A Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms
Intervention: CS-1008
Intervention description: CS-1008 was administered once weekly as an intravenous infusion over 30 ± 10 minutes at a dose range of 0.2 to 6 mg/kg. On Days 1 and 36, CS-1008 infusions were radiolabeled with 111^In (5-7 mCi).
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Clinical trial; CS-1008 mAb; monoclonal antibody CS-1008; Positron-Emission Tomography; Pharmacokinetics; Pharmacodynamics; apoptosis; caspases

Summary:

      This was a Phase 1, open-label, single-center study of CS-1008, an immunoglobulin G subclass
      1 (IgG1) humanized monoclonal antibody, in subjects with advanced colorectal carcinoma who
      had received ≥ 1 prior chemotherapy regimen for metastatic disease. Primary study objectives
      were to determine the influence of the CS-1008 dose on the biodistribution, pharmacokinetics
      (PK) and tumor uptake of radiolabeled CS-1008 following a single infusion and following
      continuous sequential doses of CS-1008. Secondary objectives were to evaluate changes in
      tumor metabolism, antitumor response, and changes in serum apoptosis biomarkers and tumor
      response markers following treatment with CS-1008.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically proven metastatic colorectal cancer with 1 target lesion ≥ 2 cm and
             evaluable by gamma camera imaging. If this lesion was previously irradiated,
             progression must have been documented following radiotherapy.

          2. Received at least 1 prior course of chemotherapy for metastatic disease.

          3. Expected survival of at least 3 months.

          4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

          5. Age ≥ 18 years old.

          6. Able and willing to give valid written informed consent.

          7. Within the last 1 week prior to first study drug administration, laboratory parameters
             for vital functions were to be in the normal range. Laboratory abnormalities that were
             not clinically significant were generally permitted, except for the following
             laboratory parameters, which were to be within the ranges specified:

               -  Neutrophil count: ≥ 1.5 x 10^9/L

               -  Platelet count: ≥ 90 x 10^9/L

               -  International normalized ratio: ≤ 1.5

               -  Serum bilirubin: ≤ 1.5 x upper limit of normal (ULN)

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤ 2 x ULN (≤
                  5 x ULN if liver metastases)

               -  Calculated creatinine clearance (Cockcroft-Gault formula): ≥ 55 mL/min

        Exclusion Criteria:

          1. Active central nervous system metastases. Definitively treated metastases were allowed
             if stable for 6 weeks off therapy.

          2. Known immunodeficiency or human immunodeficiency virus positivity.

          3. Serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders,
             or any condition that in the opinion of the Investigator would have interfered with
             the ability of the subject to fulfill the study requirements.

          4. Other malignancy, apart from non-melanoma skin cancer, within 3 years prior to first
             study drug administration, that in the opinion of the Investigator had >10% risk of
             relapse within 12 months.

          5. Chemotherapy, radiotherapy, or investigational agent within 4 weeks prior to first
             study drug administration.

          6. Regular corticosteroid, nonsteroidal anti-inflammatory drug (NSAID) (other than
             paracetamol or low-dose aspirin) or other immunosuppressive treatment within 3 weeks
             prior to first drug administration. Intermittent dosing of corticosteroid or NSAID was
             permitted if less than 4 doses within a 3-day period.

          7. Mental impairment that may have compromised the ability to give informed consent and
             comply with the requirements of the study.

          8. Lack of availability for clinical follow-up assessments.

          9. Pregnancy or breastfeeding.

         10. Women of childbearing potential: refusal or inability to use effective means of
             contraception.