Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer
- Conditions
- Ovarian Cancer
- Interventions
- Biological: 90Y-hu3S193Biological: 111In-hu3S193
- Registration Number
- NCT00072410
- Lead Sponsor
- Ludwig Institute for Cancer Research
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 7
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 111In-hu3S193 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. Cohort 2 90Y-hu3S193 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. Cohort 2 111In-hu3S193 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. Cohort 1 90Y-hu3S193 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.
- Primary Outcome Measures
Name Time Method Number of Patients With Dose-limiting Toxicities (DLTs) 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
Name Time Method Clearance as Measured by the Half-life (T1/2) of the Elimination Phase 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.
Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment Up to day 56 Blood samples were taken at baseline and on days15, 28 and 56. HAHA was measured by BIACORE.
Trial Locations
- Locations (1)
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States