Safety Study of ²¹²Pb-TCMC-Trastuzumab Radio Immunotherapy

Inclusion criteria

• At least 19 years of age.
• Life expectancy is greater than three months.
• Female subjects of child-bearing potential must have negative serum pregnancy test.
• If not surgically sterile, male and female patients of child-bearing potential must use double barrier contraception (e.g., hormonal; intrauterine device; barrier).
• Patients with HER-2 expressing tumors (e.g., ovarian, pancreatic, colon, gastric, endometrial, or breast) with measurable or non-measurable disease for which no standard therapy is available.
• HER-2 amplification by fluorescent in situ hybridization or HER-2 score of at least at least 1+ by Immunohistochemistry in more than 10% of the cells. Alternatively, HER-2 serum levels greater than 15ng/mL by ELISA.
• Disease must be predominantly intra-abdominal and should include documented peritoneal studding or positive peritoneal washings.
• Able and willing to sign an informed consent form.

Exclusion criteria

• ECOG performance status greater than 3.
• Any serious active disease or co-morbid condition that, in the opinion of the investigator, may interfere with the safety or the compliance with the study.
• Poor bone marrow reserve as defined by absolute neutrophil count less than 1.5 x 10³/cmm or platelets less than 100 x 10³/cmm within two weeks prior to initiation of treatment.
• Liver only metastases.
• Poor organ function as defined by one of the following:

• Total bilirubin greater than 1.5 upper limits of normal (ULN)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) greater than 2.5 ULN or greater than 5 ULN in case of documented liver metastasis
• Serum creatinine greater than ULN, except if calculated creatinine clearance greater than 60 mL/min
• Urine Protein/Creatinine Ratio greater than 1 on morning spot urinalysis or proteinuria greater than 500 mg/24 h
• Breast-feeding woman.
• No resolution of all specific toxicities (excluding alopecia) related to any prior anticancer therapy to Grade 2 according to the National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) v.4.03 or nausea and vomiting to Grade 3 and uncontrolled with anti-emetics.
• Wash out period of less than three weeks from previous anti-tumor therapy or any investigational treatment (and less than six weeks in case of prior nitroso-urea and or mitomycin C treatment) of scheduled date of administration.
• Wash out period of less than one week from last palliative dose of radiotherapy.
• Any other severe underlying medical conditions that could impair the ability to participate in the study or the interpretation of its results related to the investigational product such as:

• Patients with abnormal cardiac function defined by a left ventricular ejection fraction (LVEF) less than 50% by echocardiogram (ECHO) or multi gated acquisition (MUGA) scan
• Patients with previous history of acute cardiac failure
• Clinical symptoms of bowel obstruction, evidence of rectosigmoid bowel involvement on exam, or transmural bowel wall involvement on computed tomography (CT) or magnetic resonance imaging (MRI).
• Prior whole abdomen radiation therapy exceeding 4Gy, intraperitoneal radionuclide therapy, bone marrow transplant, or stem cell transplant.
• History of Human Immunodeficiency Virus (HIV) antibody by enzyme-linked immunosorbent assay (ELISA) or negative by Western blot (if ELISA is positive) or hepatitis B surface antigen (HBsAg) because of the potential for added toxicity from the radiolabeled antibody among patients infected with these viruses.
• Detectable human anti-human antibody (HAHA) if there is any history of monoclonal antibody exposure.
• Iodine allergy if the patient is unwilling to accept radiation to the thyroid from uptake of radionuclide without blocking.
• Allergy to furosemide if the patient is unwilling to accept radiation risk without these agents and alternative is not feasible.
• History of cumulative anthracycline therapy exceeding 200 mg/m² for doxorubicin or comparable low dose of other anthracyclines.