Monoclonal antibodies can transport and deliver radioactive elements capable of releasing sufficient amounts of energy to destroy tumor cells. In this clinical trial, we will study alpha particle radio immunotherapy using lead-212 (²¹²Pb), an isotope with a short path length targeted to malignant cells by the trastuzumab antibody, as a potential treatment for metastatic diseases. This Phase I trial is designed to determine the toxicity profile of ²¹²Pb-TCMC-Trastuzumab, its dose-limiting toxicities, and its anti-tumor effects in patients with HER-2 positive intraperitoneal cancers.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
The starting dose level will be 200 μCi/m² of ²¹²Pb-TCMC-Trastuzumab. Three to six patients will be treated at each dose level, and dose escalation will proceed if no more than 1 out of 6 patients in a cohort experiences dose limiting toxicity. Six patients will be treated at the maximum tolerated dose.
4 mg/kg.
University Of Alabama at Birmingham
Birmingham, Alabama, United States
UCSD Moores Cancer Center
San Diego, California, United States
Safety and tolerability: To measure the number of participants who experience adverse events after intraperitoneal (IP) administration of ²¹²Pb-TCMC-Trastuzumab.
Adverse events considered dose limiting toxicity: * Grade 3 elevations of ALP, bilirubin, ALT, or AST lasting ≥7 days * Grade 3 elevations of serum creatinine within 6 weeks of treatment * Grade 2 elevations of serum creatinine lasting ≥7 days that occur after 6 weeks * Grade 3 proteinuria * Any other Grade 3 or 4 non-hematologic toxicity * Grade 4 neutropenia lasting ≥7 days or febrile neutropenia of any duration * Grade 3 thrombocytopenia that fails to recover to ≤ Grade 2 at 6 weeks * Grade 4 thrombocytopenia lasting ≥7 days or thrombocytopenia accompanied by bleeding
Time frame: Assessed periodically during study treatment follow-up, up to five years.
Immunogenicity: To characterize the human immune response against ²¹²Pb-TCMC-Trastuzumab given via IP infusion.
Time frame: Assessed at six weeks visit
Anti-tumor effects: To monitor for anti-tumor effects as assessed by physical examination, radiographic imaging, and tumor marker studies.
Time frame: Assessed after six and twelve weeks, and then at twelve-week intervals until progression.
Pharmacokinetics: To determine the plasma pharmacokinetics and assess the extent of exit of radioactivity from the peritoneal cavity by γ-camera imaging.
Time frame: Up to 3 days post-injection
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