Capecitabine and 131I-huA33 in Patients With Metastatic Colorectal Cancer
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms
Intervention: Capecitabine; 131I-huA33 (131-Iodine on humanised monoclonal antibody A33)
Intervention description: Capecitabine was administered orally at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle. Daily doses were rounded to the nearest 150 mg.; All patients received a dose of 5 mg huA33 conjugated to 5-8 mCi 131I. The therapy dose of 131I-huA33 comprised a constant protein dose of 10 mg/m2 huA33 regardless of dose level. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I).
Intervention MeSH terms: Capecitabine; Antibodies; Antibodies, Monoclonal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this clinical trial is to determine whether it is safe to treat patients with
      advanced colorectal cancer, with humanised A33 antibody tagged with radioactive iodine
      (131I-huA33) in combination with chemotherapy (capecitabine).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Metastatic colorectal cancer.

          -  Histologically or cytologically proven colorectal cancer.

          -  Measurable disease on CT scan with at least one lesion >/= 2cm diameter (to allow
             adequate infusion imaging).

          -  Expected survival of at least 4 months.

          -  ECOG performance status 0-2.

          -  Vital laboratory parameters should be within normal range including:

               1. Neutrophils >/= 1.5 x 10^9/L;

               2. Platelets >/= 150 x 10^9/L;

               3. Serum bilirubin </= 34 micromol/L;

               4. Calculated creatinine clearance > 50 ml/min.

          -  Age >/= 18 years.

          -  Able and willing to give valid written informed consent.

        Exclusion Criteria:

          -  Previous treatment with capecitabine.

          -  Untreated active metastatic disease to the central nervous system (new or enlarging
             lesions on CT or MRI), or within 3 months of treatment (ie surgery or radiotherapy)
             for brain metastases.

          -  Other serious illnesses, eg, serious infections requiring antibiotics, bleeding
             disorders.

          -  Liver involvement with metastatic disease > 50% liver volume.

          -  Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6
             weeks for nitrosoureas).

          -  Previous external beam irradiation except if: (i) it was for standard adjuvant pelvic
             radiation for rectal cancer; (ii) it was for localised irradiation for skin cancer; or
             (iii) the sum total of all previous external beam irradiation port areas is not
             greater than 25% of the total red marrow.

          -  Previous treatment with a monoclonal antibody or antibody fragment AND a positive
             huA33 human anti-human antibody (HAHA) titre.

          -  Concomitant treatment with systemic corticosteroids. Topical or inhalational
             corticosteroids are permitted.

          -  Mental impairment that may compromise the ability to give informed consent and comply
             with the requirements of the study.

          -  Lack of availability of the patient for clinical and laboratory follow-up assessment.

          -  Participation in any other clinical trial involving another investigational agent
             within 4 weeks prior to enrollment.

          -  Pregnancy or breastfeeding.

          -  Women of childbearing potential: Refusal or inability to use effective means of
             contraception.