Phase I Trial of Intraperitoneal ²¹²Pb-TCMC-Trastuzumab for HER-2 Expressing Malignancy
1. At least 19 years of age.
2. Life expectancy is greater than three months.
3. Female subjects of child-bearing potential must have negative serum pregnancy test.
4. If not surgically sterile, male and female patients of child-bearing potential must
use double barrier contraception (e.g., hormonal; intrauterine device; barrier).
5. 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.
6. 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 is acceptable for
gastric, 30% for other diseases. Alternatively, HER-2 serum levels greater than
15ng/mL by ELISA.
7. Disease must be predominantly intra-abdominal and should include documented
peritoneal studding or positive peritoneal washings.
8. Able and willing to sign an informed consent form.
1. Eastern Cooperative Oncology Group (ECOG) performance status greater than 3.
2. 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.
3. Poor bone marrow reserve as defined by absolute neutrophil count less than 1.5 x 10³
per millimeter cube (/cmm) or platelets less than 100 x 10³/cmm within two weeks
prior to initiation of treatment.
4. Liver only metastases.
5. 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
6. Breast-feeding woman.
7. 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.
8. 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.
9. Wash out period of less than one week from last palliative dose of radiotherapy.
10. 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
11. 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).
12. Prior whole abdomen radiation therapy exceeding 4Gy, intraperitoneal radionuclide
therapy, bone marrow transplant, or stem cell transplant.
13. 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.
14. Detectable human anti-human antibody (HAHA) if there is any history of monoclonal
15. Iodine allergy if the patient is unwilling to accept radiation to the thyroid from
uptake of radionuclide without blocking.
16. Allergy to furosemide or spironolactone if the patient is unwilling to accept
radiation risk without these agents and alternatives are not feasible.
17. History of cumulative anthracycline therapy exceeding 200 mg/m² for doxorubicin or
comparable low dose of other anthracyclines.