E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage III colon adenocarcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Stage III colon adenocarcinoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
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 |
Examine the predictive value of PET-assessed tumour FDG uptake response after one course of preoperative chemotherapy on the outcome of adjuvant therapy, measured by 3-year DFS. |
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E.2.2 | Secondary objectives of the trial |
1. Examine the predictive value of PET-assessed tumour FDG uptake changes after one course of preoperative chemotherapy on OS
2. Evaluate the best cut-off value for relative delta SUV in assessment of preoperative chemotherapy response by FDG-PET/CT imaging.
3. Analyze the cost-effectiveness of preoperative chemo-sensitivity testing
Translational research:
4. Assess the predictive value of SNPs on toxicity- and drug target-related genes on DFS
5. To assess genomic rearrangements associated with response or resistance to FOLFOX treatment
6. To identify an immunologic signature associated with metabolic tumour response to FOLFOX therapy
7. Create a frozen tumour bank for future studies |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
* Age 18 years or older
* Clinical/radiological evaluation compatible with stage III colon adenocarcinoma
*No prior chemotherapy
* No prior abdominal or pelvic irradiation
*WHO performance status 0 or 1
*Effective contraception during the study and the following six months
*Signed informed consent obtained prior to any study-specific screening procedures
*Tumour considered as curatively resectable (R0) based on standard preoperative evaluations
*White blood cell count ≥ 3×109/L with neutrophils ≥ 1.5×109/L, platelet count ≥ 100×109/L, haemoglobin ≥ 9 g/dL (5.6 mmol/L)
*Direct bilirubin ≤ 1.5×ULN; ASAT and ALAT ≤ 2.5×ULN; Alkaline phosphatase ≤ 2.5×ULN; Serum creatinine ≤ 1.5×ULN |
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E.4 | Principal exclusion criteria |
*Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to screening. Incompletely healed wounds or anticipation of the need for major surgical procedure during the course of the study
*Any suspicion of metastatic disease
*Rectal cancer located within 15 cm from the anal verge by endoscopy or under the peritoneal reflection at surgery
*Inflammatory bowel disease
*Pregnancy (absence to be confirmed by ß-hCG blood test) or breast-feeding
*History or current central nervous system disease or peripheral neuropathy
*Hypersensitivity to any of the components of study treatments
* Previous malignancy in the last five years except basal-cell carcinoma of the skin or in situ cervical carcinoma
*Clinically relevant coronary artery disease or history of myocardial infarction in the last 6 weeks or high risk of uncontrolled arrhythmia
*Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent
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E.5 End points |
E.5.1 | Primary end point(s) |
Examine the predictive value of PET-assessed tumour FDG uptake response after one course of preoperative chemotherapy on the outcome of adjuvant therapy, measured by 3-year DFS. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Examine the predictive value of PET-assessed tumour FDG uptake changes after one course of preoperative chemotherapy on OS
2. Evaluate the best cut-off value for relative delta SUV in assessment of preoperative chemotherapy response by FDG-PET/CT imaging.
3. Analyze the cost-effectiveness of preoperative chemo-sensitivity testing
Translational research:
4. Assess the predictive value of SNPs on toxicity- and drug target-related genes on DFS
5. To assess genomic rearrangements associated with response or resistance to FOLFOX treatment
6. To identify an immunologic signature associated with metabolic tumour response to FOLFOX therapy
7. Create a frozen tumour bank for future studies |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Examine the predictive value of PET-assessed tumour FDG uptake changes after one course of preoperative chemotherapy on OS
2. Evaluate the best cut-off value for relative delta SUV in assessment of preoperative chemotherapy response by FDG-PET/CT imaging.
3. Analyze the cost-effectiveness of preoperative chemo-sensitivity testing
Translational research:
4. Assess the predictive value of SNPs on toxicity- and drug target-related genes on DFS
5. To assess genomic rearrangements associated with response or resistance to FOLFOX treatment
6. To identify an immunologic signature associated with metabolic tumour response to FOLFOX therapy
7. Create a frozen tumour bank for future studies |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
prognostic and predictive |
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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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 26 |
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 | No |
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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‐ when the required number of progression events is reached
‐ The database has been fully cleaned and frozen for the primary analysis and for the analysis of the secondary endpoints
‐ Or, if the number of events is not reached and a decision to stop accrual has been taken by the principal investigator.
‐ Participants will be followed until one of the following criteria applies:
Participant decides to withdraw from the study.
Participant is lost to follow‐up.
Death |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |