Second-line therapy for previously-treated advanced or metastatic colorectal adenocarcinoma MedDRA version: 9.1 Level: LLT Classification code 10052360 Term: Colorectal adenocarcinoma
Conditions
Interventions
Product Name: CS-1008
Product Code: CS-1008
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: tigatuzamab
Current Sponsor code: CS-1008
Concentration unit: mg/ml milligram(s)/
Sponsors
Daiichi Sankyo Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed CRC which is now metastatic and after failure of oxaliplatin-based first-line treatment. Failure of oxaliplatin-based therapy includes subjects who have progressed during oxaliplatin-based treatment and those that have progressed within 6 months of an oxaliplatin-induced response (progression being defined as RECIST measurements returning to baseline measurements). Subjects who have relapsed within 6 months of an oxaliplatin-based adjuvant regimen can also be considered for inclusion in the study. 2. At least 18 years of age. 3. Eastern Cooperative Oncology Group (ECOG) performance status = 1. 4. Measurable disease based on RECIST criteria. 5. Adequate organ and bone marrow function as evidenced by: - Hemoglobin = 9.0 g/dL (may be transfused to this level); - Absolute neutrophil count (ANC) = 1.5 x 10e+9/L; - Platelet count = 100 x 10e+9/L; - Serum creatinine = upper limit of normal (ULN) or creatinine clearance > 50 mL/min; - AST = 2.5 x ULN in subjects with no liver metastasis and = 5.0 x ULN in subjects with liver metastasis; - Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Anticipation of need for a major surgical procedure or radiotherapy (RT) during the study. 2. Treatment with chemotherapy hormonal therapy, RT, minor surgery, or any investigational agent within 4 weeks before study enrollment. Treatment with nitrosoureas, mitomycin C, immunotherapy, biological therapy, or major surgery within six weeks prior to study enrollment. St John’s Wort within 2 weeks prior to study enrollment or during the study. 3. History of any of the following conditions within 6 months before study enrollment: Clinically significant myocardial infarction or severe/unstable angina pectoris; New York Heart Association (NYHA) class III or IV congestive heart failure; Clinically significant cerebrovascular accident, transient ischemic attack or pulmonary embolism; Clinically significant pulmonary disease (e.g., severe chronic obstructive pulmonary disease or asthma) 4. Presence of any of the following: Symptomatic brain metastasis; an uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis. 5. Clinically significant active infection that requires antibiotic therapy or Human Immunodeficiency Virus (HIV) positive subjects receiving antiretroviral therapy. 6. History of malignancy other than CRC, unless there is the expectation that the malignancy has been cured, and tumor specific treatment for the malignancy has not been administered within the previous 5 years. Exceptions to this are non melanotic cancer of the skin and adequately treated carcinoma of the cervix-in-situ. 7. Previous treatment with CS-1008, other agonistic DR5 antibody agents, or tumor necrosis factor (TNF)-related apoptosis inducing ligand TRAIL agents. 8. History of active chronic inflammatory bowel disease and/or bowel obstruction within the last 3 months. 9. Pregnant or breast feeding. 10. Known history of hypersensitivity reactions to irinotecan or to one of the excipients. 11. Serious intercurrent medical or psychiatric illnesses or any other conditions that in the opinion of the Investigator would impair the ability to give informed consent or unacceptably reduce protocol compliance or safety of the study treatment. 12. Known Gilbert’s disease. 13. More than 50% of the liver replaced by tumor. 14. Homozygous for UGT1A1*28.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to estimate the difference in treatment effect between CS-1008 administered in combination with irinotecan and irinotecan alone, as measured by progression-free survival (PFS).;Secondary Objective: Secondary objectives are to determine: - Overall and median survival, - Objective response rate (ORR) (i.e, complete response [CR] and partial response [PR] rate), - Safety and tolerability of CS-1008 administered in combination with irinotecan - Incidence of anti-CS-1008 antibody formation, - To evaluate serum levels of CS-1008 at the scheduled time points. ;Primary end point(s): The primary efficacy endpoint is Progression-Free Survival (PFS) | — |
Countries
United Kingdom
Outcome results
None listed