Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

90Y-hu3S193

111In-hu3S193

About this trial

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

Eligibility Criteria

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

Inclusion Criteria Histologically confirmed non-mucinous ovarian adenocarcinoma. Persistent or recurrent intraperitoneal cancer following platinum/taxane-based therapy for Stage 3 ovarian cancer. Patients with residual disease < 2cm will be candidates for this study. The following laboratory and clinical results within the last 2 weeks prior to study day 1: Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L; Platelet count ≥ 100 x 10^9/L; Serum bilirubin ≤ 2.0 mg/dL; Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN); Alanine aminotransferase (ALT) ≤ 2.5 x ULN; Serum creatinine ≤2.0 mg/dL; Forced expiratory volume (FEV1) ≥60% of predicted; Forced vital capacity (FVC) ≥60% of predicted; Diffusion capacity ≥55% of predicted; Left ventricular ejection fraction (LVEF) ≥50%; Karnofsky performance status ≥ 70. Before any trial-specific procedures or treatment can be performed, the patient or legally authorized guardian or representative must give witnessed written informed consent for participation in the trial. Placement of an intra-abdominal catheter at the time of surgery. Exclusion Criteria Active parenchymal disease (i.e., Stage IV International Federation of Gynecology and Obstetrics (FIGO) classification). Presence of symptomatic extra abdominal metastases. Known central nervous system (CNS) tumor involvement. Clinically significant heart disease (New York Heart Association Class III or IV). ECG demonstrating clinically significant arrhythmias or evidence of prior myocardial infarction. Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders that may limit the amount of antibody they can tolerate or render them ineligible for surgery. Chronic inflammatory bowel disease. Chemotherapy, biologic therapy, or immunotherapy within 4 weeks prior to enrollment. Pregnancy or lactation. Patients who are positive for human anti-human antibodies (HAHA) and/or who have received a murine monoclonal antibody.

Sites / Locations

Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Arm Description

Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 10 millicuries (mCi) 90Y and 5mCi 111In-hu3S193 to enable imaging after dosing.

Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 15 millicuries (mCi) 90Y and 5mCi 111In-hu3S193 to enable imaging after dosing.

Outcomes

Primary Outcome Measures

Number of Patients With Dose-limiting Toxicities (DLTs)

All adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) Scale (Version 2.0, published April 30, 1999). DLT was defined as: Any Grade 3 or greater non-hematological toxicity (except for alopecia, nausea, and vomiting, defined separately below) Any Grade alopecia Grade 4 nausea or vomiting ≥ 5 days duration. Any Grade 4 hematological toxicity (except for toxicity of ≤ 5 days duration without growth factor, platelet, or transfusion support). To be dose limiting, an adverse event must be definitely, probably, or possibly related to the administration of the investigational agent.

Secondary Outcome Measures

Clearance as Measured by the Half-life (T1/2) of the Elimination Phase

Serum samples were taken 5 min, 1 hour, and 2 hours after end of infusion, twice on study day 2, and daily on study days 3 to 7, 8, 15 and 22. Serum samples were analyzed in a gamma well counter. Elimination half-life (T1/2) was generated by fitting effective clearance to a monoexponential curve.

Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment

Blood samples were taken at baseline and on days15, 28 and 56. HAHA was measured by BIACORE.

Full Information

NCT ID

NCT00072410

First Posted

November 4, 2003

Last Updated

October 2, 2023

Sponsor

Ludwig Institute for Cancer Research

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00072410

Brief Title

Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer

Official Title

Single-Dose, Cohort Study of Increasing Doses of Yttrium-90 Conjugated to Humanized Monoclonal Antibody 3S193 (90Y-hu3S193) in Patients With Advanced Ovarian Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Completed

Study Start Date

November 2003 (Actual)

Primary Completion Date

May 2005 (Actual)

Study Completion Date

November 15, 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ludwig Institute for Cancer Research

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

Brief Summary

RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and deliver radioactive tumor-killing substances to them without harming normal cells. Giving radiolabeled monoclonal antibody directly into the abdominal cavity may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of giving radiolabeled monoclonal antibody therapy directly into the abdominal cavity in treating patients who have advanced ovarian epithelial cancer.

