Phase I Trial of huA33 Plus Chemotherapy in Patients With Metastatic Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Oxaliplatin; 5-Fluorouracil; Leucovorin; huA33
Intervention description: Oxaliplatin was administered at 85 mg/m2 on day 2 of every 2 week regimen.; The dose of 5-FU was 400 mg/m2 IV bolus followed by continuous IV infusion at 600 mg/m2 over 22 hours on day 2 and day 3 of every 2 week regimen.; Leucovorin was administered at a dose of 200mg/m2 on day 2 and day 3 of every 2 week regimen.; huA33 was administered intravenously over a period of 30 minutes once a week at a dose of 10 mg/m2.
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Colorectal Cancer; huA33; antibody; chemotherapy

Summary:

      Although treatment for metastatic colorectal cancer has improved significantly over the
      recent years, it still remains a significant health problem representing the leading cancer
      by incidence in the United States of America. In the search for new therapies, monoclonal
      antibodies have been developed to specifically target human colon cancer cells. huA33 is an
      antibody that reacts with the A33 antigen which is produced by colorectal cancers. Prior
      studies have shown that administration of the huA33 antibody may delay the growth of tumor
      cells producing the specific antigen. Oxaliplatin and 5-fluorouracil (5-FU) are cytotoxic
      agents which are considered as standard treatment in metastatic colorectal cancer. Leucovorin
      (folinic acid) is a vitamin which enhances the effect of 5-FU. Eligible patients with
      advanced colorectal cancer will receive huA33 10 mg/m2 by intravenous (IV) infusion weekly
      for twelve weeks. Starting on Study Day 15 (week 3), 5-FU, leucovorin, and oxaliplatin will
      be administered every 2 weeks for 10 weeks. Patients will be evaluated weekly for toxicity.
      Blood samples will be obtained every week for hematology and serum biochemistry analysis and
      for determination of human anti-human antibodies (HAHA). In patients with measurable disease,
      tumors will be assessed by the appropriate scan at baseline and at the end of the thirteen
      week cycle. The primary objective of this study is to assess the safety of huA33 + 5-FU +
      leucovorin + oxaliplatin. The secondary objective is to measure the immunogenicity of huA33
      when given in combination with 5-FU plus leucovorin and oxaliplatin and to document tumor
      responses.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients will be eligible for enrollment if they fulfill all of the following criteria:

          1. Metastatic colorectal cancer.

          2. Histologically or cytologically proven colorectal cancer.

          3. Expected survival of at least 4 months.

          4. Not more than 2 different pretreatment regimens.

          5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

          6. Within the 2 weeks prior to the first dose of huA33, the following vital laboratory
             parameters:

             Lab Parameter Range

               -  Neutrophil count ≥ 1.5 x 10E9/L

               -  Platelet count ≥ 150 x 10E9/L

               -  Serum bilirubin ≤ 2 mg/dL

               -  Creatinine clearance >50 ml/ min

          7. Age ≥ 18 years.

          8. Able and willing to give valid written informed consent.

        Exclusion Criteria:

        Patients will be excluded from the study for any of the following reasons:

          1. Untreated active metastatic disease to the central nervous system defined as new or
             enlarging lesions on CT or MRI.

          2. Surgery or radiotherapy of brain metastases within 3 months prior to the first dose of
             huA33.

          3. Metastatic disease involving > 50% of liver volume.

          4. Other serious illnesses, eg, serious infections requiring antibiotics, bleeding
             disorders.

          5. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing
             (6 weeks for nitrosoureas).

          6. Previous treatment with oxaliplatin.

          7. Previous treatment with huA33 monoclonal antibody or antibody fragment.

             a. Positive huA33 HAHA titer - defined as greater than 3 standard deviations above the
             mean patient normal range by Biacore analysis.

          8. Concomitant treatment with systemic corticosteroids. Topical or inhalational
             corticosteroids are permitted.

          9. Known HIV, Hepatitis B or C positivity.

         10. Mental impairment that may compromise the ability to give informed consent and comply
             with the requirements of the study.

         11. Lack of availability of the patient for clinical and laboratory follow-up assessment.

         12. Participation in any other clinical trial involving another investigational agent
             within 4 weeks prior to first dosing.

         13. Pregnancy or breastfeeding.

         14. Women of childbearing potential: Refusal or inability to use effective means of
             contraception.