Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer

NCT ID: NCT00072410

Last Updated: 2023-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-11-30
• Study Completion Date: 2006-11-15

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.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

90Y-hu3S193

Intervention Type: BIOLOGICAL

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

111In-hu3S193

Intervention Type: BIOLOGICAL

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

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.

Group Type: EXPERIMENTAL

90Y-hu3S193

Intervention Type: BIOLOGICAL

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

111In-hu3S193

Intervention Type: BIOLOGICAL

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

Interventions

90Y-hu3S193

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

Intervention Type: BIOLOGICAL

111In-hu3S193

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

Intervention Type: BIOLOGICAL

Other Intervention Names

humanized monoclonal antibody 3S193 radiolabeled with 90Y; humanized monoclonal antibody 3S193 radiolabeled with 111In

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Ludwig Institute for Cancer Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chaitanya R. Divgi, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

MSKCC-03069

Identifier Type: OTHER

Identifier Source: secondary_id

LUD2001-018

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000339682

Identifier Type: -

Identifier Source: org_study_id