Phase I Trial of huA33 Plus Chemotherapy in Patients With Metastatic Colorectal Cancer
Colorectal Cancer
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring Colorectal Cancer, huA33, antibody, chemotherapy
Eligibility Criteria
Inclusion Criteria: Patients will be eligible for enrollment if they fulfill all of the following criteria: Metastatic colorectal cancer. Histologically or cytologically proven colorectal cancer. Expected survival of at least 4 months. Not more than 2 different pretreatment regimens. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 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 Age ≥ 18 years. Able and willing to give valid written informed consent. Exclusion Criteria: Patients will be excluded from the study for any of the following reasons: Untreated active metastatic disease to the central nervous system defined as new or enlarging lesions on CT or MRI. Surgery or radiotherapy of brain metastases within 3 months prior to the first dose of huA33. Metastatic disease involving > 50% of liver volume. Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing (6 weeks for nitrosoureas). Previous treatment with oxaliplatin. 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. Concomitant treatment with systemic corticosteroids. Topical or inhalational corticosteroids are permitted. Known HIV, Hepatitis B or C positivity. 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 first dosing. Pregnancy or breastfeeding. Women of childbearing potential: Refusal or inability to use effective means of contraception.
Sites / Locations
- Krankenhaus Nordwest
- UniversitaetsSpital Zuerich
Arms of the Study
Arm 1
Experimental
huA33 antibody plus chemotherapy
huA33 was administered intravenously over a period of 30 minutes once a week at a dose of 10 mg/m2 for 12 weeks. Starting on day 15 and continuing every second week, oxaliplatin, 5-fluorouracil (5-FU) and leucovorin were also administered. Oxaliplatin and leucovorin were given as infusions over 2 hours. Afterwards, patients received a bolus infusion of 5-FU intravenously followed by an infusion of 5-FU over 22 hours. The doses of oxaliplatin were 85mg/m2, leucovorin 200mg/m2, 400mg/m2 of 5-FU as a bolus infusion and 600mg/m2 as a continuous infusion. A complete treatment cycle consisted of 12 weeks. Patients were eligible to receive an additional cycle in the absence of dose-limiting toxicity (DLT), immunogenicity (huA33 human anti-human antibodies {HAHA}) and disease progression.