E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage III and IV Colorectal Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of the colon and rectum (colorectal cancer) can invade and damage tissues and organs. Tumors of the colon/ rectum are growths of the inner wall of the large intestine. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010034 |
E.1.2 | Term | Colorectal cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010035 |
E.1.2 | Term | Colorectal cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 is to compare the progression free survival (PFS) rate of colorectal cancer patients treated with CS-7017 or placebo at 18 weeks in patients who have achieved a response of disease control (complete response [CR],partial response [PR] or stable disease [SD]) to standard first line therapy. |
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E.2.2 | Secondary objectives of the trial |
1/ Compare the overall PFS and overall survival (OS) of patients treated with CS-7017 or placebo and
2/ Compare the safety parameters of patients treated with CS-7017 or placebo
3/ Pharmacokinetic Objectives:
The pharmacokinetic objective is to analyse the population PK of CS-7017.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with histologically-confirmed, metastatic or locally advanced CRC
(stages III or IV) and must have received standard first line combination
chemotherapy:
a) Patients must receive their primary treatment until best response (disease control) has been reached, i.e., CR, PR or SD as determined by the Investigator;
b) Patients must enter the trial within 8 weeks after completing first line therapy;
c) Standard first line combination chemotherapy can consist of a fluoropyrimidine
based regimen:
i) FOLFOX (folinic acid + fluoropyrimidine + oxaliplatin); or
ii) FOLFIRI (folinic acid + fluoropyrimidine + Irinotecan); or
iii) Other fluoropyrimidine based regimens, e.g., XELOX (capecitabine +
oxaliplatin) and the use of a fluoropyrimidine based regimen;
iv) Also, a biological adjunct such as bevacizumab is allowed in combination
with such fluoropyrimidine based regimens;
2. A minimum of one unidimensionally-measurable target lesion according to
RECIST (Response Evaluation Criteria in Solid Tumors, Version 1.0);20, unless
CR was achieved;
3. Age ≥ 18 years and Eastern Cooperative Oncology Group (ECOG) performance
status ≤ 2 at study entry;
4. Resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE,
Version 3.0, grade ≤ 1;
5. Adequate organ and bone marrow function as evidenced by:
· Haemoglobin ≥ 10 g/dL (transfusion and/or growth factor support allowed);
· Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;
· Platelet count ≥ 100 x 109/L;
· Serum creatinine ≤ 1.5 x ULN or creatinine clearance >60 mL/min;
· AST and alkaline phosphatase <2.5 x ULN if without liver metastasis and ≤
5.0 x ULN if liver metastasis;
· Total bilirubin ≤ 2.0 x ULN;
· Prothrombin time (PT)/International Normalised Ratio (INR) within normal
limits (WNL) unless therapeutically anticoagulated;
6. Women of childbearing potential and men must be willing to consent to using
highly effective methods of contraception (eg, hormonal contraceptives, bilateral
tubal ligation, barrier with spermicide, intrauterine device) while on treatment and
for at least 3 months thereafter;
7. Males with the potential to father children and women of childbearing
potential must use two of the following methods of contraception acceptable for
the study (e.g. hormonal contraceptives, bilateral tubal ligation, barrier with
spermicide, intrauterine device) while on trial treatment and for at least 3 months
thereafter;
8. All female subjects of childbearing potential must have a negative pregnancy test
(serum or urine) result within 7 days before initiating study treatment;
9. Baseline laboratory tests must have been performed within 2 weeks before
initiating study treatment and baseline tumour assessment must have been
performed within 28 days before initiating study treatment;
10. Subjects must be fully informed about their illness and the investigational nature
of the study protocol (including foreseeable risks and possible side effects) and
must sign and date an IEC-approved ICF before performance of any
study-specific procedures or tests.
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E.4 | Principal exclusion criteria |
1. Anticipation of need for a major surgical procedure or radio therapy during the study;
2. Treatment for cancer with chemotherapy, hormonal therapy, minor surgery, or any investigational agent within 4 weeks before study enrolment. Treatment with immunotherapy, biological therapy, or major surgery within 6 weeks before study enrolment. Treatment with RT within 1 week before study enrolment.
3. History of any of the following conditions: diabetes mellitus requiring treatment with insulin or oral agents, malabsorption syndrome, chronic diarrhoea (lasting ≥4 weeks duration), inflammatory bowel disease, or partial bowel obstruction;
4. Concomitant use of other TZDs;
5. Any of the following clinically significant conditions within 6 months before enrolment: myocardial infarction, NYHA Class II or higher severe/unstable angina pectoris (See Section 17.2), coronary/peripheral artery bypass graft; congestive heart failure; cerebrovascular accident or transient ischemic attack, pulmonary embolism, or other clinically significant thromboembolic event; clinically significant pulmonary disease (e.g., severe COPD or severe asthma); clinically significant pulmonary oedema;
6. Brain metastasis; an uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis;
7. Clinically significant pleural or pericardial effusion. Subjects with minimal pleural effusion may be eligible upon request by Investigator and approval by Sponsor;
8. Clinically significant active infection that requires antibiotic therapy or Human Immunodeficiency Virus (HIV) positive subjects receiving antiretroviral therapy;
9. Pregnant or breast feeding;
10. Known history of severe hypersensitivity reactions to any of the components of CS 7017 formulations;
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;
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study is the rate of progression free survival (PFS) at 18 weeks. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary endpoints for this study are PFS and overall survival and safety endpoints (ie, AEs and clinical laboratory evaluations). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Czech Republic |
France |
Germany |
Italy |
Poland |
Russian Federation |
Spain |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 clinical end of trial will be defined as the date of the last subject's follow up visit |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |