| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic Colorectal Cancer |
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| MedDRA Classification |
| 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 |
Evaluate the overall response rate (CR+PR) using RECIST criteria.
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| E.2.2 | Secondary objectives of the trial |
Determine the toxicity profile of Symadex (C-1311);
Determine the time to progression (TTP);
Determine duration of response;
Define the pharmacokinetic and metabolic clearance profile of Symadex (C-1311).
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
a.) 18 years or older;
b.) Histologically confirmed colorectal cancer;
c.) Metastatic colorectal cancer;
d.) Subjects who relapsed after receiving an Oxaliplatin and/or an Irinotecan Regimen, either as adjuvant treatment or as treatment for metastatic disease; if a subject is enrolled directly into the trial following adjuvant therapy, progression to metastatic disease must have occurred > 6 months following completion of adjuvant therapy;
e.) Subjects may have received adjuvant treatment with any regimen prior to initiating treatment for metastatic disease;
f.) Prior chemotherapy treatment must have been terminated at least 3 weeks before the first administration of Symadex (C-1311);
g.) Measurable disease according to RECIST criteria by radiographic methods (CT scan or MRI) and/or clinical examination;
h.) ECOG Performance score less than or equal to 2 with an expected survival of at least 12 weeks;
i.) Adequate renal function as evidenced by the following laboratory tests:
Serum creatinine less than or equal to 1.5 x ULN;
j.) Adequate hepatic function as evidenced by the following laboratory tests:
Serum bilirubin less than or equal to 1.5 x ULN;
Alkaline phosphatase less than or equal to 2.5 x ULN (less than or equal to 5 x ULN, in case of liver metastases);
Serum AST or ALT less than or equal to 2.5 x ULN (less than or equal to 5 x ULN, in case of liver metastases);
k.) Adequate haematologic status as evidenced by the following laboratory tests:
Total WBC greater than or equal to 3.0 x 10^9/L (3,000/mm^3);
Neutrophils greater than or equal to 1.5 x 10^9/L (1,500/mm^3);
Platelets greater than or equal to 100 x 10^9/L (100,000/mm^3);
Haemoglobin greater than or equal to 9.0 g/dL (9g/100 mL);
l.) Negative pregnancy test (urine or blood) and an effective contraception method in women of childbearing potential. Reliable contraception must have been started 4 weeks prior to signing of the informed consent form and must be continued throughout the study and until at least four weeks after completion of study treatment. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. A man participating in this study must utilize reliable contraception for the duration of the study and during 4 weeks afterwards;
m.) Previous radiotherapy is allowed if the end of the treatment was more than 4 weeks prior to the first administration of Symadex (C-1311). Acute radiation toxicities must have resolved. Tumour lesions which are situated in a previously irradiated field will not be considered measurable, unless radiation therapy was completed at least 6 months prior to obtaining screening measurements and the lesion(s) has/have appeared or increased in size since that radiation therapy;
n.) Expected co-operation of the subject for the treatment and follow-up must be obtained and documented;
o.) Written informed consent must be obtained and documented
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| E.4 | Principal exclusion criteria |
a.) Subjects who have received > 2 prior regimens for metastatic colorectal cancer;
b.) Myocardial infarction within 3 months of signature of the informed consent;
c.) Unstable angina pectoris, cardiac insufficiency (NYHA Class III-IV), uncontrolled arrhythmia, or uncontrolled hypertension at the time of signature of the consent form;
d.) Left Ventricular Ejection Fraction (LVEF) < 50% or below institutional limit of normal;
e.) Absolute QTc interval > 450 msec
f.) Pre-existing neuropathy (motor or sensory) > grade 2;
g.) Clinically significant abnormal haematological parameters other than those defined in the inclusion criteria;
h.) Clinically significant abnormal biochemical parameters other than those defined in the inclusion criteria;
i.) Prior major surgery less than 4 weeks before the first administration of Symadex (C-1311). Subject must have recovered from prior surgery;
j.) Subjects who received treatment with myeloid growth factors (i.e. G-CSF, GM-CSF) or blood transfusion within 2 weeks of obtaining the screening haematological blood work;
k.) Pregnant or lactating women;
l.) Clinically significant active infections;
m.) Other prior malignancies, except for cured non melanoma skin cancer or curatively treated in situ carcinoma of the cervix or adequately treated malignancies for which there has been no evidence of activity for more than 5 years;
n.) Other serious illness or medical condition;
o.) Subjects with a history of a mental illness or condition which may interfere with the subjects’ ability to understand the requirements of the study;
p.) Subjects who received an investigational new drug within 4 weeks of the first administration of Symadex (C-1311);
q.) Any other known condition which in the investigator’s opinion would not make the subject a good candidate for the trial;
r.) Known HIV positive or active hepatitis B or C. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary:
Overall response rate (ORR) = complete response (CR) + partial response (PR) using RECIST criteria.
Secondary:
Time to progression (TTP) and duration of response.
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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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| 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 | No |
| E.8.1.1 | Randomised | No |
| 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 | No |
| 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) | No |
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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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| The end of the trial refers to the completion of the active phase of the study i.e. from the first does to the end of the safety follow up. |
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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 | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
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