A Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer

• Status: Completed
• Trial end date: 2012-06-27
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ludwig Institute for Cancer Research
• Collaborators: Daiichi Sankyo Inc.; Daiichi Sankyo, Inc.

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.