Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer

• ClinicalTrials.gov Identifier: NCT00072410
• Recruitment Status: Completed
• First Posted: November 6, 2003
• Results First Posted: December 21, 2021
• Last Update Posted: December 21, 2021
• Sponsor: Ludwig Institute for Cancer Research
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Ludwig Institute for Cancer Research

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.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer	Biological: 90Y-hu3S193; Biological: 111In-hu3S193	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 2003
• Actual Primary Completion Date: May 2005
• Actual Study Completion Date: November 15, 2006

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: humanized monoclonal antibody 3S193 radiolabeled with 111In

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, New York

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

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

More Information

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT00072410
• Other Study ID Numbers: CDR0000339682; MSKCC-03069 ( Other Identifier: Memorial Sloan-Kettering Cancer Center ); LUD2001-018 ( Other Identifier: Ludwig Institute for Cancer Research )
• First Posted: November 6, 2003
• Results First Posted: December 21, 2021
• Last Update Posted: December 21, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• 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:

recurrent ovarian epithelial cancer; stage III ovarian epithelial cancer

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents