Biodistribution Study of CMD-193 in Patients With Advanced Tumours Expressing the Lewis-Y Antigen
Condition: Neoplasms
Intervention: 111-Indium-CMD-193; CMD-193
Intervention description: 111-In-CMD-193 (3-7 mCi) was administered as an IV infusion over 60 (± 5) minutes.; CMD-193 was administered as an IV infusion over 60 (± 5) minutes.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This was a Phase 1 dose-escalation study of CMD-193, a humanized monoclonal antibody linked
      to the toxin calicheamicin, in subjects with advanced tumors expressing the Lewis-Y antigen.
      The primary study objective was to determine the biodistribution and pharmacokinetics (PK) of
      111-In-CMD-193 (i.e., CMD-193 tagged with a small amount of radioactive Indium [111-In]),
      with secondary objectives of determining changes in tumor metabolism and describing the
      antitumor responses to CMD-193.
    

Eligibility criteria:

        Inclusion criteria:

          1. Signed and dated Institutional Review Board (IRB)-approved informed consent before any
             protocol-specific screening procedures were performed.

          2. Histologically confirmed malignant solid tumor that had progressed following standard
             therapy, or for which no standard effective treatment was available.

          3. Tumor expression of Lewis-Y antigen (≥20% tumor cells positive for Lewis-Y by
             immunohistochemistry assay).

          4. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors
             (RECIST), including the presence of at least one measurable lesion at least 2 cm in
             size suitable for 18F-FDG PET imaging.

          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          6. Life expectancy ≥ 18 weeks.

          7. Age ≥18 years.

          8. Recovery to National Cancer Institute (NCI) Common Terminology Criteria for Adverse
             Events (CTCAE) ≤ Grade 1 toxicity from any significant effects of prior surgery,
             radiation therapy, and cancer therapy (except alopecia).

          9. Renal test: serum creatinine ≤ 1.5 x upper limit of normal (ULN).

         10. Hepatic tests: alanine aminotransferase (ALT) levels ≤2.5 x ULN and total bilirubin
             ≤1.5 x ULN.

         11. Pancreatic tests: amylase ≤1.5 x ULN and lipase ≤ 1.5 x ULN.

         12. Bone marrow tests: absolute neutrophil count (ANC) of ≥1500 mm^3 (≥1.5 x 10^9/L) and
             platelet count of ≥ 150,000/mm^3 (≥150 x 10^9/L).

         13. For women of childbearing potential, a negative serum pregnancy test result no longer
             than 48 hours before the first dose of CMD-193. A woman of childbearing potential was
             one who was biologically capable of becoming pregnant. This included women who were
             using contraceptives or whose sexual partners were either sterile or using
             contraceptives.

         14. All subjects who were not surgically sterile or postmenopausal must have agreed and
             committed to the use of a reliable method of birth control for the duration of the
             study and for 28 days after the last dose of CMD-193.

         15. Willingness of female subjects to refrain from breastfeeding infants during the study
             or within 28 days after the last dose of CMD-193.

        Exclusion Criteria

          1. Chemotherapy, radiation therapy, other cancer therapy, or investigational agents
             within 21 days of the first dose of CMD-193 (42 days if the previous chemotherapy
             included nitrosoureas or mitomycin C).

          2. Symptomatic or clinically active central nervous system (CNS) metastases. Subjects who
             had prior treatment with radiotherapy or surgical resection for CNS metastases were
             permitted if CNS metastases had remained stable and not required any treatment for at
             least 3 months prior to the first dose of CMD-193.

          3. Significant prior allergic reaction to recombinant human or murine proteins.

          4. History of cirrhosis, current or chronic hepatitis B or C infections, or other
             significant active liver disease.

          5. Unstable or serious concurrent medical conditions. Examples included, but were not
             limited to, bleeding gastric ulcers, gastrointestinal bleeding, hepatitis, significant
             disorders of the immune system (eg, systemic lupus erythematosus), pancreatitis,
             congestive heart failure, serious active infections (e.g. requiring antibiotics or
             antiviral agents), unstable angina, recent myocardial infarction (within 6 months of
             screening), ongoing maintenance therapy for life-threatening ventricular arrhythmia,
             or uncontrolled major seizure disorder.

          6. Other malignancy within 3 years prior to entry into the study, except for treated
             non-melanoma skin cancer and cervical carcinoma in situ.

          7. Any other condition that, in the Investigator's judgment, would have substantially
             increased the risk associated with the subject's participation in this study.