Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer

October 2, 2023 updated by: Ludwig Institute for Cancer Research

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. Histologically confirmed non-mucinous ovarian adenocarcinoma.
  2. Persistent or recurrent intraperitoneal cancer following platinum/taxane-based therapy for Stage 3 ovarian cancer.
  3. Patients with residual disease < 2cm will be candidates for this study.

  4. 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%;

  5. Karnofsky performance status ≥ 70.
  6. 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.
  7. Placement of an intra-abdominal catheter at the time of surgery.

Exclusion Criteria

  1. Active parenchymal disease (i.e., Stage IV International Federation of Gynecology and Obstetrics (FIGO) classification).
  2. Presence of symptomatic extra abdominal metastases.
  3. Known central nervous system (CNS) tumor involvement.
  4. Clinically significant heart disease (New York Heart Association Class III or IV).
  5. ECG demonstrating clinically significant arrhythmias or evidence of prior myocardial infarction.
  6. 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.
  7. Chronic inflammatory bowel disease.
  8. Chemotherapy, biologic therapy, or immunotherapy within 4 weeks prior to enrollment.
  9. Pregnancy or lactation.
  10. Patients who are positive for human anti-human antibodies (HAHA) and/or who have received a murine monoclonal antibody.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
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.
Biological: 90Y-hu3S193
Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y.
Other Names:
  • humanized monoclonal antibody 3S193 radiolabeled with 90Y
Biological: 111In-hu3S193
Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193.
Other Names:
  • humanized monoclonal antibody 3S193 radiolabeled with 111In
Experimental: Cohort 2
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.
Biological: 90Y-hu3S193
Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y.
Other Names:
  • humanized monoclonal antibody 3S193 radiolabeled with 90Y
Biological: 111In-hu3S193
Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193.
Other Names:
  • humanized monoclonal antibody 3S193 radiolabeled with 111In

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Dose-limiting Toxicities (DLTs)
Time Frame: Up to day 56

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.
Up to day 56

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clearance as Measured by the Half-life (T1/2) of the Elimination Phase
Time Frame: Up to 22 days
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.
Up to 22 days
Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment
Time Frame: Up to day 56
Blood samples were taken at baseline and on days15, 28 and 56. HAHA was measured by BIACORE.
Up to day 56

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ludwig Institute for Cancer Research

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Chaitanya R. Divgi, MD, Memorial Sloan Kettering Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2003

Primary Completion (Actual)

May 1, 2005

Study Completion (Actual)

November 15, 2006

Study Registration Dates

First Submitted

November 4, 2003

First Submitted That Met QC Criteria

November 5, 2003

First Posted (Estimated)

November 6, 2003

Study Record Updates

Last Update Posted (Actual)

October 4, 2023

Last Update Submitted That Met QC Criteria

October 2, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000339682
  • MSKCC-03069 (Other Identifier: Memorial Sloan-Kettering Cancer Center)
  • LUD2001-018 (Other Identifier: Ludwig Institute for Cancer Research)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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