Detailed Description

OBJECTIVES: Primary Determine the safety and maximum tolerated dose of intraperitoneally (IP) administered yttrium-90 (90Y) radiolabeled monoclonal antibody (mAB) hu3S193 (90Y-hu3S193) in patients with advanced ovarian epithelial cancer. Secondary Determine the localization and whole body and abdominal clearance of 90Y-hu3S193 using indium-111 (111In) radiolabeled hu3S193 and gamma camera imaging. Determine the serum pharmacokinetics of hu3S193 using gamma well counting. Determine the antibody response as measured by human anti-human antibody response (HAHA). OUTLINE: This is a dose-escalation study of the yttrium-90 radiolabeled monoclonal antibody, 90Y-hu3S193. Patients received technetium (99mTc-sulfur colloid) IP and underwent abdominal imaging on day 1. Provided the distribution of the 99mTC-sulfur colloid was deemed adequate, patients then received 90Y-hu3S193 IP. 111In-hu3S193 was also administered IP over 30 minutes on day 1 to enable gamma camera imaging. Within 3-5 hours after antibody administration, patients underwent whole body imaging and single-photon emission-computed tomography (SPECT) imaging of the abdomen and pelvis. Cohorts of 3-6 patients were to receive escalating doses of 90Y-hu3S193 until the maximum tolerated dose (MTD) was determined. The MTD was defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients were to be followed every 3 months for at least 2 years and then every 6 months for up to 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, stage III ovarian epithelial cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 10 millicuries (mCi) 90Y and 5mCi 111In-hu3S193 to enable imaging after dosing.

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 15 millicuries (mCi) 90Y and 5mCi 111In-hu3S193 to enable imaging after dosing.

Intervention Type

Biological

Intervention Name(s)

90Y-hu3S193

Other Intervention Name(s)

humanized monoclonal antibody 3S193 radiolabeled with 90Y

Intervention Description

Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y.

Intervention Type

Biological

Intervention Name(s)

111In-hu3S193

Other Intervention Name(s)

humanized monoclonal antibody 3S193 radiolabeled with 111In

Intervention Description

Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193.

Primary Outcome Measure Information:

Title

Number of Patients With Dose-limiting Toxicities (DLTs)

Description

All adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) Scale (Version 2.0, published April 30, 1999). DLT was defined as: Any Grade 3 or greater non-hematological toxicity (except for alopecia, nausea, and vomiting, defined separately below) Any Grade alopecia Grade 4 nausea or vomiting ≥ 5 days duration. Any Grade 4 hematological toxicity (except for toxicity of ≤ 5 days duration without growth factor, platelet, or transfusion support). To be dose limiting, an adverse event must be definitely, probably, or possibly related to the administration of the investigational agent.

Time Frame

Up to day 56

Secondary Outcome Measure Information:

Title

Clearance as Measured by the Half-life (T1/2) of the Elimination Phase

Description

Serum samples were taken 5 min, 1 hour, and 2 hours after end of infusion, twice on study day 2, and daily on study days 3 to 7, 8, 15 and 22. Serum samples were analyzed in a gamma well counter. Elimination half-life (T1/2) was generated by fitting effective clearance to a monoexponential curve.

Time Frame

Up to 22 days

Title

Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment

Description

Blood samples were taken at baseline and on days15, 28 and 56. HAHA was measured by BIACORE.

Time Frame

Up to day 56

10. Eligibility

Sex

Female

Gender Based

Yes

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria Histologically confirmed non-mucinous ovarian adenocarcinoma. Persistent or recurrent intraperitoneal cancer following platinum/taxane-based therapy for Stage 3 ovarian cancer. Patients with residual disease < 2cm will be candidates for this study. The following laboratory and clinical results within the last 2 weeks prior to study day 1: Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L; Platelet count ≥ 100 x 10^9/L; Serum bilirubin ≤ 2.0 mg/dL; Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN); Alanine aminotransferase (ALT) ≤ 2.5 x ULN; Serum creatinine ≤2.0 mg/dL; Forced expiratory volume (FEV1) ≥60% of predicted; Forced vital capacity (FVC) ≥60% of predicted; Diffusion capacity ≥55% of predicted; Left ventricular ejection fraction (LVEF) ≥50%; Karnofsky performance status ≥ 70. Before any trial-specific procedures or treatment can be performed, the patient or legally authorized guardian or representative must give witnessed written informed consent for participation in the trial. Placement of an intra-abdominal catheter at the time of surgery. Exclusion Criteria Active parenchymal disease (i.e., Stage IV International Federation of Gynecology and Obstetrics (FIGO) classification). Presence of symptomatic extra abdominal metastases. Known central nervous system (CNS) tumor involvement. Clinically significant heart disease (New York Heart Association Class III or IV). ECG demonstrating clinically significant arrhythmias or evidence of prior myocardial infarction. Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders that may limit the amount of antibody they can tolerate or render them ineligible for surgery. Chronic inflammatory bowel disease. Chemotherapy, biologic therapy, or immunotherapy within 4 weeks prior to enrollment. Pregnancy or lactation. Patients who are positive for human anti-human antibodies (HAHA) and/or who have received a murine monoclonal antibody.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chaitanya R. Divgi, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Memorial Sloan-Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

No

Ovarian Cancer

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial