E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Second-line therapy for previously-treated advanced or metastatic colorectal adenocarcinoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052360 |
E.1.2 | Term | Colorectal adenocarcinoma |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 < 1.5 x ULN
6. Women of childbearing potential must be willing to consent to using effective contraception (e.g., hormonal contraceptives, bilateral tubal ligation, barrier with spermicide, intrauterine device) while on treatment and for 3 months thereafter.
7. All female subjects of childbearing potential must have a negative pregnancy test (serum or urine) result within 14 days before initiating study treatment.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is Progression-Free Survival (PFS) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |