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)
• Enrollment: 1
• Location: 1
• Arms: 2
• Actual Duration (Months): 24.3
• Patients Per Site Per Month: 0

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 Disease	Intervention/Treatment	Phase
Ovarian Cancer	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

Arm	Intervention/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

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

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: ovarian epithelial cancer
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Antibodies; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Intraperitoneal (IP) Infusion of 111In-hu3S193	Intravenous Infusion of 111In-hu3S193
Arm/Group Description	Hu3S193 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
STARTED	1	0
COMPLETED	1	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Intraperitoneal (IP) Infusion of 111In-hu3S193	Intravenous Infusion of 111In-hu3S193	Total
Arm/Group Description	Hu3S193 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 Participants	1	0	1
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

Title	Number of Subjects With Grade 3 Adverse Events
Description	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.
Time Frame	up to 30 days

Outcome Measure Data

Analysis Population Description

The 1 patient who entered the study.

Arm/Group Title	Intraperitoneal (IP) Infusion of 111In-hu3S193	Intravenous Infusion of 111In-hu3S193
Arm/Group Description	Hu3S193 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 Participants	1	0
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	up 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 Title	Intraperitoneal (IP) Infusion of 111In-hu3S193		Intravenous Infusion of 111In-hu3S193
Arm/Group Description	Hu3S193 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-hu3S193		Intravenous Infusion of 111In-hu3S193
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)
Serious Adverse Events
	Intraperitoneal (IP) Infusion of 111In-hu3S193		Intravenous Infusion of 111In-hu3S193
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Intraperitoneal (IP) Infusion of 111In-hu3S193		Intravenous Infusion of 111In-hu3S193
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (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.