizationLudwig Institute for Cancer Research
Phone12124501546
Emailmmacri@lcr.org
Responsible Party:
Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:
NCT00006099
Other Study ID Numbers:
  • CDR0000068107
  • MSKCC-00047
  • NCI-G00-1828
  • LUD1998-013
First Posted:
Dec 23, 2003
Last Update Posted:
Aug 12, 2021
Last Verified:
Jul 1, 2021